PhD Projects

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.

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.

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.

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

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

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.

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 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.

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.

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.

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.

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.

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.

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 prostate cancer models.

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.

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.

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.

Principal Advisor: Dr Conan Wang (IMB)

Must commence by Research Quarter 3, 2025.

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.

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.

1. Next-generation anti-cancer drugs
2. Antimicrobial agents to fight infection
3. Bio-friendly drugs to control agricultural pests
4. 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.

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.

Principal Advisor: Dr Zeinab Khalil (IMB)

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

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. 

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. 

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. 

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 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.

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.

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.

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.

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.

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.
 

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. 

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.

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.

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)

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.

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

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.

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.

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.

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.

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.  

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.

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.

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.

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.

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).

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. 

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.

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.

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

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.

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.