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 'Standard PhD Projects' and 'Earmarked PhD Projects'. Please select a Centre to explore all available PhD projects in that category. Sign up to alerts to be notified of any new PhD projects and for any queries, please contact the HDR Liaison Officer, hdr.imb@enquire.uq.edu.au.
Standard PhD Projects
All standard PhD Projects qualify for a UQ Graduate School Scholarship. Those marked with an asterisk (*) qualify for an additional scholarship, the IMB Global Challenges Scholarship, which is a top-up to the 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. The IMB Global Challenges Scholarship is managed privately by IMB. To be considered, please register your interest via this form. Sign up to alerts to be notified of application dates (once released) as well as other PhD opportunities.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*Mapping chemical diversity in Australian marine microbes
Principal Advisor: Dr Zeinab Khalil (IMB)
Associate Advisor: Prof Rob Capon (IMB); Prof Ian Henderson (IMB)
Australia’s marine territory is rich with vast microbial diversity that remains unexplored. These microbes harbour the next generation of environmentally responsible resources and products (new molecules). Knowledge of microbial chemical diversity can significantly advance our understanding to enhance the discovery of small molecules that can be used as bioactive products, such as anti-infective, antiparasitics, and crop protection fungicides.
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.
The successful candidate will join a Marine bioproducts cooperative research centre (MB CRC) funded project and multi-disciplinary team 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 an interest in learning multidisciplinary biosciences.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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)
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.
*Qualifies for the Global Challenges Scholarship.
*Targeting the oxytocin receptor for breast tumour reduction
Principal Advisor: A/Prof Markus Muttenthaler (IMB)
Associate Advisor: A/Prof Loic Yengo (IMB)
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 the development of therapeutic leads 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 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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*The physiological role and therapeutic potential of gut peptides modulating appetite
Principal Advisor: A/Prof Markus Muttenthaler (IMB)
Associate Advisor: Dr Sebastian Furness (UQ School of Biomedical Sciences)
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 most kinds of 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 socioeconomic 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.
*Qualifies for the Global Challenges Scholarship.
*The therapeutic potential of the trefoil factor family in chronic gastrointestinal disorders
Principal Advisor: A/Prof Markus Muttenthaler (IMB)
Associate Advisor: Prof Alpha Yap (IMB)
Inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS) affect 10–15% of the Western 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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*Vaccine Engineering
Principal Advisor: Prof Denise Doolan (IMB)
Associate Advisor: Prof Tim Mercer (AIBN); Prof Mark Walker (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.
Subject areas: Immunology, Vaccinology, Molecular immunology, Malaria, Vaccine engineering, Vaccine design
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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*PET Imaging of Bacterial Infections
Principal Advisor: A/Prof Mark Blaskovich (IMB)
Associate Advisor: Prof Kristofer Thurecht (UQ Centre for Advanced Imaging); Dr Anthony Verdosa (IMB)
Infections caused by drug resistant bacteria pose a significant threat to global human health, with predicted annual mortality of 10 million by 2050. Most research is focused on developing better therapies, but improving diagnosis could quickly have substantial impact by reducing unnecessary antibiotic use and enhancing therapeutic efficacy. There is no current clinical technology capable of specifically identifying bacterial infections by imaging the site of a bacterial infection. Suspected chronic infections, such as endocarditis and prosthetic joint infections, are particularly difficult to accurately diagnose without invasive techniques. A whole-body imaging diagnostic that could simultaneously determine whether an infection was present and rapidly pinpoint the site of the infection, then monitor the efficacy of subsequent treatment, would directly inform targeted treatment, leading to substantial health and economic benefits. This project will extend our current research on fluorescent tracers that bind to the surface of bacteria with high specificity and selectivity. We will replace the fluorophore component of these tracers with radioisotope chelating ligands, creating new constructs suitable for positron emission tomography (PET) whole body imaging. These tracers will be tested both in vitro and in mice to demonstrate specific PET imaging of bacterial infections.
*Qualifies for the Global Challenges Scholarship.
*Targeting bacterial cell envelope coordination for antibiotic drug discovery
Principal Advisor: Prof Waldemar Vollmer (IMB)
Associate Advisor: Prof Brett Collins (IMB); Mr Alun Jones (IMB)
The project is integrated into the BREAKThrough EU ITN project (see information below) and offers unique opportunities for research collaborations and training for the PhD student. The student will undertake secondments (each 2 months) at Newcastle University (UK) and Vrije Universiteit Amsterdam (The Netherlands).
Gram-negative bacteria have a multi-layered cell envelope with an outer membrane that is tightly connected to the underlying peptidoglycan cell wall layer. The outer membrane protects the cell from many toxic molecules and lysins, and the peptidoglycan layer confers osmotic stability and its biosynthesis is the target of some of our best antibiotics. Growing and dividing bacteria transport all outer membrane components (lipopolysaccharide, outer membrane proteins, phospholipids) through the pores of the net-like peptidoglycan and insert them into the outer membrane, using dedicated and sophisticated multi-protein machineries. One of these, the BAM complex, folds outer membrane beta-barrel proteins (OMPs, porins) into the outer membrane. How outer membrane biogenesis is coordinated with peptidoglycan growth is largely unknown. The PhD project will follow our recent work showing that peptidoglycan maturation controls the activity of the BAM complex (Mamou et al., Nature 2022). The PhD student will use a range of techniques in molecular biology, microscopy and protein biochemistry to decipher how BAM proteins interact with peptidoglycan and other cell envelope factors, and how these interactions affect BAM function in the test tube and cell. The project is expected to discover molecular mechanisms that can be targeted by new molecules that disrupt cell envelope coordination in bacteria.
Reference: Mamou G, Corona F, Cohen-Khait R, Housden NG, Yeung V, Sun D, Sridhar P, Pazos M, Knowles TJ, Kleanthous C, Vollmer W. 2022. Peptidoglycan maturation controls outer membrane protein assembly. Nature 606, 953-959. (https://pubmed.ncbi.nlm.nih.gov/35705811/)
BREAKThrough (European International Training Network)
Antimicrobial resistance is a global health emergency. The growing number of drug-resistant pathogens is making common infections more and more difficult to treat. Gram-negative bacteria, a major cause of infections in recent years, are resistant to almost all antibiotics, leaving no option for treatment at all. BREAKthrough is a Doctoral Network which aims to make these bacteria susceptible to today’s standard-of-care antibiotics. Since the bacteria’s outer membrane prevents antibiotics from entering the cell, the project will develop new compounds that ultimately damage the outer membrane and allow antibiotics to break through the bacterial cell wall. BREAKthrough is funded under Horizon Europe’s Marie Skłodowska-Curie Actions (MSCA) programme.
Project Website: https://breakthrough-project.eu/
Candidate profile
• Keen interest in molecular biosciences.
• Excellent interpersonal and team-working skills.
• Motivated to work in a research team and undertake collaborative research with BREAKthrough partners, willingness to undertake medium term (2 months) research secondments in Europe.
• Knowledge and practical experience in bacterial growth, microscopy, genetic methods, protein biochemistry.
• Master degree in Microbiology, Biochemistry, or a related discipline
*Qualifies for the Global Challenges Scholarship.
*Targeting the membrane steps in bacterial cell wall synthesis for antibiotic drug discovery
Principal Advisor: Prof Waldemar Vollmer (IMB)
Associate Advisor: Mr Alun Jones (IMB); Prof Rob Capon (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. We study the key essential steps of cell wall synthesis at the cell membrane, 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 new assays to measure the activities of membrane-bound cell wall enzymes. The PGR student will then use the new assays in proof-of-principle studies to screen for new inhibitors. 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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*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.
*Qualifies for the Global Challenges Scholarship.
*Understanding the genetics of antibody dependent enhancement of disease
Principal Advisor: Dr Sonia Shah (IMB)
Associate Advisors: Dr Larisa Labzin (IMB), Dr Tim Wells (Frazer Institute); Prof Ian Henderson (IMB)
Antibodies are essential components of the adaptive immune system, which function in the clearance of infection and protection against reinfection. The role antibodies play in binding specifically to microbial antigens, neutralising their function, stimulating complement-dependent killing, and opsonization of the pathogen to promote clearance by macrophages and other immune cells, are well established. However, there is a growing appreciation that antibody can also drive disease pathology. Recent studies have demonstrated antibody-dependent enhancement (ADE) of bacterial infections resulting in more severe clinical outcomes. By stratifying patients with and without ADE, our group developed a treatment to treat multidrug resistant infections, successfully resolving life-threatening infections. While the molecular mechanisms of ADE of infection is beginning to be elucidated, why certain patients produce these deleterious antibodies remains unknown. Investigation of multiple cohorts of patients with differing infections reveal a consistent percentage of patients displaying ADE of disease suggesting a genetic basis for this phenomenon. Working with clinicians, molecular biologists and geneticists, this project seeks to determine if there is a genetic signature for ADE of bacterial infection.
*Qualifies for the Global Challenges Scholarship.
Earmarked PhD Projects
Earmarked PhD Projects are projects that are aligned to recently awarded research grants. They are accompanied by a UQ Earmarked Scholarship which is funded by the Australian Government and offered to support candidates with their living costs and tuition fees. Applications are now open and Domestic as well as International (onshore and offshore) candidates may apply. Please see project description to view the project's individual application deadline.
When you are ready to apply, please contact the Principal Advisor via email ensuring the project title is in the subject line and your latest CV is attached. Once you have confirmation that they will endorse you for your chosen project, you may officially apply via the UQ Application Portal making sure you select 'Earmarked Scholarship'. Sign up to alerts to be notified of any new Earmarked PhD projects as well as other PhD opportunities.
Characterising a specific regulator of venous vessel integrity
Principal Advisor: Dr Anne Lagendijk (IMB)
Associate Advisor: Dr Emma Gordon (IMB)
Must commence by Research Quarter 1, 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.
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.
*Qualifies for an Earmarked Scholarship.
Early warning mechanisms for epithelial tissue self-protection
Principal Advisor: Prof Alpha Yap (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.
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.
*Qualifies for an Earmarked Scholarship.
Host-Microbe Interactions and the circadian clock in Liver Disease
Principal Advisor: Dr Benjamin Weger (IMB)
Must commence by Research Quarter 1, 2026
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.
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.
*Qualifies for an Earmarked Scholarship.
Migration dependent signalling in immune cells
Principal Advisor: Prof Jennifer Stow (IMB)
Must commence by Research Quarter 1, 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.
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.
*Qualifies for an Earmarked Scholarship.
Peptide absorption in the gastrointestinal tract and development of peptide drugs
Principal Advisor: Prof Jennifer Stow (IMB)
Must commence by Research Quarter 1, 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.
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.
*Qualifies for an Earmarked Scholarship.
Development of venom-derived blood-brain barrier shuttles
Principal Advisor: A/Prof Markus Muttenthaler (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.
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.
*Qualifies for an Earmarked Scholarship.
Engineering high-efficiency light-driven synthetic biology
Principal Advisor: Prof Ben Hankerman (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.
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.
*Qualifies for an Earmarked Scholarship.
Investigating the role and therapeutic potential of the oxytocin receptor in prostate cancer
Principal Advisor: A/Prof Markus Muttenthaler (IMB)
Associate Advisor: A/Prof Jyotsna Batra (QUT)
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 prostatecancer 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.
Modulating protein-protein interactions in disease
Principal Advisor: Prof David Fairlie (IMB)
Must commence by Research Quarter 1, 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.
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.
*Qualifies for an Earmarked Scholarship.
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
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.
- 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.
*Qualifies for an Earmarked Scholarship.
Photocontrollable probes to study neuropeptide-mediated memory formation
Principal Advisor: A/Prof Markus Muttenthaler (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.
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.
*Qualifies for an Earmarked Scholarship.
Targeting strategies for drug design
Principal Advisor: Prof David Fairlie (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.
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.
*Qualifies for an Earmarked Scholarship.
Tuning the activating stimulus of voltage-gated sodium channels
Principal Advisor: Dr Angelo Keramidas (IMB)
Must commence by Research Quarter 1, 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.
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.
*Qualifies for an Earmarked Scholarship.
1. Identifying new targets for treatment of antimicrobial resistant infections
Principal Advisor: Prof Ian Henderson (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.
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.
*Qualifies for an Earmarked Scholarship.
Sometimes Correlation does Equal Causation: Developing Statistical Methods to Determine Causality Using Genetic Data
Principal Advisor: Prof David Evans (IMB)
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).
*Qualifies for an Earmarked Scholarship.
Testing effect of environmental exposures on subsequent human generations
Principal Advisor: Dr Gunn-Helen Moen (IMB)
Must commence by Research Quarter 1, 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.
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
*Qualifies for an Earmarked Scholarship.
Using genetics to understand the relationship between early life growth and future risk of cardio-metabolic disease
Principal Advisor: Dr Nicole Warrington (IMB)
Must commence by Research Quarter 1, 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.
Rapid weight growth during infancy and changes in body mass index (BMI) throughout childhood are associated with increased risk of cardio-metabolic diseases in later life, suggesting that early life interventions could be beneficial. Although implementing lifestyle interventions prior to the onset of disease is likely to be the most cost-effective strategy for reducing the impact of these conditions on society, the optimal time to intervene remains unclear. Mendelian randomization, a method that is analogous to a randomized controlled trial but involves individuals’ genotypes rather than treatments, can assess the causal effect of early life weight growth on cardio-metabolic disease risk, therefore identifying potential times for intervention. This project will use statistical genetics methods to investigate whether there is a time period in early life where rapid weight growth causes increased risk of cardio-metabolic disease in later life.
The successful candidate will gain experience across a wide range of advanced statistical genetics methodologies including Mendelian randomization, 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. Depending on the candidate’s level of experience, they will help develop and/or apply statistical genetics approaches to longitudinal data from the UK Biobank and the Early Growth Genetics Consortium.
*Qualifies for an Earmarked Scholarship.
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