PhD Projects

Our researchers belong to one of four research centres that investigate problems using different approaches. Many of our projects are cross-disciplinary, with advisors from different centres, giving you the benefit of a wider range of expertise.

Our PhD projects are divided into 'Global Challenges PhD Projects', 'Standard PhD Projects' and 'Earmarked PhD Projects'. Where available, please select a Centre to explore all available PhD projects in that category. For any queries, please contact the HDR Liaison Officer, hdr.imb@enquire.uq.edu.au.

Research Groups PhD Homepage

Global Challenges PhD Projects

The Global Challenges top-up only applies to Global Challenges PhD Projects (listed here). It is a $5,000 top up to the UQ Graduate School Scholarship plus $5,000 support for a placement and $2,000 professional development support (over the period of the candidature) to outstanding domestic and eligible international onshore applicants. For more information on the scholarship top up please visit the UQ Graduate website. The theme for Global Challenges PhD projects commencing in RQ1, 2025 is 'Drugs inspired by nature'. Please note, applications are now closed.

Characterisation of blood-brain barrier nutrient transporters

Principal Advisor: Dr Rosemary Cater (r.cater@uq.edu.au)

Associate Advisor: Dr Anne Lagendijk (a.lagendijk@imb.uq.edu.au)

The blood-brain barrier (BBB) is a layer of tightly packed endothelial cells that separate the blood for the brain. The BBB has evolved to protect our brains from blood-borne neurotoxins and pathogens, but unfortunately, it also prevents the majority of potential neurotherapeutics from entering the brain. In fact, it has been estimated that ~98% of all small-molecule drugs are not able to cross the BBB. This creates a major bottleneck in the development of treatments for diseases such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, anxiety, and depression. The more we know about what can enter the brain, the better informed we will be for developing treatments for these diseases. Transporter proteins expressed at the BBB play a very important role in regulating the entrance of molecules in a highly specific manner. For example, the transporters FLVCR2 and MFSD2A allow for the uptake of choline and omega-3 fatty acids into the brain – both of which are essential nutrients that the brain requires in very large amounts. This project will utilise biochemical techniques and structural biology (cryo-EM) to further understand transport proteins at the BBB and how they transport specific molecules into the brain. This will provide critical insights that for the development of neurotherapeutics that can hijack these transporters to allow for entrance into the brain.

Chemical embedding in artificial intelligence models

Principal Advisor: Dr Johannes Zuegg (j.zuegg@imb.uq.edu.au)

Associate Advisor: TBC

The embedding of chemical structures for deep learning network is currently limited to a few approaches that fail to represent the chemical properties in an efficient and comprehensive way. Especially for large language models the embedding of chemical information is limited to methods containing few chemical properties, or associated biological activities in the case of bioactive chemicals. The project will explore and develop embedding methods that can enrich chemical and biological properties, using chemical relevant transformations to provide enriched descriptors. The project will explore their application in predictive and generative models, able to generate new chemical structures with a desired biological activity. The project has thereby access to the existing large of the Community for Open Antimicrobial Drug Discovery (CO-ADD), which has collected the structures and biological activity of over 500,000 chemicals.

Designing mini-protein chaperones for dementia treatment

Principal Advisor: Dr Michael Healy (michael.healy@uq.edu.au)

Associate Advisor: Professor Brett Collins (b.collins@imb.uq.edu.au)

At the heart of neurodegeneration is the concept of proteostasis, the tight regulation of protein synthesis, transport, degradation, and recycling. Defective proteostasis results in the toxic accumulation of proteins and peptides such as amyloid β (Aβ) and phosphorylated tau. The major pathway that regulates proteostasis is the sorting and degradation of transmembrane proteins in the endolysosomal system, and associated autophagic and lysosomal destruction of toxic cytosolic molecules. Retromer is a trimeric protein complex that is a central player in regulating the endolysosomal system and is downregulated in the hippocampus of patients with Alzheimer’s disease. Molecules (termed molecular chaperones) that stabilise this complex increase Retromer levels in neurons and decrease levels of neurotoxic Aβ, however, to date no molecule has made it into the clinic. Here I will use our knowledge of fundamental Retromer biology to design a suite of ‘mini-protein’ molecular chaperones using revolutionary machine learning techniques (Alphafold, RFdiffusion) and test their ability to stabilise Retromer in vitro and reverse dysfunction in known cellular models of neurodegeneration. Unlike traditional drug screening approaches, these revolutionary techniques allow for the generation of novel protein backbones that bind to specified regions of a protein or protein complex. If successful, these molecular chaperones could represent novel therapeutics for the treatment of the underlying molecular pathology that is common in neurodegeneration.

Developing ionobiotics for the targeted treatment of multi-drug resistant bacteria

Principal Advisor: Professor Mark Walker (mark.walker@uq.edu.au)

Associate Advisor: Dr David De Oliveira (d.deoliveira@uq.edu.au) and Proessor Maree Smith (SBMS; maree.smith@uq.edu.au)

Antimicrobial resistance (AMR) is a growing source of morbidity, mortality, and economic and health-care costs. The innovative use of ionophores to break antibiotic resistance in clinically relevant multidrug-resistant bacteria has paved a therapeutic pathway to investigate ionophores as direct-acting antibiotics. By utilising a validated drug development program, this project will define the utility of these promising new compounds by exploring their mode of action, the range of pathogens that can be treated, and their drug pharmacology profiles during infection. Ionophores represent a NEW-CLASS of antibiotics with broad-spectrum activity against a wide range of antimicrobial-resistant bacterial species. Our overarching goal is to expand the repertoire of effective antibiotic therapies available for AMR associated infections.

Development of venom-derived blood-brain barrier shuttles

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: A/Prof Johan Rosengren (UQ School of Biomedical Sciences)

The blood-brain barrier controls the transfer of substances between the blood and the brain, protecting us from toxic compounds while allowing the transfer of nutrients and other beneficial molecules. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. The project will involve cell culture, blood-brain barrier assays, proteomics, peptide chemistry, NMR structure determination, and molecular biology and pharmacology. The candidate should have a degree in biochemistry, pharmacology or cell biology, good hands-on laboratory skills and strong ambition and work ethics. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovative discovery and chemistry strategies to advance fundamental research across the chemical and biological sciences.

Exploring Australian Microbes for Next-Generation Medicines through Soils for Science (S4S)

Principal Advisor: Dr Zeinab Khalil (z.khalil@uq.edu.au)

Associate Advisor: Dr Angela Salim (a.salim@imb.uq.edu.au), Professor Rob Capon (r.capon@imb.uq.edu.au) and A/Prof Loic Yengo (l.yengo@imb.uq.edu.au)

Microbes have been a new promising source of modern medicines, including antibiotics (e.g. penicillin) and immunosuppressants (e.g. sirolimus) and well as agents to treat cancer (e.g. adriamycin) and cardiovascular (e.g. statins) disease, as well as many more. Recent advances in genomics offer the prospect of exciting new approaches to discovering the next generation of medicines hidden within the Australian microbiome.

This project will annotate the S4S microbe library to prioritize those that are genetically and chemically unique. These will be subjected to cultivation profiling, and fermentation, followed by chemical analysis to isolate, identify and evaluate new classes of chemical diversity.

The successful candidate will join a multi-disciplinary team where, supported by microbiological and genomic sciences, they will gain skills and experience in analytical, spectroscopic and medicinal chemistry – to inform and inspire the discovery of future medicines.

Applicants must have a strong background with outstanding grades in organic chemistry, and with an interest in learning multidisciplinary biosciences.

From Bugs to Drugs: Improving drug delivery into cancer and immune cells.

Principal Advisor: Professor Jennifer Stow (j.stow@imb.uq.edu.au)

Associate Advisor: Professor Mark Schembri (m.schembri@uq.edu.au) and Professor Halina Rubinsztein-Dunlop (SMP; halina@physcics.uq.edu.au)

The efficient delivery of drugs, vaccines, mRNAs and nanoparticles into human cells is still a major challenge for treating and preventing disease. Bugs, or bacteria, hold the key for penetrating our cells by hijacking endocytic, phagocytic and other trafficking pathways with their effector proteins. We can use these effectors too, to develop new methods for penetrating cancer cells and immune cells to improve drug delivery and to manipulate cell function and survival. Our bug-based effectors will be made, tagged and used for microscopy and live imaging of cells and for measuring biophysical properties of the cell membranes. We will explore effector-enhanced drug delivery and monitor disease processes in organoids and live tissues, in collaboration with microbiologists, physicists, immunologists and clinicians.

How E. coli cause urinary tract infections

Principal Advisor: Professor Mark Schembri (m.schembri@uq.edu.au)

Associate Advisors: Professor Matthew Sweet (m.sweet@imb.uq.edu.au)

Urinary tract infections (UTIs) are one of the most common infectious diseases, with a global annual incidence of approximately 400 million cases. UTI is also a major precursor to sepsis, which affects about 50 million people worldwide each year, with a mortality rate of 20-40% in developed countries. Uropathogenic E. coli (UPEC) is the major cause of UTI and a leading cause of sepsis, and associated with high rates of antibiotic resistance. This project will explore how UPEC cause disease, with a goal to identify new approaches to treat and prevent infection. Students with an interest in microbiology, bacterial pathogenesis, animal infection models and antibiotic resistance are encouraged to apply.

Investigating the therapeutic potential of the trefoil factor family for treating gastrointestinal disorders.

Principal Advisor: A/Prof Markus Muttenthaler (m.muttenthaler@imb.uq.edu.au)

Associate Advisor: A/Prof Johan Rosengren (UQ School of Biomedical Sciences; j.rosengren@uq.edu.au)

Inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS) affect 10–15% of the population, having a substantial socio-economic impact on our society. The aetiology of these disorders remains unclear, and treatments focus primarily on symptoms rather than the underlying causes.

Our research group is pursuing innovative therapeutic strategies targeting gastrointestinal wound healing and protection to reduce and prevent such chronic gastrointestinal disorders. This project focuses on the trefoil factor family, an intriguing class of endogenous gut peptides and key regulators for gastrointestinal homeostasis and protection. The project will focus on the chemical synthesis of the individual members and molecular probe and therapeutic lead development to advance our understanding of their mechanism of action and explore the therapeutic potential of these peptides for treating or preventing gastrointestinal disorders.

The candidate should have a degree in chemistry, biochemistry, pharmacology or cell biology, good hands-on laboratory skills, and strong ambition and work ethics. The candidate will be involved in solid-phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, NMR, cell culture, wound healing assays, gut stability assays, cell signalling and receptor pharmacology.

Mapping chemical diversity in Australian marine microbes

Principal Advisor: Dr Zeinab Khalil (z.khalil@uq.edu.au)

Associate Advisor: Dr Angela Salim (a.salim@imb.uq.edu.au), Professor Rob Capon (r.capon@imb.uq.edu.au) and Dr Mariusz Skwarczynski (SCMB)

There are multiple reasons why the discovery and development of new marine bioproducts is highly dependent on a quantitative understanding (mapping) of the chemical diversity intrinsic to different Australian marine biomass.

Firstly, the informed selection of marine biomass strains to support commercial production is greatly enhanced by knowledge of the yield, structures and diversity of small molecule and peptide bioactives – especially where these are the active agents critical to product properties (ie human health immunomodulatory, anti-infective, cardioprotective, neuroprotective and antioxidants; animal health antiparasitics; crop protection fungicides, herbicides and insecticides; livestock/crop productivity grow promoters; and/or new fine chemical pigments or flavouring agents).

Secondly, knowledge of chemical diversity and bioactives can significantly advance the design of optimal methods for production, harvest, handling, biorefining, biomanufacturer and product formulation, inclusive of quality control to monitor bioactive recovery, stability and content at each stage of the production cycle.

Thirdly, knowledge of chemical diversity can be used to improve the utilisation of biomass, and increase commercial returns, by identifying additional product classes from a single biomass. For example, analysis of biorefinery fractions after recovery of a primary marine bioproduct (ie omega-3-fatty acids or fucoidan) could reveal new product classes – with application inclusive of new functional foods and feeds, nutriceuticals, therapeutics, livestock and crop agrochemicals, and more.

This project seeks to develop advanced and optimised methods in UPLC-QTOF-MS/MS molecular networking, to rapidly, cost effectively, reproducibly and quantitatively map the small molecule and peptide chemical diversity of taxonomically and geographically diverse Australian marine microbes and microalgae, including fresh and processed biomass, biorefinery fractions and outputs, and formulated marine bioproducts – to advance the discovery and development of valuable new marine bioproducts.

Applicants must have a strong background with outstanding grades in organic chemistry, and with an interest in learning multidisciplinary biosciences.

Medicinal chemistry strategies to remove bacterial biofilms associated with gastrointestinal disorders

Principal Advisor: A/Prof Markus Muttenthaler (m.muttenthaler@imb.uq.edu.au)

Associate Advisor: Professor Mark Blaskovich (m.blaskovich@imb.uq.edu.au)

Gastrointestinal disorders such as irritable bowel disorders (IBS) and inflammatory bowel diseases (IBD) affect 10–15% of the population, reduce the quality of life of millions of individuals, and result in substantial socioeconomic costs. Recently, we revealed a high prevalence of macroscopically visible bacterial biofilms in the gastrointestinal tracts of IBD and IBS patients, linking these biofilms to a dysbiosis of the microbiome and the pathologies. Using patient-derived biofilm-producing bacterial strains, we established biofilm bioassays and identified leads capable of removing these biofilms.

This project pursues cutting-edge medicinal chemistry strategies to advance various lead molecules towards drug candidates and enhance their therapeutic window and biofilm-specificity. Techniques that will be acquired include: solid-phase peptide synthesis, organic chemistry, medicinal chemistry, high-performance liquid chromatography, mass spectrometry, proteomics, nuclear magnetic resonance spectroscopy, gut stability assays, and antimicrobial and biofilm assays.

The candidate should have a degree in chemistry, biochemistry or pharmacology, good hands-on laboratory skills, and a desire to drive the project. The candidate will be involved in solid-phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, gut stability assays, and antimicrobial, antibiofilm and cytotoxicity assays.

Targeting the bacterial cell wall for antibiotic drug discovery

Principal Advisor: Professor Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

Associate Advisors: Prof Rob Capon (IMB; r.capon@imb.uq.edu.au), Dr Zeinab Khalil (IMB; z.khalil@uq.edu.au), Dr Alun Jones (IMB) and Dr Rudi Sullivan (IMB)

There is an urgent need to develop new antibiotics to address the global challenge of antimicrobial drug resistance (AMR). The membrane steps in bacterial cell wall biogenesis include verified targets for antibiotics (e.g. daptomycin, teixobactin) which cause death and lysis of a bacterial cell. Our group works on the key essential membrane steps of cell wall synthesis, including the synthesis of lipid-linked precursor, the polymerisation of the cell wall and the recycling of the carrier lipid. The PGR student will receive extensive training in molecular biology, biochemistry and mass spectrometry techniques and develop novel, innovative assays to measure the activities of membrane-bound cell wall enzymes. The PGR student will then use these new assays to search for new inhibitors from Nature that inhibit the bacterial cell wall in the Australian Soil for Science microbe collection. The student will characterise the activity of hit molecules by bacterial cell biology techniques and assess their potential to be developed into new antibiotics.

References:

1. Egan et al. 2020. Regulation of peptidoglycan synthesis and remodelling. Nature Reviews Microbiology 18, 446–460.

2. Oluwole et al. 2022. Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients. Nature Communications 13:2278.

Targeting the oxytocin receptor for breast tumour reduction

Principal Advisor: A/Prof Markus Muttenthaler (m.muttenthaler@imb.uq.edu.au)

Associate Advisor: A/Prof Loic Yengo (l.yengo@imb.uq.edu.au)

Over half a million women die from breast cancer annually (>3,000 in Australia), affecting one in eight women. It is therefore important to pursue new drug targets to improve therapy and patient survival. The oxytocin/oxytocin receptor (OT/OTR) signalling system plays a key role in childbirth, breastfeeding, mother-child bonding and social behaviour. It is also involved in breast cancer, where it modulates tumour growth, including subtypes such as triple-negative breast cancer that remain difficult to treat.

This project will investigate OT/OTR’s role in tumour growth and metastasis and assess its therapeutic potential in breast cancer management. It will focus on the OTR-specific tumour growth and metastasis pathways and on developing therapeutic leads derived from nature to reduce tumour growth. Anticipated outcomes include a better understanding of OT/OTR’s role in breast cancer and new therapeutic leads for an alternative treatment strategy.

The candidate should have a degree in biochemistry, pharmacology or cell biology, good hands-on laboratory skills, some bioinformatics skills (e.g., ability to implement statistical tests in R/Python and program scripts to automate analyses) and strong ambition and work ethics. The candidate will be involved in genetic/bioinformatic analysis, cancer cell signalling assays, chemical synthesis of OT ligands, GPCR pharmacology and characterisation of therapeutic leads in breast cancer models.

The discovery and development of highly stable venom-derived peptide drug leads

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

Associate Advisor: A/Prof Johan Rosengren (UQ School of Biomedical Sciences)

Venoms comprise a highly complex cocktail of bioactive peptides evolved to paralyse prey and defend against predators. The homology of prey and predator receptors to human receptors renders many of these venom peptides also active on human receptors. Venoms have therefore become a rich source for new neurological tools and therapeutic leads with many translational opportunities.

This project covers the discovery, chemical synthesis, and structure-activity relationship studies of venom peptides, with a specific focus on gastrointestinal stability and drug targets in the gut. Venom peptides are known for their disulfide-rich frameworks supporting secondary structural motifs not only important for high potency and selectivity but also for improved metabolic stability. While primarily studied for their therapeutic potential as injectables, this project will break new ground by investigating evolutionarily optimised sequences and structures that can even withstand gastrointestinal digestions, thereby providing new insights for the development of oral peptide therapeutics targeting receptors within the gut. These therapeutic leads will have enormous potential for the prevention or treatment of gastrointestinal disorders or chronic abdominal pain.

The candidate should have a degree in synthetic chemistry, biochemistry or pharmacology, good hands-on laboratory skills, and strong ambition and work ethics. The candidate will be involved in solid phase peptide synthesis, medicinal chemistry, mass spectrometry, NMR structure determination, CD studies, structure-activity relationship studies, gut stability assays, and receptor pharmacology.

Understanding the molecular structures of proteins involved in rare disease

Principal Advisor: Dr Rosemary Cater (r.cater@uq.edu.au)

Associate Advisor: Dr Brett Collins (b.collins@imb.uq.edu.au)

Rare diseases are often caused by genetic mutations that disrupt protein function. In some cases, we already understand the three-dimensional structure and functional role of these proteins in healthy individuals. However, unfortunately, for some rare diseases, we lack this knowledge. This lack of information prevents us from understanding how mutations within the protein can lead to malfunction and disease onset, which in turn prevents us from understanding the disease and how to treat it. This project will employ biochemical techniques, structural biology (cryo-EM), and computational approaches to understand the normal 3D structure and role of proteins implicated in rare diseases. By elucidating these aspects, we will provide critical insights for the development of drugs to treat these rare diseases.

Unveiling Potential Drug Candidates for Inflammatory Bowel Disease within the Rich Tapestry of the Australian Microbiome

Principal Advisor: Dr Zeinab Khalil (z.khalil@uq.edu.au)

Associate Advisor: Dr Angela Salim (a.salim@imb.uq.edu.au), Professor Rob Capon (r.capon@imb.uq.edu.au) and Dr Rabina Giri (Mater Health)

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, encompassing disorders like Crohn's disease and ulcerative colitis. With existing treatments often falling short, there's a growing need for innovative solutions.

In 2020, we initiated the Soils for Science (S4S) project, a nationwide citizen science endeavor collecting soil samples from backyards across Australia. Within this diverse microbial landscape, we seek answers to IBD.

Our mission involves annotating the S4S microbe library, prioritizing genetically and chemically unique microbes. Through cultivation profiling and fermentation, we aim to harness the untapped potential of these microbes for drug discovery. The ensuing chemical analysis will isolate, identify, and evaluate new compounds with the potential to revolutionize IBD treatment.

Join our multidisciplinary team and dive into the world of analytical, spectroscopic, and medicinal chemistry, guided by microbiological and genomic sciences. Together, we are poised to unlock nature's secrets and pave the way for groundbreaking treatments for Inflammatory Bowel Disease.

Venom-derived peptides to study heart function and treat cardiovascular disease

Principal Advisor: A/Prof Markus Muttenthaler (m.muttenthaler@imb.uq.edu.au)

Associate Advisor: A/Prof Nathan Palpant (n.palpant@uq.edu.au)

Cardiovascular disease is the leading cause of death in the world. Although therapies have improved, mortality remains high, and 1 in 5 people develop heart failure, resulting in global annual healthcare costs of $108 billion. Innovative solutions are therefore required to develop new therapies for heart disease.

Venoms comprise a complex cocktail of bioactive peptides that target many human receptors and are therefore a rich source of new pharmacological tools and therapeutic leads. This project focuses on identifying and developing such new tools and leads with interesting functions on the human heart.

Techniques will include venom-heart-function screens, tissue culture, proteomics, chemical synthesis and structure-activity relationship studies. Identified compounds will support the study of heart function and might lead to innovations in the prevention or treatment of cardiovascular disorders.

The candidate should have a degree in biochemistry, pharmacology and/or cell biology, good hands-on laboratory skills, and strong ambition and work ethics.

All PhD projects qualify for a UQ Graduate School Scholarship. When you have chosen a project (or wish to devise a new project), please contact the Principal Advisor via email ensuring the project title (or proposed project title) is in the subject line and your latest CV is attached. Once you have confirmation that they will endorse you for your project, you may officially apply via the UQ Application Portal making sure you select 'UQ Graduate School Scholarship' when you do so.

A new strategy to treat chronic liver disease

Principal Advisor: Prof Irina Vetter (IMB)

Associate Advisor: A/Prof Frederic Gachon (IMB)

Non-alcoholic fatty liver disease (NAFLD) is a severe health burden which can progress to cirrhosis and hepatocellular carcinoma. Associated with obesity and a sedentary lifestyle, NAFLD affects around 25% of the world’s population and up to 90% of people with morbid obesity. To date, there are no treatment possibilities available for NAFLD and therapeutic strategies are highly sought after. We recently demonstrated that the size of the liver fluctuates over the day. These daily fluctuations are regulated by circadian and feeding rhythms and accompany the daily rhythms of nutrient storage, drug detoxification and ribosome biogenesis. While high amplitude circadian rhythms are associated with a healthy liver, the rhythmicity of liver size and physiology are attenuated in obesity and liver disease. Our preliminary data suggests that the regulation of ion channels play a role in liver size fluctuation and the development of liver fibrosis. This project aims at identifying new small molecules targeting these ion channels to target liver size with the aim to restore normal liver physiology and counteract the development or even cure NAFLD, opening new avenues for treatment and prevention of NAFLD.

AI and Mechanical Ventilation

Bioengineering of novel nanovesicles for drug delivery

Characterising a specific regulator of venous vessel integrity

Principal Advisor: Dr Anne Lagendijk (IMB)

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

Our blood vasculature forms a protective barrier between the blood and surrounding tissues. Blood vessels are kept intact by building strong connections between cells that line the blood vessel wall. These connections are established by adhesion proteins. We have uncovered that adrenomedullin peptides can control adhesion in veins but not arteries. This project aims to understand how adrenomedullin controls venous adhesion so specifically and if this is conserved between species. We will examine this using uniquely suitable mammalian models. The project aims to improve our understanding on how to strengthen vessels and holds the potential to enhance tissue engineering and will expand the scope of Australian research.

De-risking the drug development pipeline by finding biomarkers of drug action

Principal Advisor: Associate Professor Nathan Palpant (n.palpant@uq.edu.au)

Associate Advisors: Dr Sonia Shah (sonia.shah@imb.uq.edu.au) and Professor Glenn King (glenn.king@imb.uq.edu.au)

Greater than 90% of drugs fail to advance into clinical approval. Genetic evidence supporting a drug-target-indication can improve the success by greater than 50%. This project aims to make use of consortium-level data resources (UKBiobank, Human Cell Atlas, ENCODE etc) to identify genetic links between genetic targets and phenotypes to help facilitate the translation of drugs from healthy individuals (Phase 1 clinical trial assessing safety) into sick patients (Phase 2 clinical trial assessing efficacy). Finding orthogonal biomarkers of drug action in healthy individuals is critical to de-risk drug dosing when transitioning from Phase 1 to Phase 2 trials. Using ASIC1a as a candidate drug being developed to treat heart attacks, this project will develop a functionally validated computational pipeline to predict orthogonal biomarkers of ASIC1a inhibitor drug action in healthy individuals to help inform dosing in human clinical trials. Computationally predicted biomarkers will be validated using genetic knockout animals and pharmacological inhibitors of ASIC1a. Collectively, this project will help develop proof-of-principle computational pipeline for orthogonal biomarker prediction of drug targets in the human genome.

Developing new therapeutic and diagnostic tools for tissue ischemia

Principal Advisor: Associate Professor Nathan Palpant (n.palpant@uq.edu.au)

Associate Advisors: Professor Glenn King (glenn.king@imb.uq.edu.au)

The research project will test the hypothesis that acid sensing ion channel 1a (ASIC1a) mechanistically underpins ischemia-induced injury across diverse organs and thus provides both a diagnostic marker and a therapeutic target for tissue ischemia. While ischemic injuries to the heart and brain in the form of heart attack and stroke are the most significant contributors to the global burden of disease, all organs are susceptible to ischemic injury whether in the context of patient care or during the procurement and storage of organs for transplantation. My laboratory aims to accelerate the diagnosis and prevention of organ damage due to tissue ischemia. This project stems from our elucidation of ASIC1a as a novel target for ischemic injuries and our discovery of Hi1a, the most potent known inhibitor of this channel, from venom of an Australian funnel-web spider. In preclinical studies we showed that Hi1a is a safe and potent therapeutic that reduces brain injury after stroke, improves recovery after a heart attack, and enhances the performance of donor hearts procured for transplantation. These remarkable therapeutic properties stem from Hi1a’s ability to protect cells from ischemic injury by inhibiting ASIC1a. Exciting preliminary data demonstrating that Hi1a interacts only with ASIC1a in tissue regions experiencing acute ischemia and not in healthy or the remote zone of injured tissue. This presents a unique opportunity to develop Hi1a as a diagnostic tool (theranostic) to measure the progression of ischemic injuries using clinical imaging methods. This project will develop peptidic ASIC1a inhibitors as a diagnostic marker of tissue ischemia. We will develop radiolabelled peptides that bind to ASIC1a with high affinity to image the progression of organ ischemia in vivo using positron emission tomography-magnetic resonance imaging (PET-MRI). The project will also determine the temporal-spatial activation of ASIC1a-Hi1a interactions across organ systems in response to acute acidosis. Using a murine model of global hypercapnic acidosis, we will determine ASIC1a-Hi1a interactions at a tissue and sub-cellular level during acute ischemic stress to reveal the broader therapeutic landscape for ASIC1a inhibitors. The over-arching goal of this project is to understand the biology of ASIC1a stress response mechanisms across diverse organ systems.

Early warning mechanisms for epithelial tissue self-protection

Principal Advisor: Prof Alpha Yap (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

This project aims to discover how epithelial tissues in the body protect themselves against cell injury and cancerous transformation through the early detection and elimination of abnormal cells. Epithelia are found in major organs, such as the lung, breast and gastrointestinal tract - tissues that are common sources of major diseases, such as inflammation and cancer. The Yap group has pioneered work to understand how mechanical forces are detected as early warnings of cellular dysfunction in epithelia. Conversely, we have found that abnormal tissue mechanics may increase the susceptibility of epithelial tissues to disease. We aim to understand how mechanical signals are detected, how they may be disturbed, and whether correcting mechanics can improve disease outcomes. We work at the interface between experimental biology and theoretical physics. So, projects can be tailored to student's interests, but will give experience in experimental cell biology and physical theory.

Endometrial stem cell maturation and its role in reproductive disease

Principal Advisor: Dr Brett McKinnon (IMB)

Associate Advisor: A/Prof Emaneual Pelosi (UQ Centre for Clinical Research)

The endometrium is a key organ of the reproductive system. It is a complex biological structure of epithelial glands, vascularised stroma and infiltrating immune cells that require intimate communication for normal function. The endometrium is unique in that it undergoes cyclical shedding and regeneration each month regenerated from the resident mesenchymal stem and epithelial progenitor cells in the basalis layer. The maturation and differentiation of these cells into a fully functional endometrium must be tightly regulated. Variations in this maturation from stem cell to mature cell could lead to aberrant cell subsets that increase disease susceptibility and underpin disease variations.

We propose to apply complex organoid and translation models to study stem cell maturation in the endometrium, identify the relationship between altered maturation and molecular signatures of disease and identify the potential to personalise treatment based on these signatures. We will use a combination of single-cell and spatial multi-omics data to determine gene and protein expression and quantitative microscopy to map endometrial maturation and its relationship to reproductive disease. This project will develop skills in both wet-lab and dry-lab techniques incorporating experimental design, performance and data analysis.

Endothelial stabilisation and resuscitation in septic shock

How does abnormal light exposure affect Alzheimer’s disease progression?

Principal Advisor: Dr Benjamin Weger (IMB)

Associate Advisor: Dr Juergen Goetz (QBI); A/Prof Frederic Gachon (IMB)

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. One of the factors that may contribute to AD development and progression is chronodisruption, which occurs when the circadian clock is misaligned with the environmental light-dark cycle. This can happen due to shift work, aging, or exposure to aberrant light patterns. Chronodisruption can impair cognitive performance, mood, and sleep quality in people with AD. Moreover, it can precede the onset of clinical symptoms by several years. Bright light therapy has been shown to improve some of these aspects in AD patients, suggesting a causal link between light exposure, chronodisruption and AD.

In this project, we will use a mouse model of AD that exhibits early cognitive impairment and expose it to an aberrant light regimen that mimics the disrupted light environment often experienced by people with AD. We will assess the effects of this regimen on circadian rhythms, memory and learning abilities and molecular markers of AD pathology. This project will reveal how aberrant light exposure influences AD progression and provide insights for developing chronotherapeutic strategies that could slow down or prevent AD.

Host-Microbe Interactions and the circadian clock in Liver Disease

Principal Advisor: Dr Benjamin Weger (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2026, which means you must apply no later than 30 September, 2025.

Non-alcoholic fatty liver disease (NAFLD) is a major global health problem and refers to a spectrum of liver conditions including simple steatosis, non-alcoholic steatohepatitis and fibrosis. NAFLD affects at least 25% of adults in developed nations and is a leading cause of cirrhosis and hepatocellular carcinoma, but current treatment options remain limited.

Increasing evidence points to a crucial role of gut microbiota in the pathophysiology of NAFLD, yet the underlying mechanisms remain scarcely understood. This PhD project is based on our findings that microbiota modulates growth hormone (GH) secretion of the host (microbiota-GH axis) to regulate diurnal/circadian liver physiology in a sex-dependent manner.

The study will explore the role of an altered microbiota-GH axis in NAFLD progression and will test whether its targeted modulation may provide a new way for treating NAFLD. This project involves a multi-omics approach and combines innovative cell culture and pre-clinical models of NAFLD. Students with an interest in liver physiology and/or the circadian clock are encouraged to apply.

How epithelial tissues detect and respond to cell death and injury

Principal Advisor: Professor Alpha Yap (IMB)

Associate Advisor: TBC

Two PhD projects are available as part of Professor Yap’s ARC Laureate Program which commences in 2024. This prestigious 5-year program aims to understand how cells communicate with one another by mechanical force to detect injury in epithelial tissues such as the gastrointestinal tract and embryonic skin. We apply physical and cell biological approaches to understand how those mechanical forces are generated and detected for tissue health and repair. We use innovative approaches from different disciplines, including live-cell microscopy and genetic manipulation in zebrafish embryos; experimental tools and theory from physics that provide new ways to understand the biological phenomena; and testing how failure of mechanical communication may allow injury to disrupt tissue integrity. Individual projects will be designed that emphasize different aspects within this overall program, tailored for the specific interests of students, which can range from biology to biological physics. Independent of the specific focus of an individual project, the interdisciplinary range of this Laureate Program provides an exciting opportunity for students to train across biological and physical disciplines, to enhance their capacity and versatility for the future.

Research Environment

These projects will be supported by the world-class resources of the IMB and the network of national and international experts who are collaborating with Professor Yap’s ARC Laureate Program. Depending on the specific requirements of each project, students have the opportunity to learn cutting-edge experimental approaches, such as biophysical techniques to analyse tissue mechanics and the use of organoids and zebrafish embryos to model cell injury and tissue responses. This project is part of a program that provide a rich, interdisciplinary network for their training. Local collaborators bring experience in cell biology (Prof. Rob Parton, Dr. Samantha Stehbens), zebrafish models (Dr Anne Lagendijk),inflammation (Professors Kate Schroder and Matt Sweet) and gastrointestinal function (Professor Jake Begun, MMRI-UQ); while national and international collaborators bring expertise in mechanobiology (e.g. Richard Morris, UNSW; Virgile Viasnoff, Nat Uni Singapore; Phillipe Marcq, ESPCI Paris). More broadly, the IMB and UQ campus provide a vibrant, multidisciplinary environment for this training, where they will get exposure to disciplines such as developmental biology, gastroenterology and genomics, as well as the cell biology and biophysics of the host lab.

Hypothermic organ preservation (HOPE) to improve donor heart availability

Principal Advisor: Dr Jacky Suen (j.suen1@uq.edu.au)

Associate Advisor: Professor John Fraser (j.fraser@uq.edu.au)

Donor hearts are extremely sensitive to time once extracted from donor, with increasing time directly associated with increased graft dysfunction and patient mortality. The PhD fellow will work with leading clinical scientists in cardiac transplantation to push the boundary of donor heart preservation. Our previous work has extended the allowable storage time from 4 to 8 hours. This PhD will be the first worldwide to examine the feasibility to further extend this beyond 12 hours. This study is funded by an NHMRC Ideas grant.

Identifying novel factors that can reduce severity of stroke-prone vascular malformations

Principal Advisor: Dr Anne Lagendijk (a.lagendijk@uq.edu.au)

Associate Advisor: Samantha Stehbens (AIBN/IMB; s.stehbens@uq.edu.au)

Cerebral Cavernous Malformation (CCM) is a progressive vascular disease whereby focal clones of defective endothelial cells give rise to distinctive bulging vascular lesions. The endothelial cells in progressed lesions show reduced adhesion with each other as well as cellular thinning and spreading. CCM lesions form exclusively in venous vessels of the central nervous system (CNS: brain and spinal cord), at a surprisingly high frequency of up to 0.5% of the population. Due to their location and fragile structure CCMs cause chronic headaches, seizures, and stroke. CCM disease is induced by mutations in one of three CCM genes: CCM1, CCM2, or CCM3 which leads to uncontrolled KLF2/4 transcription factor activity.

We recently identified novel factors that are downregulated in CCM disease, and when these factors are fully absent CCM phenotypes worsen. This project will investigate these new players using zebrafish and bioengineered 3D vessel-on-a-chip models and determine these might prevent CCM progression.

Identifying vascular cell types and genes involved in human skeletal disease

Principal Advisor: Dr John Kemp (IMB)

Associate Advisor: Dr Anne Lagendijk (IMB); Dr Dylan Bergen (University of Bristol, UK)

Genetic association studies offer a means of identifying drug targets for disease intervention. However, few of the causal genes underlying skeletal disease associations have been identified and functionally validated in vivo. Our team has developed a workflow that integrates genetic association study results, single-cell transcriptomics, and phenotype data from knockout animal models to identify disease-causing genes and predict the cellular context through which they function. Unpublished results from our team suggest that vascular cell-specific genes have underappreciated roles in bone homeostasis. This PhD project aims to better understand how vascular genes contribute to the development of skeletal disease.

Research objectives:
(i) To define a single-cell RNA sequencing census of different cell types, present in the bone microenvironment of zebrafish, and contrast the transcriptomic profiles of different bone cells across mice, and humans.
(ii) Investigate whether profiles of different bone cell types are conserved across species, and whether vascular cell types are also enriched for skeletal disease associated genes.
(iii) Identify candidate vascular cell-specific genes (and drug targets) and validate their predicted roles in skeletal disease using zebrafish knockout models and live imaging to monitor vessel network formation and function.

Impact of the sex-specific growth hormone secretion on the pathogenesis of type 2 diabetes

Principal Advisor: A/Prof Frederic Gachon (IMB)

Associate Advisor: Dr Frederik Steyn (UQ School of Biomedical Sciences)

Associated with obesity and a sedentary lifestyle, T2D affects around 10% of the world’s population, mainly associated with morbid obesity. T2D starts with a pre-diabetic state characterized by an increased blood glucose level caused mainly by insulin resistance. As insulin overproduction occurs over a long period of time, insulin-producing pancreatic beta-cells lose their capacity to produce insulin, defining the beginning of T2D. Associated with obesity, insulin resistance is triggered by inflammation and fibrosis initiated by lipid accumulation. Metabolic diseases, including T2D, are characterized by a strong sex-specific difference of incidence defined by sex-dependent physiology and metabolism. This sex-specific difference is caused, in part, by the dimorphic secretion pattern of growth hormone (GH) between males and females. Interestingly, GH secretion is perturbed during T2D and has been associated with the development of the disease. However, in both human and animal models, changes in GH secretion protects against T2D, even in obese individuals. Therefore, we hypothesize that modulation of GH secretion pattern could be a protective response of the organism to counteract the development of T2D. The goal of this project is to test this hypothesis, opening new avenues for the treatment of T2D using time resolved sex-specific administration of GH.

Inflammasome inhibitors in disease: Is there a therapeutic trade-off of compromised host defence?

Principal Advisor: Prof Kate Schroder (IMB)

Associate Advisor: Dr Sabrina Sofia Burgener (IMB); Prof Avril Robertson

Inflammasome inhibitors offer tremendous promise as new disease-modifying therapeutics. Inflammasomes are signalling platforms with caspase-1 (CASP1) protease activity that induce potent inflammatory responses, including pathological inflammation and disease in many human conditions, such as chronic liver disease. Inflammasomes are thus exciting new drug targets, with inhibitors of one inflammasome (the NLRP3 inflammasome) entering Phase 2 clinical trials for the treatment of genetic auto-inflammatory disease and neurodegenerative diseases. Inhibitors that target multiple inflammasomes (e.g. CASP1 inhibitors) are currently under development for treating diseases driven by multiple inflammasomes (e.g. chronic liver disease). But the beneficial functions of these new therapeutics might come at a cost – a “trade-off” – of promoting patient susceptibility to infection. This is because inflammasomes also exert protective functions in host defence against microbes. For example, the NLRP3 inflammasome is essential for host defence against the clinically-important fungus Candida albicans limiting fungal dissemination and reducing disease, while in immunocompromised patients, C. albicans causes severe and life-threatening infections.

This project seeks to understand whether the future clinical use of inflammasome inhibitors for inflammatory disease treatment may come with the therapeutic trade-off of compromised host defence against C. albicans.

Introduction of VR and other technologies in ICU and patient outcomes

Investigating the importance of blood flow pattern for advanced life support

Principal Advisor: Dr Jacky Suen (j.suen1@uq.edu.au)

Associate Advisor: Professor John Fraser (j.fraser@uq.edu.au)

Increasing number of patients with critical cardiac-respiratory failure is supported by advanced life support. Yet, certain conditions have failed to see any improvement in patient outcomes. The PhD fellow will work with industry leader to examine and develop the next generation advanced life support. Our previous study demonstrated superiority of pulsatile blood flow in supporting patients with cardiogenic shock. This PhD will focus on further understanding the underlying physiological and biological impact of blood flow pattern.

Investigating the molecular basis of motor neurone disease

Principal Advisor: Dr Fleur Garton (IMB)

Associate Advisor: Dr Adam Walker (QBI); Dr Allan McRae (IMB)

Motor neuron disease (MND) is a devastating disease for those affected and their family. It is an adult-onset, neurodegenerative disorder that progressively leads to paralysis and death. For most individuals with MND, diagnosis comes as a surprise, with no family history. The estimated genetic contribution to disease is significant and genome-wide association studies (GWAS) are now identifying these. The causal gene/mechanism is not known and further analyses must be carried out.

This project aims to identify molecular mechanisms contributing to MND to help support the path to translation. It will harness the in-house, Sporadic ALS Australia Systems Genomics Consortium (SALSA-SGC) platform. The current cohort, N~400 cases and N~200 controls is larger than existing datasets and has a rich set of matched data both genomic and clinical. Samples will be run for ‘omics analyses including DNA methylation and RNA-seq. Profiling expression with genomic and clinical data is expected to help identify lead disease mechanisms. Any new finding can be modelled in-vitro or in-vivo using cell or animal models. There is no effective treatment for MND and this project will help drive progress in unlocking molecular variations that contribute to the disease.

Lipid droplets and immune defence

Principal Advisor: Professor Rob Parton (r.parton@imb.uq.edu.au)

Associate Advisor: Dr Harriet Lo (h.lo@imb.uq.edu.au) and Dr Tom Hall (t.hall5@uq.edu.au)

We recently discovered a novel process whereby eukaryotic cells are able to kill invading pathogens using lipid droplets. This project will use cell-based infection models and live imaging in zebrafish to identify and characterise the proteins involved.

Microenvironmental regulation of Melanoma Brain Metastasis

Principal Advisor: Dr Melanie White (IMB)

Associate Advisor: Dr Samantha Stehbens (AIBN); Prof Alan Rowan (AIBN)

Despite significant progress by scientists and clinicians, melanoma is often fatal due to rapid spread throughout the body, especially to the brain. The brain is vastly different to other tissues, and melanoma is particularly efficient at travelling to the brain and surviving in the new environment to establish disease there. Clinically, it is difficult to stop melanoma spreading to the brain and once it is there, it is complicated to treat. This is because melanoma in the brain is distinct due to the differences in the tissue structure and types of cells surrounding the tumour. This project will seek to develop novel integrative cancer models including cell biology and quail embryo xenograft models, to understand how melanoma survives in the brain microenvironment. By understanding crosstalk, we aim to identify a novel mechanism to block transmission of signals from the tumour microenvironment- inhibiting melanoma proliferation, survival, and invasion. This project is cross-disciplinary integrating cell biology with neuroscience and vascular biology.

Migration dependent signalling in immune cells

Principal Advisor: Prof Jennifer Stow (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

Immune cells migrate through tissues to sites of infection or damage to provide immune defence and to promote tissue repair. Using advanced live cell imaging we can detect trails left by migrating immune cells that help guide other cells to sites of infection. This project will characterise this new form of signalling between cells, uncovering new aspects of immune cell migration vital for fighting infection and wound healing. The project will build skills in cutting edge cell and tissue microscopy and imaging, including in model organisms and organoids, and involve biochemical and genetic analyses. The project is a collaboration between 3 universities with the potential for cross disciplinary research and training in a diverse team.

Mitochondrial transplantation to improve donor heart function

Principal Advisor: Dr Jacky Suen (j.suen1@uq.edu.au)

Associate Advisor: Professor John Fraser (j.fraser@uq.edu.au)

This project focuses on the use of mitochondria transplantation to improve the quality and function of donor heart, in order to reduce the risk of primary graft dysfunction, as well as improving utility of marginal donor heart. Currently up to 80% of hearts were discarded, partly due to existing conditions. This is becoming an increasing problem as Australian faces an aging population. The fellow will work closely with our collaborator at Harvard Medical School and initial funding awarded from the Heart Foundation.

Modelling human genetic variants for muscle and adipose phenotypes using the zebrafish

Modulating G protein-coupled receptors in chronic inflammatory diseases

Principal Advisor: Prof David Fairlie (IMB)

Associate Advisor: A/Prof David Vesey (ATH, UQ Faculty of Medicine and Department of Nephrology, Princess Alexandra Hospital); Dr James Lim (IMB)

G protein-coupled receptors (GPCRs) are membrane-spanning proteins expressed on the cell surface and they act as signalling mediators between chemicals and proteins outside cells and signalling networks inside cells, enabling transduction of chemical signals into diverse physiological responses. Some of these receptors are the targets for about a third of all known pharmaceuticals, yet most GPCRs have not yet been sufficiently studied to become validated drug targets. We have previously discovered a number of GPCRs that are important links between extracellular signalling networks and intracellular metabolic signalling networks that drive inflammation and inflammatory diseases. This project will investigate the signalling connections between cellular activation of GPCRs and immunometabolic outputs that drive mouse models of chronic inflammatory/fibrotic disease associated with the liver/kidney. Techniques to be applied include PCR, western blots, cell culture, CRISPR-Cas9, flow cytometry, fluorescence microscopy, ELISA, G protein and b-arrestin signalling, GPCR secondary messenger assays (Ca2+, cAMP, ERK, Rho, arrestins, etc) and administration of experimental drugs to mouse models of chronic disease, measurement of metabolic, inflammatory and disease markers in tissues and cells. The project will be aided by availability of unique small molecule GPCR modulators, developed by chemists in our team, as probes and experimental drugs for various diseases.

Multi-modal biosensors for cell polarity and migration

Principal Advisor: Prof Jennifer Stow (IMB)

Associate Advisor: Dr Nicholas Condon (IMB); Prof Halina Rubinsztein-Dunlop (UQ School of Mathematics and Physics)

Epithelial cells and neurons are permanently polarised in order to perform directional transcytosis, endocytosis and secretion of many substances. This polarity is essential for allowing epithelial cells to act as selective barriers and for neurotransmission in neuronal networks. Many other cell types become transiently polarised, for instance while they are migrating, when they reorient to have a front and back. Measuring cell polarity is important for understanding both how cells and tissues normally function and the loss of function associated with genetic diseases, cancer, infection and inflammatory disease. This PhD project will create cellular models for measuring polarity and assessing loss of polarity after gene deletions. We will develop a suite of bifunctional, genetically-encoded biosensors as biological and biophysical detectors to measure polarised membrane domains in living cells. Model epithelial cells and neurons expressing these biosensors will be established as 3D organoids or in migration chambers and used to define polarity and to explore loss of polarity.

Novel pathways of stress signalling in cancer

Principal Advisor: Prof Rob Parton (IMB)

Associate Advisor: Dr Alan Rowan (AIBN); A/Prof Alpha Yap (IMB)

Caveolae, abundant cell surface organelles, have been extensively linked to chronic disease. Changes in the major proteins of caveolae have been linked to numerous cancers including breast cancer, pancreatic cancer, melanoma, thyroid cancer, gastric cancer, and colorectal cancer. In addition, caveolar proteins are dramatically upregulated in cells treated with chemo-therapeutics and their loss sensitises cells to toxic agents. Understanding the role of caveolae in cancer susceptibility and progression (to invasion and metastasis) requires a complete understanding of how caveolae, both in the cancer cell and the cancer cell environment, respond to intrinsic risk factors and to external stress.

This project will build on our findings that caveolae can sense mechanical and environmental stress. It will test the hypothesis that caveolae can protect cells against mechanical forces by activating signalling pathways from the cell surface to the nucleus and that loss of this pathway can promote DNA damage leading to cancer progression. It will employ novel systems in which defined mechanical stimuli can be combined with genetically-modified cells and state-of-the-art microscopic methods. This will define the role of caveolae in both the host cells, and in the neighbouring cellular environment, and determine the contribution of caveolar dysfunction to cancer progression.

Optimising light-driven microalgae cell factories: Biochemical studies of Photosystem II mutants and their light harvesting systems

Principal Advisor: Professor Ben Hankamer (b.hankamer@imb.uq.edu.au)

The global transition to reach Net Zero carbon dioxide emissions by 2050 is forecast to require US$144 trillion (or $5.5 trillion annually to 2050) of investment, highlighting an extraordinary opportunity to develop renewable technologies.

The sun is by far the largest renewable energy resource available to us, and every 2 hrs provides Earth with more energy than is required to power our entire global economy for a year.

Oxygenic photosynthetic organisms including plants, algae and cyanobacteria (and the intricate photosynthetic machinery within them) form the biological interface between the sun and our biosphere. Over 3 billion years, these intricate photosynthetic interfaces have evolved to capture this solar energy and CO2 to generate oxygen and biomass that provide the food, fuel, biomaterials, and clean water that support aerobic life on Earth.

The first step of photosynthesis and all light-driven biotechnologies is light capture by the Light Harvesting Complex (LHC) proteins associated with Photosystems I and II. This PhD project will focus on biochemically and functionally defining key LHC trimers and ~ 1MDa photosynthetic supercomplexes. This work supports the structure-guided design of next-generation high-efficiency CRISPR-engineered cell lines for light-driven biotechnology applications.

The successful PhD candidate will be part of a strong multi-disciplinary team in the Centre for Solar Biotechnology (CSB; 30 international teams, ~35 industry partners to date) within the Institute for Molecular Bioscience (IMB) at the University of Queensland (UQ). The IMB is one of Australia’s premier life sciences institutes and ranks highly internationally. UQ regularly ranks in the top 1% (top 50) universities internationally.

The CSB and our industry partners are focused on developing advanced light-driven biotechnologies based on single cell green algae that tap into this huge solar energy resource and use it to drive the production of a broad range of products from high-value recombinant proteins through to cost-competitive renewable fuels. The IMB has excellent protein biochemistry facilities (protein purification, cryo-electron microscopy and mass spectrometry) as well as powerful robotic systems (to screen for high-efficiency cell lines) to support this work.

The project will involve microalgal cell culture, light microscopy, purification of photosystem complexes by sucrose density gradient centrifugation and FPLC, biochemical and biophysical analyses of these complexes, negative stain and cryo-electron microscopy. They will also have the opportunity to use the state-of-the-art cryo-EM facilities to collect atomic resolution images for single particle analysis.

Peptide absorption in the gastrointestinal tract and development of peptide drugs

Principal Advisor: Prof Jennifer Stow (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

This student project is part of a grant-funded industry partnership, with partners at UQ/IMB and Monash U/MIPS and an international pharmaceutical company. As a student member of this team you will receive exceptional training and work experience at the interface between research in academic and industry settings. The project will be part of a broader program investigating how peptides and peptide drugs are absorbed across the wall of the gastrointestinal tract (GIT); multidisciplinary approaches are being taken by the team and the student project will be focussed on using multiple modes of microscopy to examine peptide uptake and distribution. Confocal microscopy, live imaging of cells, organoids, explants and tissues, will be employed, using cutting edge equipment and state of the art technologies; there will be some biochemical and protein studies and you will be involved in quantitative image analysis and handling of big image data. Throughout the project you will work with world class experts for training, supervision and technical innovations. The project will be based at UQ (Brisbane) and involve active interstate and international collaborations. You will emerge from this project with translatable skills, work experience and scientific outputs, having contributed to a project that will have practical outcomes and global impact.

Sleep & Circadian Rhythms in ICU

Targeting macrophage-mediated chronic inflammation

Principal Advisor: Prof Matt Sweet (IMB)

Associate Advisor: Prof Michael Yu (AIBN)

Macrophages are key cellular mediators of innate immunity. These danger-sensing cells are present in all tissues of the body, providing frontline defence against infection and initiating, coordinating, and resolving inflammation to maintain homeostasis. Dysregulated macrophage activation drives pathology in numerous inflammation-associated chronic diseases, for example chronic liver disease, inflammatory bowel disease, rheumatoid arthritis, atherosclerosis and cancers. Emerging technologies, including nanoparticle-mediated delivery of mRNAs and small molecules, provide exciting new opportunities to target otherwise "undruggable” intracellular molecules and pathways within macrophages. Such approaches hold great potential for manipulating macrophage functions to suppress inflammation-mediated chronic disease. This project will characterize and target specific pro-inflammatory signalling pathways in macrophages as proof-of-concept for intervention in chronic inflammatory diseases.

Understanding and preventing relapse of Inflammatory Bowel Disease

Principal Advisor: Prof Alpha Yap (IMB)

Associate Advisor: Dr Julie Davies (Mater, UQ)

The inflammatory bowel diseases, Crohn’s Disease and Ulcerative Colitis, are chronic diseases that display patterns of relapse and remission which contribute significantly to the burden that they carry. A key to reducing this burden, both for patients and the community, lies in being able to prolong how long patients stay in remission from active disease. Common approaches to maintain remission include immunosuppression and cytokine inhibitors, but these carry significant side effects and often eventually fail. In this project, we aim to investigate alternative ways to understand the mechanisms that lead to relapse, as a foundation to design new therapies. Specifically, our recent discoveries indicate that the mechanical properties of the bowel epithelium may play a critical role in relapse. Increased mechanical tension prevents the bowel epithelium from eliminating injured cells, thus increasing their capacity to provoke inflammation and disease relapse. We will pursue this by developing new clinically-applicable diagnostic tools to evaluate tissue mechanics and test how correcting mechanical properties can prevent disease relapse. Our goal is to support remission through approaches that can complement currently-available therapies.

Understanding blood vessel expansion and rupture using 3D models

Principal Advisor: Dr Emma Gordon (IMB)

Associate Advisor: Dr Mark Allenby (UQ School of Chemical Engineering)

Blood vessels are comprised of an ordered network of arteries, veins and capillaries, which supply oxygen and nutrients to all tissues of the body. Growth and expansion of the vascular system occurs during embryonic development, or in response to tissue injury or disease in the adult. As a result of their unique functions, vessels are subjected to distinct mechanical stresses that confer physical forces on cells that line the vessel wall, such as fluid shear stress, stretch and stiffness. In diseases of the vasculature, such as aortic and intracranial aneurysms, these physical forces become dysregulated, leading to changes in the shape of the vessel and eventually rupture. Using biofabrication technology and advanced imaging techniques, this project will use 3D printed models of the vasculature to study how changes in vessels occur at the molecular level in response to altered physical forces. These findings will allow us to understand how vessels may be manipulated to develop improved therapeutic strategies to prevent expansion and rupture.

Understanding how inflammation predisposes to cancer

Principal Advisor: Prof Alpha Yap (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

Chronic inflammation of epithelial organs, such as the gut, are known to predipose to cancer. But the mechanisms responsible for this predisposition are poorly understood. Elucidating such mechanisms are essential to identify patients at increased risk for cancer and present novel opportunities to decrease cancer risk.

This project builds on our pioneering discoveries to test how inflammation may increase cancer risk by altering the epithelium within which cancer originates. We recently made the exciting discovery that abnormalities in the mechanical properties of epithelial tissues may increase cancer risk by disabling the tissue's ability to eliminate newly-transformed cancer cells. Understanding how inflammation affects tissue mechanics will provide new opportunities for diagnosis and therapeutics.

This project will provide training in a wide range of modern research approaches, including advanced microscopy, bioengineered systems to study cell behaviour, and animal models of cancer development and elimination.

Understanding the genetic and phenotypic basis of rare disease variants

Principal Advisor: Associate Professor Nathan Palpant (n.palpant@uq.edu.au)

Associate Advisors: Dr Sonia Shah (sonia.shah@imb.uq.edu.au) and Professor Mikael Boden (m.boden@uq.edu.au)

Despite these powerful approaches, studies indicate that classifying variants as pathogenic occurs in only a minority of cases and among variants reported in ClinVar, a public archive of relationships between human variation and phenotype, wherein a large proportion (37%) are classified as variants of unknown significance (VUS).

This project aims to address this key gap in knowledge, involving work in computational and/or cell biology studies, depending on the student skills and interests. For computational studies, this project aims to develop methods that integrate predictive, genome-wide identifiers of pathogenicity. We will use machine learning to build non-linear prediction methods that outperform individual prediction tools in identifying genetic causes of disease and accelerating clinical diagnosis of genetic diseases. For cell biology studies, we aim to use clinical genetics data (from the Australian Functional Genomics Network) to determine pathogenicity of variants from patients with inherited cardiovascular diseases.

The approaches will include: 1) cell modelling with human pluripotent stem cells (hPSCs), a disease-agnostic and scalable platform for high-throughput hPSC variant screening. To study variants in genes such as transcription factors that are known to cause genetic diseases, we will use molecular phenotyping by genome-wide proximity labelling with DNA adenine methyltransferase (DamID) to study how disease-causing variants alter regulatory control of the genome. Collectively, this aim implements computational predictions with disease modelling as an efficient, scalable, and disease agnostic pipeline to increase the diagnostic rate of unresolved cases.

Unravelling how epithelial tissues detect and respond to cell death and injury

Principal Advisor: Prof Alpha Yap (a.yap@uq.edu.au)

We propose that a key factor lies in how cells use mechanical forces to communicate with each other. We apply physical and cell biological approaches to understand how those mechanical forces are generated and detected for tissue health and repair. We use innovative approaches from different disciplines, including live-cell microscopy and genetic manipulation in zebrafish embryos; experimental tools and theory from physics that provide new ways to understand the biological phenomena; and testing how failure of mechanical communication may allow injury to disrupt tissue health through inflammation and infection.

Individual projects will be designed that emphasize different aspects within this overall program, tailored for the specific interests of students, which can range from biology to biological physics. Independent of the specific focus of an individual project, the interdisciplinary range of this Laureate Program provides an exciting opportunity for students to train across biological and physical disciplines, to enhance their capacity and versatility for the future.

Variants of neuronal ion channels that give rise to neurodevelopmental disorders

Principal Advisor: Dr Angelo Keramidas (IMB)

Associate Advisor: Prof Irina Vetter (IMB); A/Prof Victor Anggono (QBI)

Genetic variants of ion channels that mediate neuronal electrical communication (such as voltage-gated sodium channels and glutamate-gated synaptic receptors) can cause neurological disorders that include epilepsy, ataxia, neurodevelopmental delay and autism spectrum disorder. Understanding the molecular level deficits of an ion channel caused by a variant is essential to accurate molecular diagnosis and tailoring treatment options that correct variant-specific functional deficits. This personalised approach increases the efficacy of treatment, minimises side effects.

This project focussed on variants of voltage-gated sodium channels that are key generators of neuronal action potentials, and synaptic receptors such as GABA- and glutamate-gated ion channel receptors that mediate neuronal inhibition and excitation, respectively.

The project will combine high-resolution and high-throughput electrophysiology and pharmacology as well as ion channel protein synthesis and forward trafficking to understand the pathology of ion channel variants. Standard and new treatment options will be tested against each variant to optimise treatment that is tailored to each variant.

Together these approaches will enhance our understanding of the structure and function of neuronal ion channels and improve our understanding neurological disease mechanisms and treatments.

This project will involve a close collaboration between two groups across two institutes at UQ (IMB and QBI), offering students the opportunity for cross-disciplinary training in neuroscience research with the potential for therapeutic applications for patients.

Biosynthesis of circular antimicrobial peptides

Principal Advisor: Dr Conan Wang (IMB)

Associate Advisor: Prof David Craik (IMB); Prof Ian Henderson (IMB); Dr Thomas Durek (IMB)

Circular proteins are modified in a post-translational reaction that covalently joins their N- and C-termini. Deciphering the underlying biochemical reactions may lead to the development of new drugs that are more stable and potent and may provide new tools for protein and peptide engineering. Circular bacteriocins are a unique class of these biomolecules produced naturally by bacteria and have exhibited promising activities against a wide range of refractory pathogens in both the clinic and food industry. This project aims to reveal the secrets of how certain bacterial cells produce these proteins, how they protect themselves from the effects of these antimicrobials and how these molecules kill susceptible strains.

We encourage candidates with a strong background and interests in microbiology, biochemistry and/or molecular biology and who are interested in working in a diverse research environment, to apply. The host laboratory is embedded within the ARC Centre of Excellence for Innovations in Peptide and Protein Science, and therefore there are many opportunities to collaborate with scientists nationally and internationally. The project will involve whole-genome genetic manipulations, biochemistry, structural biology, biophysics and analytical chemistry. The project will lead to a better understanding of how some of nature’s most unique proteins are produced and could lead to new industry partnerships.

Deconstructing the genetic causes of disease to discover new drug targets

Principal Advisor: A/Prof Nathan Palpant (IMB)

Associate Advisor: Dr Andrew Mallett (IMB); Dr Sonia Shah (IMB), Dr Mikael Boden (UQ School of Chemistry and Molecular Biosciences)

Industry partnership opportunities: HAYA Therapeutics; Maze Therapeutics

Despite strong vetting for disease activity, only 10% of candidate new drugs in early-stage clinical trials are eventually approved. Previous studies have concluded that pipeline drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs. This project will take advantage of increasing clinical disease data, rapid growth in GWAS datasets, drug approval databases, and innovative new computational methods developed by our team. The overall goal is to develop unsupervised computational approaches to understand what genetic models and data are most predictive of future drug successes. Underpinning this work, the project will build and implement computational and machine learning methods to dissect the relationships between genome regulation, disease susceptibility, genetic variation, and drug development. The project will not only reveal fundamental insights into genetic control of cell differentiation and function but also facilitate development of powerful unsupervised prediction methods that bridge genetic data with disease susceptibility and drug discovery. Students with background/expertise in computational bioinformatics and machine learning are ideal for this work. Informed by clinical, computational, and cell biological supervisory team, the project will have an opportunity to engage with diverse international companies through internships and collaborations to facilitate co-design of these methods for uptake in industry discovery and prediction pipelines.

Developing Models of Cancer Therapy-Induced Late Effects

Principal Advisor: Dr Hana Starbova (IMB)

Associate Advisor: Prof Irina Vetter (IMB; UQ School of Pharmacy); Dr Raelene Endersby (Telethon Kids Institute)

Treatments such as radiotherapy and chemotherapy for childhood and adult brain cancers save many lives. However, they also cause long-term debilitating adverse effects, also termed "late effects", such as pain, cognitive disabilities and sensory-motor neuropathies. Currently, no effective treatments are available, and brain cancer survivors are forced to live with long-term disabilities.

Animal models are important for the understanding of disease pathology and for preclinical testing of novel treatment strategies. However, currently there are no appropriate animal models available for the testing of late effects of cancer therapy.

To address this gap, this PhD project aims to develop in-vivo animal models of cancer therapy-induced late effects and to test the efficacy of novel treatment strategies. This project forms a foundation for future clinical studies.

Animal handling and behavioural assessments in rodents are vital for this project.

Developing new drugs targeting acid sensitive channels to treat ischemic heart disease

Principal Advisor: Prof Nathan Palpant (IMB)

Associate Advisor: Prof Jennifer Stow (IMB); Prof Brett Collins (IMB); A/Prof Markus Muttenthaler (IMB)

Industry partnership opportunities: Infensa Bioscience

This project focuses on strategies to prevent organ damage associated with ischemic injuries of the heart. There are no drugs that prevent organ damage caused by these injuries, which ultimately leads to chronic heart failure, making ischemic heart disease the leading cause of death worldwide. Globally, 1 in 5 people develop heart failure, with annual healthcare costs of $108 B. Our team has discovered a new class of molecules, acid sensitive ion channels, that mediate cell death responses in the heart during ischemic injuries like heart attacks. This project will study the function of acid sensing channels using cell and genetic approaches. We will use innovative new drug discovery platforms to find new peptides and small molecules that inhibit acid channel activity. Finally, the project will use disease modelling in stem cells and animals to evaluate the implications of manipulating these channels using genetic or pharmacological approaches to study the implications in models of myocardial infarction. The candidate will benefit from background/expertise in cell biology and biochemistry. Collectively, this project will deliver new insights, tools, and molecules that underpin a key area of unmet clinical need in cardiovascular disease. The project will be supervised by experts in drug discovery, cell biology, and cardiovascular biology and includes opportunities for internships with industry partners such as Infensa Bioscience, a new spinout company from IMB developing cardiovascular therapeutics for heart disease.

Development of peptide-based blood-brain barrier shuttles

Principal Advisor: A/Prof Markus Muttenthaler (m.muttenthaler@imb.uq.edu.au)

Associate Advisor: A/Prof. Johan Rosengren (SBMS, j.rosengren@uq.edu.au)

Development of venom-derived blood-brain barrier shuttles

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

The blood-brain barrier controls the transfer of substances between the blood and the brain, protecting us from toxic compounds while allowing the transfer of nutrients and other beneficial molecules. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. The project will involve cell culture, blood-brain barrier models and assays, proteomics, peptide chemistry, molecular biology and pharmacology. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovative discovery and chemistry strategies to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations relevant to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.

Engineering high-efficiency light-driven synthetic biology

Principal Advisor: Prof Ben Hankerman (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

Every two hours Earth receives enough energy from the sun to power our global economy for a year. The capture and use of this energy are essential to power a sustainable zero CO2 emissions future, increase international fuel security and build advanced light-driven industries as part of an expanding circular bioeconomy.

Over 3 billion years, photosynthetic microorganisms have evolved to tap into the huge energy resource of the sun and use it to synthesise a diverse array of biomolecules that collectively form biomass. This photosynthetic capacity can be adapted to create clean fuels for the future such as hydrogen and an array of high-value biomolecules.

This PhD project is focused on the development of high-efficiency light-driven single cell green algae (microalgae) cell lines that can produce hydrogen fuel from water as well as high-value molecules using advanced genetic “plug-and play” molecular biology techniques.

Building on extensive foundational work, the project will involve the design of expression vectors, cell transformation and screening, creation of specific point mutants and gene knockouts using CRISPR and their characterisation (e.g. photosynthetic physiology, H2 production). The project may extend to technoeconomic analyses of scaled up designs and lab scale validation of the proposed industrial processes.

Investigating the role and therapeutic potential of the oxytocin receptor in prostate cancer

Principal Advisor: A/Prof Markus Muttenthaler

Associate Advisor: A/Prof. Jyotsna Batra (QUT; jyotsna.batra@qut.edu.au)

Prostate cancer is the second most frequent malignancy in men worldwide, causing over 375,000 deaths a year. When primary treatments fail, disease progression inevitably occurs, resulting in more aggressive subtypes with high mortality. This project focuses on the oxytocin/oxytocin receptor (OT/OTR) signalling system as a potential new drug target and biomarker to improve prostate cancer management and patient survival. Anticipated outcomes include a better understanding of OT/OTR’s role in prostate cancer and new therapeutic leads for an alternative treatment strategy.

Modulating protein-protein interactions in disease

Principal Advisor: Prof David Fairlie (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2025, which means you must apply no later than 30 September, 2024.

Most diseases are mediated by protein-protein interactions, often fleeting contacts between large protein surfaces too shallow to sequester conventional small molecule drugs. This project will design and develop classes of new compounds at and above size limits of conventional drugs to modulate more difficult protein-activated receptors that are largely targets without drugs. To do this, the candidate will first truncate one of the binding partners to a smaller peptide and optimise its structure, composition, protein affinity, and functional potency in order to modulate the protein-protein interaction that leads to disease. This will require knowledge and skills in peptide chemistry, solid phase synthesis, HPLC purification, spectroscopy (NMR, MS, CD), and an ability and motivation to modify peptides into small bioavailable molecules using organic synthesis techniques. Some knowledge of cell biology and enzyme assays would be an advantage, as would knowledge of NMR spectroscopy. The long term goal is to design new compounds and profile them for effects on genes/proteins/cells/rodent models of immunometabolism, inflammatory diseases and cancer. Outcomes will include new knowledge of protein-protein interactions in disease; greater understanding of drug targets, disease mechanisms and effectiveness of new drug action; patentable methods and bioactive compounds; and new experimental drug leads to new medicines for preclinical development towards the clinic.

Molecular design of drugs to fight chronic human diseases and environmental pests

Principal Advisor: Dr Conan Wang (IMB)

Must commence by Research Quarter 3, 2025.

An excellent opportunity for a PhD candidate to explore cutting-edge technologies for design of bioactive proteins to fight chronic human diseases or environmental pests. A motivated individual will be immersed in a leading research institute and international team at UQ, supported by an Australian Centre of Excellence and nationally funded research programs.

Development of drugs for human benefit, whether to cure human diseases or safeguard our food resources and environmental assets, must begin with the design of bioactive lead molecules. This research program will investigate platform technologies for engineering of novel proteins, which are actively pursued by many emerging biotechnology industries. The candidate will choose one of the following major application areas of national importance.

Next-generation anti-cancer drugs
Antimicrobial agents to fight infection
Bio-friendly drugs to control agricultural pests
Natural proteins to prevent crown of thorns starfish outbreaks

A typical project will involve use of protein structure to design new drugs. The candidate could choose to use either computational design tools or molecular libraries to screen massive numbers of drug leads. This often followed by characterisation of structure and activity using biophysical, biochemical and/or biological assays.

Molecular mechanisms of jellyfish envenomation

Principal Advisor: Dr Andrew Walker (IMB)

Associate Advisor: A/Prof Nathan Palpant (IMB)

Jellyfish cause some of the most serious envenomation syndromes of all animals, responsible for >77 deaths in Australia to date and many more around the world. Two jellyfish of interest are the box jellyfish Chironex fleckeri, whose venom targets the heart to kill in as little as two minutes; and its much smaller relative the Irukandji jellyfish Carukia barnesi, envenomation by which causes a long-lasting and painful ordeal. Jellyfish also represent an ancient group of venomous animals with unique biology different from all other venomous animals. Despite this, little is known about jellyfish toxins, how they work, or how we might design therapeutics or novel treatments to ameliorate their effects. This project would involve combining state-of-the-art techniques to isolate and characterise jellyfish toxins, test them using a range of bioassays, and assess possible agents to protect from their harmful effects.

New chemical space as a source of new drug leads

Principal Advisor: Dr Zeinab Khalil (IMB)

Associate Advisor: Prof Ian Henderson (IMB); Prof Rob Capon (IMB)

To this end in 2020 we launched Soils for Science (S4S) as an Australia wide citizen science initiative, designed to engage the public, to collect 10's of thousands of soil samples from backyards across the nation, from which we will isolate 100's thousands of unique Australian microbes.

This project will annotate the S4S microbe library to prioritize those that are genetically and chemically unique. These will be subjected to cultivation profiling, and fermentation, followed by chemical analysis to isolate, identify and evaluate new classes of chemical diversity.

Applicants must have a strong background with outstanding grades in organic chemistry, and with an interest in learning multidisciplinary biosciences.

Photocontrollable probes to study neuropeptide-mediated memory formation

Principal Advisor: A/Prof Markus Muttenthaler (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

This project aims at developing next-generation molecular probes with enhanced specificity and spatiotemporal control for the study of proteins and neuropeptide signalling. It addresses recognised knowledge gaps and technical bottlenecks in neuropeptide and memory research. Expected outcomes include a deeper molecular understanding of long-term memory formation and the role of neuropeptides in this process, as well as innovative chemistry strategies and novel molecular probes to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations of relevance to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.

Targeting strategies for drug design

Principal Advisor: Prof David Fairlie (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

Selective binding of small molecules with proteins underpins most drug discovery. However, while a compound can be devised to interact with a single protein, this cannot drive the molecule into a specific location where functional modulation of the target protein only at that location is desired for therapy. Instead, designed compounds usually bind to the protein wherever it is expressed in the body and this can be deterimental to normal healthy physiology. This project will investigate a number of promising new approaches to directing protein-binding compounds to specific compartments of cells and organisms. It will require a combination of organic synthesis, medicinal chemistry, molecular modelling and chemical biology. The new approaches will be tested and optimised with the goal of inhibiting or activating desired proteins in specific compartments in order to modulate disease-causing protein functions without altering normal healthy physiology. Achieving these aims will require enthusiasm, a high degree of self-motivation, lateral thinking, strong chemical knowledge and hands-on skills in organic synthesis (solution and solid phase), NMR characterisation (including 2D NMR structure analysis), HPLC purification, mass spectrometry, and computer modelling. Some knowledge of enzyme assays and cell biology would be an advantage. The long term goal is to design new compounds and profile them for selective effects on target genes/proteins/cells/rodent models of inflammatory diseases and cancer. Outcomes will include new knowledge of protein function in disease; greater understanding of medicinal and organic chemistry in drug design, drug targeting, mechanisms and effectiveness of drug action; patentable methods and bioactive compounds; and new experimental leads to new medicines for development towards the clinic.

The physiological role and therapeutic potential of gut peptides modulating appetite

Principal Advisor: A/Prof Markus Muttenthaler (m.muttenthaler@imb.uq.edu.au)

Associate Advisor: Dr. Sebastian Furness (SBMS, s.furness@uq.edu.au)

The advent of highly processed, calorie-rich foods in combination with increasingly sedentary lifestyles has seen a rapid rise in overweight and obesity. 60–80% of populations in developed countries are overweight or obese, and over three million deaths each year are attributed to a high body mass index. Obesity is also a risk factor for diabetes, hypertension, cardiovascular disease, kidney disease and cancer. This has a clear impact on life expectancy, with predictions that this generation will be the first to have a shorter life expectancy than the last. Despite this enormous socio-economic impact, treatment options are limited.

Our research groups are interested in the role of the gut peptides GLP-1 and CCK in regulating appetite and satiety. A subset of GLP-1 mimetics are already successful treatments for obesity; however, compliance is low as they are injectables. The project will focus on the development of orally active mimetics. The project will also develop molecular probes to facilitate the study of the GLP1 and CCK1 receptors in the context of appetite regulation across the gut-brain axis.

The candidate should have a degree in chemistry, biochemistry or pharmacology, good hands-on laboratory skills, and a desire to drive the project. The candidate will be involved in solid phase peptide synthesis, medicinal chemistry, mass spectrometry, structure-activity relationship studies, cell culture, gut stability assays, cell signalling and receptor pharmacology.

Towards the sustainable discovery and development of new antibiotics

Principal Advisor: Dr Zeinab Khalil (z.khalil@uq.edu.au)

Associate Advisor: Dr Angela Salim (a.salim@imb.uq.edu.au), Professor Rob Capon (r.capon@imb.uq.edu.au) and Professor Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

The worldwide emergence and relentless escalation of antibiotic drug resistance (i.e. methicillin-resistant Staphylococcus aureus) have demanded ongoing commitment over decades to discovering new antimicrobial weapons.1 Yet, even with the widespread acceptance of the need for new antibiotics in both the scientific community and the public at large, an urgent need for new approaches remains. Fortunately, microorganisms continue to produce their own wealth of structurally diverse and highly specialised metabolites, each with a remarkable range of biological activities that in themselves could present the next antibiotic breakthrough.

Microbial genomes are rich in silent biosynthetic gene clusters (BGCs), encoding for defensive agents (i.e. antibiotics) that fail to express in standard laboratory monoculture conditions, presumably due to the paucity of environmental cues. Nitric oxide (NO) is well known for its regulatory role in mammalian and plant biology, little is known about its role in regulating microbial silent BGCs. We revealed Nitric Oxide Mediated Transcriptional Activation (NOMETA) as a potentially cost-effective & rapid approach for an in situ (i.e. non-genome mining) approach to accessing the valuable chemistry encoded within microbial silent BGCs.

This project will deliver two key solutions to the major problem of AMR: (i) develop an innovative method that applies NO to activate the transcription of microbial silent BGCs to access new defensive agents capable of informing the development of new antibiotic classes, and (ii) apply new genomic and metabolomics data mining technologies for microbes identified in our Soils for Science citizen science program to identify additional antibiotics for future drug development.

Join our collaborative team as we explore the frontiers of analytical, spectroscopic, and medicinal chemistry, guided by the expertise of microbiological and genomic sciences. Together, we are on the verge of unveiling the mysteries of nature, paving the way for groundbreaking discoveries in the antibiotic drug discovery.

Tuning the activating stimulus of voltage-gated sodium channels

Principal Advisor: Dr Angelo Keramidas (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

This project will investigate how voltage-gated sodium channels, which are proteins (ion channels) found on the surface of neurons (brain cells and nerves) function as molecular conduits of cell-to-cell electrical communication. The overall aim is to study how molecular probes (venom peptides) and structural parts of these ion channels affect the local biophysical environment of the ion channels, and how this leads to fine tuning of the ion channel's sensitivity to the stimulus that activates them (cell membrane voltage).

This project will use natural and modified peptides that are derived from venoms of different species, such as spiders and ants to probe and manipulate the functional properties of an ion channel that is critically important to the function of the nervous system.

The conceptual knowledge gained from this project would advance our understanding of a fundamental physiological process and facilitate the development of drugs that regulate ion channel function, such as antiepileptics, analgesics and insecticides.

Understanding how blood vessels in the brain are formed

Principal Advisor: Dr Rosemary Cater (r.cater@uq.edu.au)

Associate Advisor: Dr Anne Lagendijk (a.lagendijk@imb.uq.edu.au)

The human brain comprises ~650 kilometres of blood vessels lined by brain endothelial cells, which supply the brain with oxygen and essential nutrients. The growth of cerebral blood vessels begins early in development via a process called sprouting angiogenesis. Despite its importance, the molecular mechanisms underlying brain angiogenesis and formation of the blood-brain barrier are poorly understood. It has recently been demonstrated that the gene Flvcr2 is critical for blood vessels to grow in the brain, and last year we discovered that the protein encoded by this gene (FLVCR2) transports choline – an essential nutrient – across the blood brain barrier and into the brain. This project will utilise biochemical techniques and structural biology (cryo-EM) to investigate what other molecules may regulate this transport process, and how choline regulates angiogenesis in the brain.

Using transposon sequencing to probe whole cell protein-protein interactions inside the bacterial cell

Principal Advisor: Dr Emily Goodall (IMB)

Associate Advisor: Prof Ben Hankerman (IMB); Prof Ian Henderson (IMB)

Friend or Foe, bacteria are powerhouses at the centre of many important biotechnological processes, but also the disease-causing agents of many infectious diseases. Understanding the fundamental processes of a bacterial cell is key to understanding (1) how to harness these organisms for biotechnological gain and (2) how to target them in the treatment of an infection. Using the model organism, Escherichia coli, we aim to develop a method for identifying protein-protein interactions in a high throughput format. The methodology developed in this project will enable total proteome screening and has implications for studying both fundamental cell physiology as well as the potential for studying protein-drug interactions in vivo. After development, the technology will be validated by screening for chemical inhibitors of protein-protein interactions.

Venom-derived drugs for targeting ion channels involved in genetic epilepsies

Principal Advisor: Prof Glenn King (IMB)

Associate Advisor: A/Prof Lata Vadlamudi (UQ Centre for Clinical Research)

There are more than 65 million people currently living with epilepsy, and more than 1/3 are resistant to anti-seizure medications (ASMs). For these latter patients, new efficacious ASMs are urgently required. This project will focus on development of biologic drugs for treatment of genetic epilepsies caused by aberrant expression of a voltage-gated ion channel. We are specifically interested in: (i) Dravet syndrome, which is caused by aberrant function of the voltage-gated sodium channel Nav1.1, and (ii) KCNH1 epilepsy, caused by gain-of-function mutations in the voltage-gated potassium channel Kv10.1, which was first described here at the Institute for Molecular Bioscience. This project brings together the expertise of the King lab in venoms-based peptide-drug discovery and development, and the clinical expertise of Prof. Vadlamudi in treatment of genetic epilepsies. Lead compounds will be isolated from arthropod venoms, the best known source of ion channel modulators. Prof. King’s lab has access to the largest collection of arthropod venoms in the world (>500 species). Lead compounds will be tested in brain organoids produced from patient-derived stem cells as well as in vivo rodent models of Dravet syndrome and KCNH1 epilepsy.

Venom-derived ion channel inhibitors as novel neuroprotective drugs for neurodegenerative diseases

Principal Advisor: Dr Fernanda C Cardoso (IMB)

Associate Advisor: Dr Jean Giacomotto (QBI/Griffith); Prof Glenn King (IMB)

Neurodegenerative diseases are caused by progressive loss of neurons, leading to dementia, motor dysfunction, paralysis, and death. Investigation of ion channels in central neurons unravelled clusters of voltage-gated ion channel subtypes playing a key pathological role in the pre-symptomatic stages of neurodegenerative diseases. Venoms are an exceptional source of peptides modulating ion channels with higher potency and selectivity than poorly efficacious drugs used in the treatment of neurodegeneration.
This project involves systematically interrogating venoms using computational approaches, high throughput in vitro and in vivo screens, venomics and pharmacology to discover venom peptides that selectively modulate ion channels in central neurons and therefore have the potential to prevent central neurodegeneration.
This is a multidisciplinary project in drug discovery utilizing venoms and other natural repertoires as main sources of bio-active molecules. PhD scholars will develop skills in computational biology, manual and automated whole-cell patch clamp electrophysiology, ex vivo tissue electrophysiology, in vivo screen in zebrafish, high performance liquid chromatography, mass spectrometry, recombinant expression, peptide synthesis, amongst other state-of-the-art methods and techniques. Students will author papers and be involved in writing and preparation of figures for research publications from their work.

Venom-derived peptides as novel analgesic leads

Principal Advisor: Prof Irina Vetter IMB)

Associate Advisor: Dr Richard Clark (UQ School of Biomedical Sciences)

Voltage-gated sodium channels are well-validated analgesic targets, with loss-of-function mutations leading to an inability to sense pain, but otherwise normal physiology and sensations. However, efforts to mirror these genetic phenotypes with small molecule inhibitors have highlighted that both selectivity over ion channel subtypes and mechanism of action are key considerations for the development of safe and effective analgesics.

This project will leverage the exquisite potency and selectivity of peptide sodium channel modulators from venoms for the rational development of novel, safe and effective molecules with analgesic activity.

Students will gain experience with peptide synthesis, patch-clamp electrophysiology, sensory neuron culture, microscopy and in vivo behavioural assays to tackle the global problem of unrelieved chronic pain with innovative molecules targeting peripheral sensory neuron function.

Antibiotic Conjugates: Joining Hands to Combat AMR

Principal Advisor: A/Prof Mark Blaskovich (IMB)

Associate Advisor: Dr Anthony Verderosa (IMB)

The world is running out of effective antibiotics, which underpin modern medicine. Antimicrobial resistance is threatening a return to a pre-antibiotic era, when simple cuts and scrapes can be deadly. This project is based on a platform developed over multiple years, where existing and new antibiotics are functionalised so that they can be readily modified. We then use this handle to attach useful functionality, including fluorophores and other imaging agents to detect bacteria, or adjuvants and immune stimulators to help kill them. These includes PROTAC (proteolysis targeting chimera), ARMS (Antibody-recruiting molecule) and ADC (antibody-drug conjugate) approaches. We are particularly interested in chemists with a strong synthetic chemistry background and an interest in learning medicinal chemistry, as the antibiotics cover multiple types of chemical scaffolds (peptide, carbohydrates, heteroaromatics, macrocycles) and can require multistep synthetic strategies.

Boosting innate immune defence to combat antibiotic-resistant bacterial infections

Principal Advisor: Prof Matt Sweet (IMB)

Associate Advisor: Prof Mark Schembri (IMB)

For bacterial pathogens to colonise the host and cause disease, they must first overcome frontline defence of the innate immune system. Innate immune cells such as macrophages engage a suite of direct antimicrobial responses to destroy engulfed bacteria, including free radical attack, lysosomal degradation, nutrient starvation, metal ion poisoning, and lipid droplet-mediated delivery of antimicrobial proteins. A detailed understanding of such pathways can provide opportunities to manipulate macrophage functions to combat antibiotic-resistant bacterial infections. This project will explore the regulation of specific macrophage antimicrobial responses, with the goal of manipulating the functions of these cells to combat infections caused by uropathogenic E. coli, a major cause of urinary tract infections and sepsis.

Genetics of biofilms

Principal Advisor: Prof Mark Schembri (m.schembri@uq.edu.au)

Associate Advisors: Dr Nhu Nguyen (kn.nguyen@uq.edu.au) and Dr Zack Lian (IMB; z.lian@uq.edu.au)

Biofilms are surface-attached clusters of bacteria encased in an extracellular matrix and are significantly associated with increased antibiotic resistance. This project will apply molecular microbiology methods to understand the structure, function and regulation of biofilms produced by uropathogenic E. coli that cause urinary tract infections, and investigate new strategies to disrupt biofilms. The project will build skills in cutting edge genetic screens, molecular microbiology, genome sequencing, bioinformatics, microscopy, imaging and animal infection models. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

How antibiotic resistant bacteria cause urinary tract infection

Principal Advisor: Prof Mark Schembri (IMB)

Associate Advisor: Prof Matt Sweet (IMB)

Urinary tract infections (UTIs) are one of the most common infectious diseases, with a global annual incidence of ~175M cases. UTI is also a major precursor to sepsis, which affects ~50M people worldwide each year, with a mortality rate of 20-40% in developed countries. Uropathogenic E. coli (UPEC) is the major cause of UTI and a leading cause of sepsis. The last decade has seen an unprecedented rise in antibiotic resistance among UPEC, resulting in high rates of treatment failure and mounting pressure on healthcare systems. This project will explore how UPEC cause disease and become resistant to antibiotics, with a goal to identify new approaches to treat and prevent infection.

How bacteria cause severe life-threatening infections in infants

Principal Advisor: Prof Mark Schembri (IMB)

Associate Advisor: A/Prof Adam Irwin (UQ Centre for Clinical Research)

Neonatal meningitis is a devasting disease with high rates of mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis and the most common cause of meningitis in preterm neonates. Despite this, we have limited knowledge about the global epidemiology of E. coli that cause neonatal meningitis, genomic relationships between different strains, and mechanisms that enable E. coli to cause severe infection in new-born infants. This project will identify and characterise common genomic features of E. coli that cause neonatal meningitis, and employ molecular microbiology methods in conjunction with animal models to understand disease pathogenesis and antibiotic resistance. Our goal is to develop new diagnostic and therapeutic interventions to prevent this life-threatening disease.

How bacteria form antibiotic resistant biofilms

Principal Advisor: Prof Mark Schembri (IMB)

Associate Advisors: A/Prof Markus Muttenthaler, Prof Waldemar Vollmer (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

Biofilms are surface-attached clusters of bacteria encased in an extracellular matrix. They are a significant problem in many areas that influence our everyday life, including agriculture (e.g. plant and animal infections), industry (e.g. contamination of plumbing, ventilation and food industry surfaces) and medicine (e.g. ~80% of human infections are biofilm associated, including device-related infections). This project will apply molecular microbiology methodsto understand the structure, function and regulation of biofilms produced by uropathogenic E. coli that cause urinary tract infections, and investigate new strategies to disrupt biofilms. The project will build skills in cutting edge genetic screens, molecular microbiology, genome sequencing, bioinformatics, microscopy, imaging and animal infection models. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

How bacteria fortify their cell envelope under stress

Principal Advisor: Professor Waldemar Vollmer (w.vollmer@uq.edu.au)

Associate Advisor: Prof Mark Schembri (m.schembri@uq.edu.au)

Gram-negative bacteria use some of their most abundant cellular proteins connect the outer membrane with the underlying cell wall (peptidoglycan) layer and this tight connection protects the cell from many toxic molecules and even antibiotics. However, most of the known peptidoglycan-interacting proteins are poorly characterised and we lack a comprehensive inventory of these proteins and their functions in key pathogens. In this project, the PhD student will develop novel proteomics approaches to identify all peptidoglycan-bound proteins in important Gram-negative pathogens, and then identify peptidoglycan-interacting proteins that fortify the cell envelope when bacteria encounter host defence factors and antibiotics. In addition to state-of-the art molecular biology and high-throughput microbiology screening techniques, the student will use cell biology and biochemical methodologies to gain understanding of the cellular roles of new cell envelope proteins identified. The student will benefit from working in an outstanding research environment and in research groups with a strong expertise in bacterial cell envelope biology and pathogenicity. The expected outcomes will be important to develop new strategies to fight infections caused by antibiotic resistant bacteria.

How does innate immune signalling combat influenza in birds?

Principal Advisor: Dr Larisa Labzin (IMB)

Associate Advisor: A/Prof Kirsty Short (UQ School of Chemistry and Molecular Biosciences)

Emerging viruses such as Highly Pathogenic Avian Influenza, HPAIV and SARS-CoV-2 can cause deadly outbreaks that decimate wild and domestic animal populations or cause global pandemics. . Some species, particularly bats and wild birds, can carry these viruses with minimal disease, meaning they can easily spread viruses between farms, states and even countries. The immune response is the best protection against viral infection, yet in susceptible species (such as chickens and pigs), immune overactivation may cause collateral tissue damage, driving disease pathology. This PhD project will study how the immune systems of different species recognise viral infections. This research will determine if viral reservoir species (such as ducks and bats) mount a specific kind of immune response that allows them to tolerate viruses, which is distinct to susceptible species (such as chickens and pigs). This project will utilise cell biology, imaging, molecular cloning, and virology to identify new ways to prevent pandemic virus outbreaks and protect vulnerable species.

Identifying new targets for treatment of antimicrobial resistant infections

Principal Advisor: Prof Ian Henderson (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

Driven by the introduction of antibiotics and vaccines, deaths from infectious diseases declined markedly during the 20th century. These unprecedented interventions paved the way for other medical treatments; cancer chemotherapy and major surgery would not be possible without effective antibiotics to prevent and treat bacterial infections. The evolution and widespread distribution of antibiotic-resistance elements, and the lack of new antimicrobials, threatens the last century of medical advances; without action the annual death toll from drug-resistant infections will increase from 0.5 million in 2016 to 10 million by 2050. New treatments are desperately needed including new antibiotics and alternative treatments such as phage. This project will address the molecular basis for the basis of phage interaction with the bacterial cell envelope and the potential for using this knowledge to treat antibiotic resistant infections.

Large-scale genomic and functional analysis of the bacterial cell envelope to identify new targets for antibiotics

Principal Advisor: Professor Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

Associate Advisor: Dr Brian Forde (b.forde@uq.edu.au); Dr Rudi Sullivan (rudi.sullivan@imb.uq.edu.au)

The current spread of antimicrobial resistance is a major concern for public health because the pipeline of antibiotic drug development is almost empty. Hence, there is an urgent need to discover new ways to inhibit and kill disease-causing bacteria by new drugs to be developed. The bacterial cell wall envelope is an ideal target for antibiotics because it is essential for a bacterial cell and not present in humans, and target sites are better accessible for drugs than internal ones. Indeed, some of the most successful antibiotics in history (e.g., the beta-lactams) inhibit bacterial cell wall synthesis. The PhD student will generate a web-based platform of the cell envelope proteins encoded in the available genomes of thousands of bacterial strains and species, and perform bioinformatic analysis of the distribution and abundance of key essential proteins of cell envelope biogenesis, to predict promising new target sites for antibiotic action (computational part). The PhD student will then validate selected target sites identified, using genetic and molecular biology methodologies in important bacterial pathogens (experimental part). The focus will be to identify new targets present in bacteria that are resistant to known antibiotics, aiming to discover new mechanisms to kill pathogenic bacteria.

Molecular Immunology of Malaria

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Prof Gabrielle Belz (Frazer Institute)

An opportunity exists for a PhD position in the molecular immunology of malaria. The focus of this project will be to apply cutting-edge technologies to understand the molecular basis of protective immunity to malaria. It will take advantage of controlled human infection models and as well as animal models to explore the mechanisms underlying protective immunity to malaria and immune responsiveness. Using a range of interdisciplinary approaches including immune profiling, transcriptomics, proteomics, and small molecule characterization, the project aims to define the critical cells and signalling pathways required for protective immunity against malaria. It is anticipated that this research will have broad application to a wide range of infectious and chronic diseases, with important implications for vaccination.

Subject areas: Immunology, Molecular immunology, Systems biology, Vaccinology, Malaria

Eligibility: Entry: Bachelor degree with Honours Class I (or equivalent via outstanding record of professional or research achievements). Experience/Background: laboratory-based experience in immunology, host-pathogen interactions, immune regulation and infectious diseases; excellent computer, communication, and organisational skills are required.

Novel assays for antibiotic discovery

Principal Advisor: Prof Waldemar Vollmer (IMB)

Associate Advisor: Mr Alun Jones (IMB); Prof Rob Capon (IMB)

The PhD project addresses the global burden of Antimicrobial Drug Resistance (AMR) by developing new assays for antibiotic discovery. The bacterial cell wall is targeted by some of our best antibiotics (e.g., beta-lactams, glycopeptides) and remains an attractive target for antibiotic drug discovery. Our group investigates the molecular mechanisms underpinning cell wall synthesis during growth and division of a bacterial cell. We pioneered the development of biochemical assays to monitor the activities and interactions of essential enzymes required for the synthesis of peptidoglycan, identified the first activators of peptidoglycan synthases and deciphered the activation mechanism. The PGR student will be trained in a wide range of molecular biology, (analytical) biochemistry and bacterial cell biology techniques and use these to develop innovative assay for key peptidoglycan enzymes that built and remodel the cell wall in pathogenic bacteria. The PGR student will then use the new assays to screen compound libraries to identify inhibitors. Hit compounds will be characterised by cellular and biochemical techniques and assessed for their potential to be developed into new antibiotics.

Systems immunology and multi-omics approaches to understand protective immunity to human malaria

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Dr Carla Prioetti (IMB); A/Prof Jessica Mar (AIBN)

This PhD project aims to develop and apply computational approaches that integrate systems biology and molecular immunology to understand host-pathogen immunity and predict immune control of malaria. The project will utilise systems-based immunology and multi-omics approaches to profile the host immune response in controlled infection models of malaria at molecular, cellular, transcriptome and proteome-wide scale.

The overall aim will be to develop and apply omics-based technologies and computational tools, including network theory and machine learning, to integrate multiple high-dimensional datasets and reveal novel insights into host-pathogen immunity and predict immune responsiveness and parasite control. Modelling of large-scale existing datasets, including those generated by single-cell RNA-sequencing technologies, may also be a feature of this project. The opportunity to identify new knowledge and integrate this with experimental data produced by our laboratory will be instrumental to extending the impact of these bioinformatics analyses. This project will provide an opportunity to be at the forefront in cutting-edge technologies and advances in computational analysis of integrated high-dimensional omic data.

Eligibility:

Entry: BSc Honours Class I (or equivalent via outstanding record of professional or research achievements)
Experience/Background: Experience with programming languages, mathematics, statistics and/or background in immunology and molecular sciences, with an interest in integrating the fields of immunology and bioinformatics.

Excellent computer, communication, and organisational skills are required. Forward thinking, innovation and creativity are encouraged.

Targeting the bacterial cell wall for antibiotic drug discovery

Principal Advisor: Prof Waldemar Vollmer (w.vollmer@imb.uq.edu.au)

Associate Advisors: Prof Rob Capon (IMB); Dr Zeinab Khalil (IMB); Dr Alun Jones (IMB); Dr Rudi Sullivan (IMB)

References:
1. Egan et al. 2020. Regulation of peptidoglycan synthesis and remodelling. Nature Reviews Microbiology 18, 446–460.
2. Oluwole et al. 2022. Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients. Nature Communications 13:2278.

The application of metagenomics to clinical microbiology and infection control

Principal Advisor: Dr Brian Forde (b.forde@uq.edu.au)

Associate Advisors: Dr Patrick Harris (UQCCR, p.harris@uq.edu.au), Dr Kym Lowry (UQCCR, k.lowry@uq.edu.au)

Hospital-acquired infections (HAIs) present significant healthcare challenges globally, affecting patients in both developed and developing nations. In Australia alone, over 165,000 patients suffer from HAIs annually, with antimicrobial resistance (AMR) compounding the issue by limiting treatment options and worsening patient outcomes. Prospective whole-genome sequencing (WGS) has emerged as an optimal approach for rapidly identifying transmission of multi-drug resistant (MDR) bacteria. However, current surveillance methods primarily rely on culture-based isolation of specific pathogens, followed by detailed genomics characterisation of individuals, which is labour-intensive, prone to selection bias, and fails to provide insights into community dynamics and interactions between patients and the hospital environment. This project aims to pioneer an alternative approach: prospective metagenomic surveillance. By leveraging high-throughput metagenomics, this project seeks to profile overall community structure, characterise community dynamics, and identify and control pathogen transmission in clinical settings. The research will involve developing new workflows and pipelines to integrate metagenomic surveillance into routine clinical practice, thereby enhancing infection control strategies and patient care

Understanding antibiotic resistance

Principal Advisor: Prof Mark Schembri (m.schembri@uq.edu.au)

Associate Advisor: Dr Brian Forde (b.forde@uq.edu.au), Dr Patrick Harris (UQCCR; p.harris@uq.edu.au), Dr Minh-Duy Phan (IMB; m.phan1@uq.edu.au)

Antimicrobial resistance (AMR) is a major threat to global human health. In 2019 alone, there were an estimated 4.95 million deaths associated with bacterial AMR, with uropathogenic E. coli (UPEC) a leading pathogen associated with urinary tract infections, sepsis and high rates of antibiotic resistance. This project will use cutting edge genetic screens, molecular microbiology, genome sequencing and bioinformatics to understand how plasmids contribute to the spread of antibiotic resistance in UPEC. Students with an interest in microbiology, bacterial pathogenesis and antibiotic resistance are encouraged to apply.

Understanding the link between EBV and Multiple Sclerosis

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Dr Carla Prioetti (IMB)

An opportunity exists for a PhD position in molecular immunology, where cutting-edge technologies will be applied to understand the molecular basis of the link between EBV and Multiple Sclerosis. Epstein-Barr virus (EBV) is the top identified causative agent of Multiple Sclerosis, but how this occurs is not known. This project aims to apply an innovative approach using proteome-wide screening of EBV to identify the subset of EBV proteins from the complete EBV proteome that triggers MS. It will compare responses in individuals with different stages of MS and apply sophisticated computational analytics to identify specific EBV proteins that predict MS disease. This EBV signature of MS could be translated into a clinic-friendly point-of-care test. If successful, this project could revolutionize the diagnosis and management of MS, providing patients with a quicker and more accurate diagnosis and enhanced quality of life.

Eligibility:
Entry: Bachelor degree with Honours Class I (or equivalent via outstanding record of professional or research achievements)
Experience/Background: laboratory-based experience in immunology, host-pathogen interactions, immune regulation and infectious diseases; excellent computer, communication, and organisational skills are required.

Understanding the role of lipids in inflammation and immune clearance of pathogens

Principal Advisor: Dr Jessica Rooke (IMB)

Associate Advisor: Prof Ian Henderson (IMB); Prof Matt Sweet (IMB)

Salmonella enterica is a broad host range pathogen that is distributed globally. Worryingly, S. enterica strains are becoming increasingly resistant to routinely used antibiotics, leading to the World Health Organisation classifying S. enterica as a high priority pathogen for which alternative treatments are desperately needed. By understanding how Salmonellainfects a host, novel therapies and vaccines can be designed to prevent disease. Recent evidence suggests that pathogen-lipid interactions are important for pathogens to survive in the host and that Salmonella has a unique, conserved lipase that is essential for these interactions. This project aims to establish the molecular mechanism by which Salmonella interacts with host lipids to enable evasion and manipulation of host immune responses. These investigations will provide novel insights into fundamental Salmonella biology and aid in the development of more effective strategies to treat Salmonella infections, such as novel drug targets and/or novel vaccine candidates.

Vaccine Engineering

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Dr Carla Prioetti (IMB)

An opportunity exists for a PhD position in vaccine engineering. Vaccines are one of the most effective health care interventions but remain a challenge for many diseases, and in particular intracellular pathogens such as malaria where T cell responses are particularly desirable. We have been exploring novel approaches to rationally design an effective vaccine against challenging disease targets. By taking advantage of recent advances in genomic sequencing, proteomics, transcriptional profiling, and molecular immunology, we have discovered unique targets of T cell responses or antibody response. This project will test these antigens as vaccine candidates by assessing immunogenicity, protective capacity and biological function using different vaccine platforms. By designing an effective vaccine from genomic data, this project is expected to result in significance advances in vaccinology as well as immunology, with important public health outcomes.

Eligibility:

Entry: Bachelor degree with Honours Class I (or equivalent via outstanding record of professional or research achievements)
Experience/Background: laboratory-based experience in immunology, host-pathogen interactions, immune regulation and infectious diseases; excellent computer, communication, and organisational skills are required.

Gender matters: Using genomic data to understand sex-specific risk in heart disease

Principal Advisor: Dr Sonia Shah (IMB)

Associate Advisor: Prof Gita Mishra (UQ School of Public Health)

The 2019 Women and Heart Disease forum highlighted clear disparities in CVD outcomes between males and females. The report (Arnott et al 2019 Heart, Lung and Circulation), highlighted a need to increase our understanding of sex-specific pathophysiology driving susceptibility to common diseases, and identification of sex-specific risk factors to improve early detection and prevention of CVD in women. Until recently, sex-specific research was underpowered and most studies on heart disease included a much smaller number of female participants. But this is beginning to change with the availability of large biobank data.

This project will require statistical analysis of very large datasets with health records linked to genomic data to address these gaps in our understanding of heart disease in women. This includes data from the UK Biobank cohort in ~500,000 individuals (54% women) and data from the Australian Women’s Longitudinal Study (led by Prof Gita Mishra), a study looking at the factors contributing to the health and wellbeing of over 57,000 Australian women, and is the largest, longest-running project of its kind ever conducted in Australia.

This project will lead to a better understanding of sex-specific risk factors for CVD, which will inform better CVD prevention strategies in women.

Genetics of sensory nutrition – using genetics to understand how taste and olfactory perception influences eating behaviour and health

Principal Advisor: Dr Daniel Hwang (IMB)

This project requires candidates to commence no later than Research Quarter 3, 2025, which means you must apply no later than 29 February 2024.

Human perception of taste and smell plays a key role in food preferences and choices. There is a large and growing body of work suggesting that taste and smell (together known as "chemosensory perception") determine eating behaviour and dietary intake, a primary risk factor of chronic conditions such as obesity, cardiometabolic disorders, and cancer.

However, evidence to date is largely based on observational studies that are susceptible to confounding and reverse causation, leaving the "causal effects" of chemosensory perception on food consumption unclear. If their relationship is truly causal, flavour modification may represent a tangible way of modifying food consumption in a way that benefits public health outcomes.

This PhD project aims to: (i) elucidate the genetic architecture underlying individual differences in taste and smell perception, (ii) use this information to assess their causal effects on eating behaviour, and (iii) create a sensory-food causal network mapping individual sensory qualities (i.e. sweet taste, bitter taste, and more) to individual food items.

The candidate will gain skills in big data analyses, computer programming, statistical method development and application (structural equation modelling, genome-wide association analysis, Mendelian randomisation), and writing and publishing scientific peer-reviewed papers. The candidate will also have opportunities to be involved and to lead national and international collaborative projects.

Genomics of Caveolae Disease

Principal Advisor: Dr Allan McRae (IMB)

Associate Advisor: Prof Robert Parton (IMB)

Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. Loss or mutation of genes involved in caveolae have shown to cause disease including lipodystrophy and pulmonary arterial hypertension. This project will ustilise publicly available genomic data to further explore the role of genetic variation in caveole genes in disease.

Harnessing biobank information to understand Motor Neuron Disease

Principal Advisor: Dr Allan McRae (IMB)

Associate Advisor: Dr Fleur Garton (IMB), A/Prof Robert Henderson (UQ Centre for Clinical Research)

Motor neuron disease results in the degeneration of the motor neurons leading to paralysis and death. There is limited knowledge on the underlying causes and no treatment can significantly change the fatal course of the disease. Slowing the discovery process has been the limited, clinic-based sample sizes. At least three large international biobank datasets, with matched genotype and phenotype data are now available and more are anticipated. The large sample provides a powerful opportunity to investigate this complex disease. Our group has expertise in harnessing large datasets such as the UK Biobank to answer questions about complex traits and diseases. This project will aim to integrate multiple international biobank datasets to better understand the disease and avenues for treatment.

Leveraging high-throughput genetic screens to evolve the power of algae in biotechnology

Principal Advisor: Prof Ben Hankamer

Associate Advisor: Prof Ian Henderson

Algae cells have evolved over ~3 billion years of natural selection to yield a diverse array of highly efficient, self-assembling, light-responsive membranes. These act as Nature’s solar interfaces, via which plants tap into the power of the sun. These interfaces contain nano-machinery to drive the photosynthetic light reactions which convert light from the sun into food, fuel, and atmospheric oxygen to support life on Earth. However, microalgae can be used to produce foods/nutraceuticals, vaccines, peptide therapeutics, novel antibiotics, fuel, and bioremediation. While much successful work has been done to improve the use of algae, the genetics of the various species are not well understood. Here we will deploy a high through put genetic approach to identify essential and conditionally-essential genes in algae providing insight into the fundamental biology of these organisms. We will leverage this approach to forcibly evolve algae and improve recombinant protein production.

Parsing the genome into functional units to understand the genetic basis of cell identity and function

Principal Advisor: Associate Professor Nathan Palpant (n.palpant@uq.edu.au)

Associate Advisors: Dr Woo Jun Shim (w.shim@uq.edu.au), Dr Sonia Shah (sonia.shah@imb.uq.edu.au), Dr Bastien Llamas (University of Adelaide)

The billions of bases in the genome are shared among all cell types and tissues in the body. Understanding how regions of the genome control the diverse functions of cells is fundamental to understanding evolution, development, and disease. We recently identified approaches to define diverse biologically constrained regions of the genome that appear to control very specific cellular functions. This project will evaluate how these biologically constrained regions of the genome have influenced evolutionary processes, evaluate their regulatory basis in controlling the identity and function of cells, and analyse the promiscuity of cross-talk between different biologically constrained regions. The project will also study how these genomic regions impact disease mechanisms by evaluating how disease-associated variants in different regions influence survival of patients with cancer and assessing whether these regions are associated with identifying causal disease variants in human complex trait data. The project will involve significant collaborative work with industry partners and researchers across Australia with the goal of providing critical insights into fundamental mechanisms of genome regulation.

Sometimes Correlation does Equal Causation: Developing Statistical Methods to Determine Causality Using Genetic Data

Principal Advisor: Prof David Evans (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

There is a well-known mantra that correlation does not necessarily equal causation. This is why randomized controlled trials in which participants are physically randomized into treatment and placebo groups are the gold standard for assessing causality in epidemiological investigations. However, what is less appreciated is that strong evidence for causality can sometimes be obtained using observational data only. In particular, genotypes are randomly transmitted from parents to their offspring independent of the environment and other confounding factors, meaning that genotypes associated with particular traits can be used like natural “randomized controlled trials” to examine whether these traits causally affect risk of disease.

The aim of this PhD project is to develop statistical methods to assess causality using observational data alone. The successful candidate will gain experience across a wide range of advanced statistical genetics methodologies including Mendelian randomization (a way of using genetic variants to investigate putatively causal relationships), structural equation modelling, genome-wide association analysis (GWAS), genetic restricted maximum likelihood (G-REML) analysis of genome-wide data which can be used to partition variation in phenotypes into genetic and environmental sources of variation, and instrumental variables analysis (using natural “experiments” to obtain information on causality from observational data). The candidate will apply the new statistical methods that they develop to large genetically informative datasets like the UK Biobank (500,000 individuals with genome-wide SNP data).

Systems immunology and multi-omics approaches to understand protective immunity to human malaria

Principal Advisor: Prof Denise Doolan (IMB)

Associate Advisor: Dr Carla Proietti (IMB); Dr Jessica Mar (AIBN)

We invite applications for a PhD position focused on identifying human host factors that predict immune control of malaria. The project will utilise systems-based immunology and multi-omics approaches to profile the host immune response in controlled infection models of malaria at molecular, cellular, transcriptome and proteome-wide scale. The overall aim will be to develop and apply computational approaches, including network theory and machine learning, which integrate systems biology and molecular immunology to understand host-pathogen immunity and predict immune responsiveness and parasite control. Modelling of largescale existing datasets, including those generated by single cell RNA-sequencing technologies, may also be a feature of this project. The opportunity to identify new knowledge and integrate this with experimental data produced by our laboratory will be instrumental to extending the impact of these bioinformatics analyses. This project will provide an opportunity to be involved in cutting-edge advances integrating diverse fields of high dimensional omic datasets to inform the development of vaccines, immunotherapies or diagnostic biomarkers.

Methodologies: Bioinformatics, Machine Learning, Immunology, Systems Immunology, Systems Biology, Genomics/Proteomics/Transcriptomics, Molecular and Cell Biology, Statistics

Eligibility: Entry: BSc Honours Class I (or equivalent via outstanding record of professional or research achievements)
Experience/Background: Experience with programming languages, mathematics, statistics and/or background in immunology and molecular sciences, with an interest in integrating the fields of immunology and bioinformatics. Excellent computer, communication, and organisational skills are required. Forward thinking, innovation and creativity are encouraged.

Testing effect of environmental exposures on subsequent human generations

Principal Advisor: Dr Gunn-Helen Moen (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

We are seeking a PhD candidate to join our research team in this exciting project funded by the Australian Research Council. The research group has conducted work within genetic epidemiology, focusing on pregnancy related exposures and outcomes.

Depending on the student’s level of experience and aptitude, they will help develop and/or apply statistical genetics approaches to investigate the possible existence of transgenerational epigenetic effects on human phenotypes.

A PhD is about learning new skills and learning how to do research. Our ideal candidate will have knowledge or keen interest in learning genetics, epidemiology, statistics, unix and shell scripting, and statistical software such as R. You will work closely with an experienced researcher on the project. There will also be possibility for a research stay in Norway during this PhD.

The main purpose of the fellowship is research training leading to the successful completion of a PhD degree.

The advertised projects are fundamentally quantitative and computer-based, and so evidence of aptitude in these areas is essential. The candidate should also have the ability to design, plan, and execute experiments and be proficient in English, both written and oral.

We are looking for someone who is:

Excellent communication and team working skills
Organized and structured
Flexible
Enthusiastic and willing to learn new methods and techniques

Understanding the genetic and phenotypic basis of rare disease variants

Principal Advisor: Associate Professor Nathan Palpant (n.palpant@uq.edu.au)

Associate Advisors: Dr Sonia Shah (sonia.shah@imb.uq.edu.au) and Dr Mikael Boden (SCMB)

Genome sequencing is a powerful tool for studying the biological basis of disease, yet out of millions of data points, finding the underlying cause of disease can be difficult. Current protocols for classifying variants from patient DNA data largely rely on prior knowledge about normal and abnormal gene variation contained in large public databases, known disease-causing gene panels, or identifying variants causing amino acid changes in proteins (which only comprise 2% of the genome). Despite these powerful approaches, studies indicate that classifying variants as pathogenic occurs in only a minority of cases and among variants reported in ClinVar, a public archive of relationships between human variation and phenotype, wherein a large proportion (37%) are classified as variants of unknown significance (VUS). This project aims to address this key gap in knowledge, involving work in computational and/or cell biology studies, depending on the student skills and interests. For computational studies, this project aims to develop methods that integrate predictive, genome-wide identifiers of pathogenicity. We will use machine learning to build non-linear prediction methods that outperform individual prediction tools in identifying genetic causes of disease and accelerating clinical diagnosis of genetic diseases. For cell biology studies, we aim to use clinical genetics data (from the Australian Functional Genomics Network) to determine pathogenicity of variants from patients with inherited cardiovascular diseases. The approaches will include: 1) cell modelling with human pluripotent stem cells (hPSCs), a disease-agnostic and scalable platform for high-throughput hPSC variant screening. To study variants in genes such as transcription factors that are known to cause genetic diseases, we will use molecular phenotyping by genome-wide proximity labelling with DNA adenine methyltransferase (DamID) to study how disease-causing variants alter regulatory control of the genome. Collectively, this aim implements computational predictions with disease modelling as an efficient, scalable, and disease agnostic pipeline to increase the diagnostic rate of unresolved cases.

Using genetic adaptation to high altitude to discover mechanisms regulating acute responses to ischemia

Principal Advisor: Associate Professor Nathan Palpant (n.palpant@uq.edu.au)

Associate Advisors: Professor Glenn King (glenn.king@imb.uq.edu.au), Dr Sonia Shah (sonia.shah@imb.uq.edu.au) and Dr Toby Passioura (University of Sydey)

Human populations living in high-altitude hypoxic environments have shown generational gene adaptations compared to lowland cohorts. These extreme stresses result in adaptive changes in the genome to maintain cell viability and function. We hypothesise that genes adapted to high altitude provide a unique approach for discovering novel mechanisms to protect organs from acute ischemic stresses like heart attacks. My laboratory is studying the genetics of lowland versus highland populations in China and Central America and using human pluripotent stem cells (hiPSCs) to study genes selected for high-altitude survival. Preliminary single-cell RNA-seq analysis of differentiated European vs. Han Chinese iPSCs revealed a unique gene expression signature for hypoxia pathways shared by the Han Chinese iPSCs with high altitude-associated haplotypes. We have also identified the gene encoding TMEM206, an acid-sensing ion channel, as a candidate “high-altitude gene”. Genetic knockout of TMEM206 reduces cardiomyocyte sensitivity to ischemia. These data and cell tools are a rich resource for discovering genes under adaptive pressure that could in turn reveal mechanisms and drug targets for protecting the heart against acute injury. This project will use iPSCs selected by known high-altitude haplotypes and compared using in vitro ischemia assays to measure cardiomyocyte cell death. We will analyse haplotype differences in differentiated cardiomyocytes by RNA-seq to identify gene expression programs associated with high altitude-adapted genotypes. We will then use the Broad Institute Connectivity MAP, which links drug perturbations to gene expression changes, to identify novel drugs that induce a “high altitude” gene expression profile in cardiomyocytes. Candidate drugs will be tested in wildtype cells (lacking the high-altitude haplotypes) to assess efficacy in reducing cell death during acute ischemic stress. Using our CRISPR gene methods, we will also knockout candidate “high-altitude genes” identified from statistical genetic studies and assay them using in vitro acidosis/ischemia models. For genes such as TMEM206 that show a role in mediating cardiomyocyte cell death, we will work with associate supervisors Glenn King (UQ) and Toby Passioura (U Sydney) in using the RaPID screen to discover cyclic peptides that inhibit stress-sensitive ion channels.

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