Honours Projects - Institute for Molecular Bioscience

See below for a list of Honours project opportunities. To apply, please send an expression of interest to the relevant Supervisor(s) ensuring you include a copy of your CV and academic transcript. Apply anytime!

Research Groups Honours Homepage

Advancing 3D imaging and visualisation of cell surfaces

Biochemical and structural studies of membrane trafficking protein complexes involved in neurodegeneration

Blocking nutrient uptake to limit cancer cell survival

Cancer metastasis and stem-like reprogramming via mechanical signatures

Characterising the impact of neurological injury on coronary sinus biomarker profile in an ovine model of circulatory determination of death

Supervisors: Dr Jacky Suen (j.suen1@uq.edu.au); Ms Molly McInerney (m.mcinerney@imb.uq.edu.au)

To characterise the coronary sinus (CS) biomarker profile and catecholamine surge after neurological injury in an ovine model of circulatory determination of death (DCD). The molecular characterisation of the CS profile will improve our understanding of the physiological changes directly inside the heart during DCD for the purpose of heart transplantation.

Characterising the impact of neurological injury on cytokine profile in an ovine model of circulatory determination of death

Supervisors: Dr Jacky Suen (j.suen1@uq.edu.au); Ms Molly McInerney (m.mcinerney@imb.uq.edu.au)

To determine if neurological injury impacts circulating inflammatory cytokines and cardiac injury markers within an ovine model of circulatory determination of death (DCD). The identification of this biomarker profile will improve our understanding of the physiological changes during DCD and their implications for heart transplantation.

Characterising the impact of neurological injury on hearts reconditioned with hypothermic oxygenated machine perfusion (HOPE) in a model of circulatory determination of death (DCD) for heart transplantation

Circadian regulation of protein glycosylation

Controlling cell fate through transcription factor-based reprogramming

Deciphering the DNA-protein interactions that reset the ageing clock during reprogramming

Designing mini-protein chaperones for dementia treatment.

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

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

Determining the impact of neurological injury on cardiac contractile function in an ovine model of circulatory determination of death

Do cells experience nuclear damage in the absence of microtubules?

Supervisors: Dr Samantha Stehbens (s.stehbens@uq.edu.au), Dr Robert Ju (r.ju@uq.edu.au)

Cells can generate and transmit mechanical forces. Physical compression of cells (such as a cell invading through a dense tissue) can result in damage to the nucleus. This can drive adaptations in nuclear biology. This project will examine how the nucleus responds to force in the absence of the microtubule cytoskeleton.

Endocytosis of Endothelial Nitric Oxide Synthase in Cardiovascular Disease

Engineering cell identity: Using human pluripotent stem cells to program cells with customised functions not seen in the natural world

Supervisor: Dr Nathan Palpant (n.palpant@uq.edu.au)

This project seeks to explore the frontier of cell engineering by utilizing pluripotent stem cells as a model system. These stem cells, known for their ability to differentiate into any cell type, will be manipulated to remove the epigenetic barriers that conventionally restrict cell identity. By transcending these intrinsic limitations, the study aims to engineer cells with functions and characteristics not observed in the natural world. The potential impact of this work extends not only to fundamental discovery science, where it may open new avenues in understanding cellular differentiation and control, but also to translational applications. Innovations in synthetic biology could emerge from this research, impacting areas such as tissue engineering, regenerative medicine, and the development of novel therapeutic strategies.

Examining a novel regulator of blood vessel integrity

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

A healthy vasculature is central to a functioning cardiovascular system. One aspect imperative to a homeostatic vascular system is stability of the endothelial cell (EC) monolayer, which forms the inner wall of all vessels. We have recently identified striking vascular defects in zebrafish lacking a selected soluble peptide receptor. CRISPR/Cas9 targeting of the gene encoding this receptor induced severe bleedings in the zebrafish brain by three days post fertilisation (dpf). This data suggests that this receptor is essential to strengthen the vasculature and prevent bleedings. This project aims to further characterise this unique phenotype and uncover the underlying mechanisms.

Fighting infection: Enhancing phagocytosis and pathogen killing

How (ab)normal mechanics controls the health (or not) of the eye epithelium

How cytokines increase sensitivity to inflammation triggered by apoptosis in epithelia

How does the tumour mechano-environment facilitate melanoma brain metastasis?

How immune cells eat and digest pathogens; phagocytosis

Immune navigation: changing signals to control inflammation in disease

Investigating a newly identified mechanism of innate immune defence using tissue culture and zebrafish models

Investigating a novel pathway that controls venous blood vessel integrity

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

A healthy vasculature is central to a functioning cardiovascular system. One aspect imperative to a homeostatic vascular system is the integrity of junctions between adjacent endothelial cells (ECs). It is appreciated that arteries and veins display different adhesive properties at EC junctions, underpinning their distinct functions. However, the molecular mechanisms controlling this heterogeneous adhesion and junction integrity across divergent vessel types are not well understood.

Preliminary data in our lab has uncovered a novel factor that specifically controls venous EC adhesion. We have shown this specific role in both loss-of-function zebrafish and 3D bioengineered human vessels, displaying disrupted venous endothelial junctions and venous vessel dysmorphia. Notably, arteries are unaffected. Such vessel-restricted phenotypes are rare, and this project aims to characterise the cellular mechanisms that determine this specificity. We are seeking an enthusiastic and driven Honours student to assist in the phenotyping of novel zebrafish CRISPR knockout lines that have been generated as part of this project. You will gain skills in zebrafish handling, molecular cloning, CRISPR/Cas9 gene editing and high-resolution live imaging of functioning blood vessels. Specific project aims include:

1. Phenotypic rescue experiments by re-expressing genes in zebrafish knockout models

2. Determine the functional consequences of compromised ECs (i.e. vessel hyperpermeability or breakdown) using dextran injections

3. Assist in phenotyping of novel CRISPR/Cas9 zebrafish mutant lines to help delineate the key players in this novel venous specific pathway

Investigating the role of the vasculature in COVID-19

Leveraging single cell multiome data to identity drivers of organ ageing (dry lab/computational project)

Live imaging of cell lineage differentiation in a novel transgenic quail model

Mitochondrial transplantation for cardiac transplantation

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

Donor hearts experienced secondary injury during transplantation which increases the risk of primary graft dysfunction and patient mortality. One approach to improve donor heart condition is through mitochondrial transplantation. Student will work with our collaborator at Harvard Medical School to optimise the extraction, preparation and application of mitochondria onto donor heart in a preclinical model.

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

Oxygenator-induced haemolysis in advanced life support

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

Student will conduct benchtop experiments to examine the role of oxygenator in device-related haemolysis. Patients with cardio-respiratory failure are often supported by advanced life support, and face complications such as bleeding. The student will build on our previous data showing that oxygenator is a cause of haemolysis that has not been reported before.

Regulation of liver protein secretion and its regulation by circadian and feeding rhythms

Role of macrophage metabolism in driving inflammation

Role of macrophage metabolism in host defence against bacterial infections

Screening for metastasis inhibitory markers in cancer

Specific role of the circadian clocks in the different liver cell types and how they interact

Studies of membrane trafficking protein complexes involved in neurodegenerative disease using X-ray crystallography and cryoelectron microscopy

Targeting Nanoparticles to Fight Cancer

Targeting stress and protein quality control pathways in skeletal muscle disease

Supervisors: Amy Hanna (a.hanna@imb.uq.edu.au); A/Prof Nathan Palpant (n.palpant@uq.edu.au)

Skeletal muscle is an active, highly dynamic tissue that is constantly building new proteins to perform integral muscle activities like contraction, temperature regulation and energy expenditure. In healthy muscle, misfolded proteins are removed before they can affect cellular health but in some muscle diseases these misfolded proteins remain in the cell and aggregate, causing activation of stress pathways. How these misfolded proteins affect the ability of muscle to function is poorly understood. This project will examine the factors that regulate protein folding in skeletal muscle and determine how the accumulation of misfolded proteins affects muscle contraction and muscle size. We will also determine if these stress pathways can be targeted to treat congenital myopathy by testing novel pharmacological agents in models of human muscle disease.

The role of BAR proteins in directing collective cell migration during blood vessel development

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

The growth of new blood vessels is governed by polarisation and directional collective migration of the endothelial cells that make up these vessels. BAR proteins are a protein family characterised by the BAR domain, a membrane curvature sensing module that senses and actively induces membrane curvatures. As part of an international collaboration, we have identified BAR proteins that specifically regulate polarisation and collective cell migration in confluent endothelial cell cultures subjected to scratch wounds as well as in growing blood vessels in zebrafish. We have now generated stable zebrafish knockout lines for these BAR proteins. This project will utilise these novel zebrafish lines to identify how these BAR proteins control collective cell migration by high resolution live imaging of developing vasculature. Overall this project provides the unique opportunity to be part of an international team and perform state-of-the art live imaging to reveal novel cellular behaviours that are relevant to blood vessel function.

The role of caveolae in cancer

Understanding acid sensitivity of the heart: identifying genes and drugs that block the injury response of the heart during ischemic stress

Supervisor: Dr Nathan Palpant (n.palpant@uq.edu.au)

This project aims to explore heart injury mechanisms that occur under low-oxygen conditions. Drawing insights from studies on high altitude adaptation, the project aims to uncover genetic factors that may confer tolerance to hypoxic environments. These discoveries are anticipated to facilitate the identification of novel genetic targets that can be employed in the treatment of patients suffering from heart attacks. Utilizing human pluripotent stem cells, ischemia will be modeled in vitro to test new genes or pharmacological agents that prevent cell death under acute stress conditions. Given that heart attacks represent the leading cause of death globally, the findings of this project will offer innovative strategies to alleviate the substantial burden associated with cardiac diseases.

Understanding microtubule-dependent cell invasion to enhance innate immune responses

Unlocking Vascular Control: Investigation of a Novel Gene Regulating Blood Pressure for Therapeutic Development

Supervisor: Dr Nathan Palpant (n.palpant@uq.edu.au)

This project aims to study a newly discovered gene that plays a crucial role in controlling vascular development and regulating blood pressure. We aim to understand the mechanisms and functions of this gene to open new avenues for the development of novel therapeutics specifically tailored for blood pressure management. Utilizing an integrative approach that combines animal models, stem cell models, and genetics, the study will dissect the pathways and functions of this gene. The project will contribute to the expanding body of knowledge surrounding genetic control of vascular function, thus enhancing our comprehension of blood pressure regulation at a molecular level. The outcomes may lead to the creation of new drugs, providing approaches to treat hypertension and other blood pressure-related diseases.

Water bears (tardigrades) as a system to study stress resistance

Zinc toxicity as an antimicrobial weapon of macrophages

AEP-mediated biosynthesis of orally active cyclotide-based antagonists for bradykinin B1 receptor

Benchmarking deep learning methods for designing active peptides

Boosting accumulation of cyclisation-stabilised peptide-based pharmaceuticals in plant seeds

C-fos: a measure of pain in chemotherapy induced neuropathy

Characterization of blood-brain barrier nutrient transporters

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

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

Chemical strategies to deliver peptide drugs into cells

Chemical synthesis and structure-activity-relationship studies of the trefoil factor family

Computational design of targeted cancer therapeutics guided by machine learning

Defining cylclotide membrane interactions using nanodisc

Dehydrating microalgal to extend their shelf-life for medical and agricultural use.

Design and characterisation of a new generation of anti-obesity peptides

Design and characterisation of a next-generation antimicrobial peptide

Designing experimental drugs using computers and structure-based drug design

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Huy Hoang (h.hoang@imb.uq.edu.au)

Computational approaches can be powerful aids for drug discovery as they combine and amplify the power of three dimensional structures of both small molecule drug leads and protein targets with molecular insights to disease development. This project will use computer-based methods to design, discover and optimise new candidate drug leads.

Designing protein drugs for the treatment of cancer and inflammatory diseases

Supervisor: Dr Conan Wang (c.wang@imb.uq.edu.au)

Cytokines are signalling proteins that play essential roles in immune responses and have garnered clinical interest in the context of cancer, autoimmunity, and infectious disease. This project aims to overcome their limitations of poor stability, activity, and specificity to develop new therapeutics. Candidates will learn new skills in drug design and characterisation using tools in molecular biology, biochemistry, and structural biology.

Determining three-dimensional structures of protein modulators using NMR spectroscopy

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Huy Hoang (h.hoang@imb.uq.edu.au)

Three-dimensional structures of compounds in solution determine their activities on biological targets (e.g. proteins, DNA, RNA). NMR spectroscopy is the most powerful and versatile method to elucidate solution structures, dynamics and interactions of chemical compounds alone and with their targets. This project will give opportunities to solve three dimensional structures of bioactive fragments of proteins and small molecule modulators of proteins.

Developing microalgae soil additives that improve soil health

Developing new drugs for inflammatory bowel disease

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Eunice Poon (k.poon@uq.edu.au)

Inflammatory bowel disease (IBD) is a collection of complex chronic inflammatory conditions of the gastrointestinal tract. It is currently treated with immunosuppressives that are associated with significant, often severe, side effects. This project will evaluate the effectiveness of new therapeutic compounds with different mechanisms of action using a mouse model of colitis and various molecular biology techniques.

Developing new mass spectrometric methods for the rapid identification and assignment of absolute configuration to chiral amino compounds

Development of gut-stable peptide hormones

Discovery of novel ion channel modulators from cone snail venoms

Discovery of novel sodium channel modulators from venoms

Efficient design of drugs using new nanoscale technologies

Supervisor: Dr Conan Wang (c.wang@imb.uq.edu.au)

Powerful technologies have emerged to perform millions of experiments quickly in tiny nanolitre droplets, and have attracted wide interest from major pharmaceutical companies because of the potential to accelerate drug discovery. Honours project opportunities are available to investigate these next-generation tools for drug design and learn new skills in one or more areas of nanotechnology and molecular biology.

Efficient extraction of recombinant proteins from algae

Fine-tuning the application of peptide-based antimalarial drugs through understanding their mechanism of action

Supervisor: Dr Nicole Lawrence (n.lawrence@uq.edu.au)

Malaria is a disease caused by Plasmodium parasites. The disease kills half a million people every year and the parasites rapidly evolve resistance to new drugs. Developing new drugs with different ways of killing the parasites is important for staying ahead of the disease progression. We have developed peptide-based drugs that target red blood cells infected with malaria parasites. The peptides are safe and selective and are also less likely to result in the parasites developing drug resistance compared to existing small molecule drugs.
We are seeking a motivated Honours student to join our discovery team and contribute valuable knowledge required for developing lead peptides into new treatments for malaria.
The overall aim of the project is to undertake genetic studies to understand how lead peptides affect malaria parasites at transcription and protein expression levels

GABA-A receptor variants in epilepsy

Genetic exploration of Petunia as a novel platform for producing cyclisation-stabilised peptide-based pharmaceuticals

Glycine receptor variants in autism spectrum disorder

Improving photosynthetic oxygen for food and therapeutics

Leveraging Hudson Robotic Technology for Soil Microbe Cultivation and Crude Extract Library Generation

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

In our quest to unlock the hidden potential of soil microbes, we are embarking on an innovative project utilizing cutting-edge Hudson Robotic technology. The initiative focuses on cultivating diverse microbes sourced from soil samples, transforming them into a comprehensive crude extract library.

The Hudson Robotic system brings efficiency and precision to the cultivation process, enabling high-throughput growth of microbes from various soil sources. This automated approach streamlines the generation of a robust crude extract library, capturing the chemical diversity inherent in these microorganisms.

The project's objectives include harnessing the vast microbial diversity present in soil and creating a valuable resource for further exploration. By employing state-of-the-art technology, we aim to expedite the discovery of novel compounds with potential applications in medicine, agriculture, and beyond.

Join us in the frontier of microbial research, where Hudson Robotic technology serves as a catalyst for cultivating and cataloging diverse soil microbes, paving the way for a wealth of possibilities in drug discovery and biotechnology.

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

Mechanisms of cell uptake by macrocyclic drug

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Liping Liu (liping.liu@uq.edu.au)

Protein-protein interactions are responsible for most biological processes and so proteins and their peptide fragments hold immense promise for treating diseases. However, to be used as medicines they must first penetrate cellular membranes which is a key problem. Endocytosis is the principal mechanism of cellular uptake but peptides often get trapped in endosomes and mechanisms of escape into the cytoplasm are not well understood. This project will study diverse peptide structures for cell uptake and findings may help in designing new drugs with enhanced cellular delivery.

Method development for chemical synthesis of proteins

Modulating Potassium Channels for Immune Cell Activation

Supervisor: Professor Irina Vetter (i.vetter@imb.uq.edu.au); Dr Hana Starobova (h.starobova@imb.uq.edu.au)

Macrophages are innate immune cells that are crucial for initiating immune response. Macrophage activation is implicated in driving many painful pathological stages, including neuropathy and inflammatory pain. Potassium channels, such as Kv1.3, regulate cell potassium homeostasis, and any dysregulation in intracellular potassium can lead to macrophage activation and resultant cytokine and chemokine release, driving pathogenesis of pain. This project will investigate the effects of specific potassium channel-targeting toxins on macrophage activation using electrophysiology techniques, live cell fluorescent microscopy, and in vivo rodent behavioural studies.

Neuro-immune interactions involved in painful neuropathies

Neuropeptides and long-term memory formation

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

Memory is probably the single most important brain process that defines our personality and gives us the sense of individuality. Emotional events often cause the generation of strong memories that exist for many years, yet the underlying mechanisms are still poorly understood. Neuropeptides are key players in regulating emotions and have been associated with long-term memory formation. This project is focused on the development of advanced molecular probes to understand how neuropeptides can mediate long-term memory formation.

Neuropeptides and their role in memory formation

New antiparasitic to protect Australian livestock

NLRP3 inflammasome activation by chemotherapies and the therapeutic application

NMDA receptor variants in neurological disorders

NMR structures and computational studies to design bioavailable peptides

Oxytocin and Vasopressin Research

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

The oxytocin and vasopressin signalling system regulates fundamental physiological processes such as reproduction, water balance, cardiovascular responses and complex social behaviour. It is also a high-profile target for autism, schizophrenia, stress, depression, anxiety, cancer and pain. Our group is particularly interested in creating a complete molecular toolbox to study this signalling system as well as in discovering novel therapeutic leads for autism, pain, gastrointestinal disorders and breast cancer. This project entails structure-activity-relationship studies and medicinal chemistry approaches to develop novel probes and drug candidates for the oxytocin and vasopressin system.

Pesticides targeting invertebrate synaptic receptors

Pharmacology of Stinging Nettle venom

Protein Engineering using a new class of ligase enzymes

Reassessing the classification of conotoxin genes into superfamilies

Reengineering of wasp venom peptides for antimicrobial applications

Regulating mucin protection against microbes in our gut

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Eunice Poon (k.poon@uq.edu.au)

The intestine is lined with a layer of mucus which acts as a protective barrier against microbial invasion. Mucins are a major component of this layer and are secreted mainly by goblet cells in the epithelium. We have identified a protein that, when activated, depletes mucins from goblet cells. The exact mechanism for this effect is unknown. This project aims to further understand this process by using in vivo and ex vivo techniques and to regulate the process using novel drug leads.

Role of adhesion molecules in chemotherapy induced side effects

Single-channel analysis of voltage-gated sodium channels

Soils for Science - Searching the soil microbes for new antibiotics

Soils for Science - Searching the soil microbes for new antifungals

Stapled peptides as anticancer drugs

Structure-activity relationships of cyclic dynorphin A analogues targeting kappa opioid receptors

Synthesis and oxidative folding pathway of disulfide-rich cyclic peptides

Synthesis of bacterial metabolite analogues as anti-inflammatory drugs

Synthesis of DNA-binding peptides for anti-cancer therapy

Synthesis of fluorescent probes for visualising an inflammatory protein in cells

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Jeff Mak (j.mak@imb.uq.edu.au)

Class IIa histone deacetylases (HDACs) are enzymes involved in regulating inflammation in humans. Unlike other HDACs, they do not localise within the nucleus, but shuttle between the nucleus and the cytosol. The project aims to synthesise fluorescent ligands for studying and visualising these processes.

Synthesis of long-acting antidiabetic agents

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Tim Hill (t.hill@imb.uq.edu.au)

Derivatives of the hormone glucagon-like peptide have been used to treat diabetes and more recently obesity. We have previously developed compounds like this hormone that have profoundly different effects on cells, but with poor drug-like properties such as plasma instability. This project aims to synthesise compounds that can similarly alter cell signalling profiles but have enhanced drug-like properties that make them potential drug candidates for testing in mose models of diabetes and obesity.

Synthesis of modified bacterial metabolites as anti-inflammatory drugs

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Jeff Mak (j.mak@imb.uq.edu.au)

Mucosal associated invariant T cells (MAIT cells) are antibacterial immune cells that are activated by small molecule bacterial metabolites. However, their excessive activation can contribute to inflammatory diseases such as colitis. This project aims to modify bacterial metabolites to produce new MAIT cell inhibitors as potential leads to a new class of anti-inflammatory drugs.

Synthesis of neuropeptide tracers with increased sensitivity for cancer imaging

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

Fluorescently labelled peptides have emerged as promising tools for the detection and visualisation of cancer, the specificity of peptide ligands combined with non-invasive optical imaging presents many favourable characteristics over radiopharmaceutical imaging techniques. Several neuropeptide receptors have been identified as significantly upregulated in some cancers and due to the high specificity of their endogenous peptide hormones present an opportunity for the development of fluorescent neuropeptide tracers for the detection and visualisation of these cancers. This project will involve chemical synthesis, purification and characterisation, cell biology, and confocal microscopy.

Synthesis of novel 8-membered heterocycles towards new cancer drugs

Targeted delivery of anticancer drugs

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Tim Hill (t.hill@imb.uq.edu.au)

Most approved cancer therapeutics are designed to be cytotoxic and interfere with cellular proliferation. Consequently, they are usually also toxic to normal cells and cause side effects, presenting a major challenge to achieve both therapeutic efficacy and safety. One way to try and over come this problem is to create targeted drug conjugates which contain a protein or peptide which can selectively interact with cancer cells whilst delivering a known cytotoxic drug to the target. This project aims to create peptide-drug conjugates which can be targeted to cancer cells which overexpress specific receptors.

Targeting gut biofilms in patients with gastrointestinal disorders

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

Gastrointestinal disorders affect 10–15% of the Western population, reduce the quality of life and result in substantial socioeconomic costs. Recently, we have observed bacterial biofilms in the gastrointestinal tract of IBD and IBS patients, but their disease relevance, function and composition are unknown. This project aims to (i) use various analytical techniques to profile these gut biofilms and (ii) to develop biofilm-specific modulators to explore novel therapeutic strategies.

Targeting the oxytocin receptor in breast or prostate cancer

Trefoil factor peptides and their role in gastrointestinal disorders

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

The gastrointestinal epithelium is a major physical barrier that protects us from diverse and potentially immunogenic or toxic content. A damaged epithelium increases permeability to such content, thus leading to inflammation, uncontrolled immune response, and diseases, such as irritable bowel syndrome and inflammatory bowel diseases that affect 10-15% of the population. Our group is involved in the identification and validation of novel drug targets and therapeutic strategies that can protect or repair this important barrier to prevent or treat such disorders. This project focuses on developing novel trefoil factor family peptide probes to understand their mechanisms of action in gastrointestinal protection and wound healing.

Understanding a new mechanism for treating asthma

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr Eunice Poon (k.poon@uq.edu.au)

Asthma is a chronic condition which leads to narrowing and inflammation of airways in the lung. Common triggers include allergens such as pollen, dust and mould. There is currently no cure. This project will investigate a protein on the cell surface that is associated with allergic asthma, investigate its mechanistic role in promoting lung inflammation, and help in the development of new therapeutics using a mouse model of lung inflammation.

Understanding bacterial metabolites in immunity

Understanding cellular activation through G protein coupled receptors

Supervisors: Professor David Fairlie (d.fairlie@uq.edu.au), Dr James Lim (j.lim@imb.uq.edu.au)

G protein-coupled receptors are the most common therapuetic target on the cell surface. Understanding how they work involves investigating how specific molecules bind to them, triggering a series of fundamental cellular functions. This project aims to unravel the details of this activation process and potentially identify novel drug targets to treat various diseases.

Understanding how blood vessels in the brain are formed

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

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

Understanding the complex spatial distribution of cone snail venom peptides across the venom gland

Understanding the molecular structures of proteins involved in rare disease.

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

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

Upgrading the potency of a cancer drug using structure-based design

Using venom peptides to understand the function of sensory neurons

Venom-Derived Blood-Brain Barrier Shuttles

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

The blood-brain-barrier (BBB) is a biological barrier that tightly controls the transfer of substances between the blood and the brain. There is evidence that some peptides found in animal venom can pass the BBB via receptor-mediated transcytosis, for example the bee venom peptide apamin. This project aims to identify new venom peptides that can pass the BBB, and develop peptide-based shuttles to transfer cargo across it.

Venom peptide drug discovery

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

Venoms comprise a highly complex cocktail of bioactive peptides evolved to paralyse prey and defend against predators. Homology of prey/predator receptors to human receptors render these venom peptides also active on human receptors and they have become a rich source for neurological tools and therapeutics. This project comprises discovery, synthesis and structure-activity relationship studies of these venom peptides with the goal to develop novel probes for neuroscientists as well as therapeutic drug leads.

Charactering the efficacy of novel chemical entities in multi-drug resistant bacteria

Supervisors: Professor Mark Walker (mark.walker@uq.edu.au); Dr David De Oliveira (d.deoliveira@uq.edu.au)

Antimicrobial resistance (AMR) is currently a significant global health concern and is projected to be the leading cause of death by 2050. Many first, second and last-line antibiotics are no longer effective in the treatment of severe bacterial infection. As such, new antimicrobials are urgently required. Previous work from our group has demonstrated that compounds with a core 8-hydroxyquinolone structure exhibit broad range antimicrobial activity against a spread of clinically relevant drug-resistant bacteria. This Honours project will comprehensively evaluate the antimicrobial efficacy of next-generation, 8-hydroxyquinolone core containing structures against a select range of clinically relevant drug-resistant bacterial pathogens. This research has the potential generate an innovative treatment for patients suffering drug-resistant bacterial infection.

Data mining of antimicrobial activity data from public databases and web-sites.

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

The Community for Open Antimicrobial Drug Discovery (CO-ADD) is maintaining a web-based information system, for the antimicrobial and chemistry data it collected over the last 5 years. The dataset is used to build various machine learning methods for the prediction of antimicrobial activity and enhance the discovery of novel antibiotic against multi-drug resistant pathogen. The project aims to enhance the dataset with additional data from public sources, by using data-mining methods and large language models (like Llama2) to extract structured data from the public sources.

Genetics of biofilms

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

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

How antibiotic resistant uropathogenic E. coli cause urinary tract infection

Supervisors: Professor Mark Schembri (m.schembri@uq.edu.au), Dr Minh-Duy Phan (m.phan1@uq.edu.au)

Urinary tract infections (UTIs) are one of the most common infectious diseases, with a global annual incidence of ~400M 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 use advanced molecular genetics and infection models to examinehow UPEC cause disease and become resistant to antibiotics, with a goal to identify new approaches to treat and prevent infection.

How bacteria build a strong cell envelope

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

Gram-negative bacteria have an outer membrane that is tightly connected with the underlying peptidoglycan cell wall and protects the cell from many toxic molecules and even antibiotics that work against Gram-positive bacteria. We know little about how growing and dividing bacteria coordinate the biogenesis of the outer membrane with the growth of the peptidoglycan layer. The projects will build on our recent discoveries to dissect the dynamic linkages between the outer membrane and peptidoglycan, to identify weaknesses in the assembly process that may be exploited in the future by new antibiotics. The student undertaking the project will learn state-of-the art techniques in microbiology and molecular biology on molecular targets that are of interest for antibiotic drug discovery.

How E. coli cause life-threatening infections in infants

Supervisors: Professor Mark Schembri (m.schembri@uq.edu.au), Dr Nhu Nguyen (kn.nguyen@uq.edu.au)

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

How E. coli cause urinary tract infections

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

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

Investigating the role of host lipids in Salmonella infections

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

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

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

Machine learning in drug discovery - Data mining and validation

Machine learning in drug discovery - Data modelling and prediction

Prediction of resistance profile of bacteria from whole genome sequence

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

A rapid determination if an infection is caused by a drug-resistant pathogens is becoming more and more a medical issue in hospitals. One option is to use whole genome sequencing (WGS) together with machine learning models to predict the resistance profile of the bacteria. The Community for Open Antimicrobial Drug Discovery (CO-ADD) has collected more than 800 multi-drug-resistant bacteria, together with their whole genome sequence and their activity/resistance against antibiotics used in the clinic. The project is to use the collected data and build predictive models, starting from published machine learning methods and develop improved deep learning methods.

Reconstituting key steps in bacterial cell envelope assembly

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

Gram-negative bacteria have a complex cell envelope with a thin peptidoglycan layer and an outer membrane. Different multi-protein machineries expand the peptidoglycan layer during length growth and cell division, and trans-envelope machines export phospholipids, LPS and outer membrane proteins through the peptidoglycan to their final destination in the outer membrane. How these machines work and are coordinated with each other is poorly understood. The project aims to reconstitute key steps in cell envelope biogenesis in the test tube as tools to investigate their structures and functioning, and assay development for the screening for new antibiotic molecules. The student will learn advanced biochemical techniques using membrane systems with complex substrates and advanced assays.

Synthesis of antibiotic-derived conjugates

Synthesis of antibiotic-derived fluorescent probes

The genomic epidemiology of Elizabethkingia anophelis

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

Elizabethkingia anophelis is an opportunistic pathogen capable of causing diverse severe and complex infections, including sepsis and neonatal meningitis. E. anophelis has been linked to prolonged community-associated outbreaks spanning multiple years but is predominantly associated with nosocomial infections, especially among immunocompromised patients and those with underlying comorbidities. Complicating treatment is the inherent resistance of these bacteria to a broad spectrum of antibiotics, including penicillins, β-lactams, β-lactamase inhibitors, cephalosporins, carbapenems, and polymyxins. Consequently, infections caused by E. anophelis exhibit a mortality rate ranging from 18% to 70%. The potential for E. anophelis to establish persistent colonise in individuals is concerning and presents a significant risk for onward transmission, particularly in cases of perinatal vertical transmission from mother to neonate. Despite these concerns the genomics and clinical significance of E. anophelis remains poorly understood. This project provides a unique opportunity for a comprehensive genomic analysis of a clonal lineage within a single individual, improving our understanding of Elizabethkingia infections and revealing how this organism can persistently colonise its host and cause frequent intermittent BSI despite extensive exposure to multiple different antibiotics.

Understanding antibiotic resistance

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

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

Understanding the genetic basis for Salmonella Typhimurium biofilm formation under infection relevant conditions

Supervisors: Dr Jessica Rooke (j.rooke@imb.uq.edu.a u), Professor Ian Henderson (i.henderson@imb.uq.edu.au)

Salmonella enterica is a globally disseminated pathogen that causes infections in humans, animals, and plants. As part of this infectious lifecycle, S. enterica often forms biofilms that are capable of withstanding routinely used antibiotics. Various environmental signals have been shown to induce biofilm formation, and we have identified that host lipids induce robust biofilm formation in vitro. However, the precise mechanism for biofilm formation under these conditions remain unknown. In this project, we aim to elucidate the genetic determinants of S. enterica biofilm formation in response to host lipids, to further understand this phenomenon and to develop novel therapeutics to treat infections that are complicated by biofilm formation.

Using genetics to understand antimicrobial resistance

Supervisors: Professor Ian Henderson (i.henderson@imb.uq.edu.au), Dr Von Torres (v.torres@uq.edu.au)

Antimicrobial resistance (AMR) is a global issue as drug-resistant bacterial infections have been estimated to contribute to at least ~5 million deaths in 2019 alone and is expected to reach 10 million deaths annually by 2050. The genetic mechanisms of drug resistance in bacteria are diverse and complex but elucidating these are vital for developing novel therapeutics and control strategies. Building on previous work, we aim to further explore and validate findings of genes involved in antibiotic resistance in Gram-negative bacteria. The student undertaking this project will learn fundamental concepts in molecular microbiology and use a variety of techniques including: bacterial strain culturing and maintenance, antimicrobial susceptibility testing, phenotypic and biochemical assays.

ALS variant interpretation

Generation of micro organospheres for patient-derived drug screening assays

Genetic Insights into Reproductive Health: Unravelling the Causal Links Between age at Menarche, BMI, Height, and Pregnancy Outcomes

Supervisors: Dr Christopher Flatley (c.flatley@uq.edu.au)

Menarche, the onset of a woman's reproductive capacity, typically occurs between the ages of 10 and 16 years. This pivotal stage, marked by the onset of menstruation, signifies a period of profound biological development that has lasting implications for later-life health outcomes. Studies suggest an earlier onset of menarche is associated with adverse pregnancy outcomes, including preterm birth and low birth weight. However, unravelling the intricate causal relationships between menarche and pregnancy outcomes remains a challenge, partly due to the complex relationships with body size. For example, there are established biological mechanisms linking earlier age at menarche with higher adult BMI and shorter stature. Additionally, both elevated BMI and shorter stature independently contribute to the adverse pregnancy outcomes. Using a genetic statistical method called Mendelian Randomization, this project will investigate the causal relationships between age of menarche, BMI, height and pregnancy outcomes. Insights gained from this research have the potential to inform public health initiatives and healthcare policies, ultimately fostering a better understanding of the factors influencing pregnancy complications.

Grey-matter atrophy in Alzheimer's disease

Supervisors: Dr Baptiste Couvy-Duchesne (b.couvy-duchesne@imb.uq.edu.au)

One project will involve the analysis of a large neuroimaging cohort, which contains thousands of elderly individuals imaged using MRI. Our lab develops statistical methods for the analysis of fine-grained brain images, which will be applied to analyse this cohort. Our approach allows refining the traditional neuroimaging analyses, that have been performed at a region of interest level, which can miss some of the fine-grained brain variation. The results will contribute to our current large-scale initiative that combines results from all continents, to create a high-resolution map of the brain regions associated with Alzheimer’s disease as well as with specific functional and cognitive domains. In particular, the student will perform neuroimaging analyses of one or several memory domains available in the cohort (e.g. WAIS-R Digit Symbol, WAIS-R Digit Span, WMS-R Logical Memory, Boston Naming Test). We expect the fine-grained brain map to refine our current understanding of the grey-matter regions associated with cognition domains.
The methods and software we use are shared with the field of genetics/genomics, meaning the student will acquire highly transferrable skills and knowledge. In addition, the dynamic environment of the program in complex trait genomics (PCTG), will support the student to to enrich their knowledge in the fast-paced / rapidly-evolving field of computational neuroimaging and human genetics.

We encourage applicants with scientific background, but most importantly with a strong inclination for problem solving and computational work.

Hypergraph-based integration of multi-omics data to prioritise candidate genes for drug repurposing

Supervisors: Dr Gagendeep Singh (g.singh@imb.uq.edu.au); Dr Sonia Shah (sonia.shah@imb.uq.edu.au)

Experimental discovery of a new drugs is time consuming and expensive process. However, several recent studies stated that drug repurposing which aims to identify novel indications from already existing drugs would be helpful with less risk and cost. Although, several methods are available for drug repurposing based on expression profiles. But selection of potential candidate genes for drug repurposing based on network approaches is still lacking. Thus, in this study, we aim to explore disease associated risk genes based on networks-based approaches such as gene-regulatory networks, drug-target interactions, drug-drug interactions, and pathway-based interactions using computational means. It is crucial to understand the cross-talks among the interacting genes regulating several pathways which ultimately results in side effects after drug dosages. This systemic analysis might be helpful in selection of key candidate genes for drug repurposing to deal with genetic associated diseases effectively.

Imputation of neuropsychological scores across multi-cohort data using machine learning

Supervisors: Dr Baptiste Couvy-Duchesne (b.couvy-duchesne@imb.uq.edu.au)

This project will focus on imputing neuropsychological scores using multi-cohort data. We have gathered 10+ neuroimaging cohorts of elderly individuals and each cohort has collected a (sub)set of neuropsychological batteries. Some scales have been very often collected (e.g. MMSE), and some have been only collected in a handful of cohorts (e.g. MoCA, or Boston Naming Test). A recent article from collaborators in Newcastle (https://doi.org/10.1002/dad2.12453), has shown that it is possible to impute some of the missing cognitive scores, by leveraging information nad items from the collected scores. Such imputation would be highly beneficial to boost power of downstream neuroimaging analyses. The student will perform and evaluate the neuropsychological score imputation, on some of our available cohorts. The project would include application of machine learning techniques, and interpretation of the prediction algorithms (i.e. which items are used in imputation). Beyond an efficient imputation, validation of the prediction algorithms based on the theory of cognitive processes, would increase confidence in the imputation process.

Increasing drug success rate in human clinical trials using genomics

Supervisors: Dr Sonia Shah (sonia.shah@imb.uq.edu.au)

Around 90% of drug candidates fail in human clinical trials largely due to lack of efficacy or safety concerns. This partly reflects the limitations of using in vitro and animal studies to predict the effect of compounds in humans. Recent studies highlight that drug targets backed by evidence from human genetic studies are 2 times more likely to make it to market. Human genetic data can also identify potential adverse side effects. Such information prior to embarking on human clinical trials could improve the success rate of a compound in human clinical trials and help avoid adverse outcomes for participants.

This project will use statistical genomics analyses using publicly available human genomic data to predict efficacy as well as any safety concerns of compounds that are currently in the drug development pipeline.,

Skills: Familiarity with computational analyses (e.g using R or python etc) is needed for this project

Project significance: Findings from this project could potentially identify new therapeutic applications for these compounds or unknown side effects, and ultimately informing future human clinical trials.

Supervisors: You will be working with a multidisciplinary team of supervisors Prof Dave Evans, Dr Sonia Shah, Prof Glenn King, Assoc/Prof Nathan Palpant

Investigating the genetic basis of left-handedness

Supervisor: Professor David Evans (d.evans1@uq.edu.au)

This project will involve latent class analysis of handedness, footedness and ocular dominance data in 10,000 children from the Avon Longitudinal Study of Parents and Children. The student will then investigate the genetic aetiology of these latent classes including how known variants for left handedness and ambidexterity relate to them.

Investigation of cell types found in patient-derived organoids

Large scale neuroimaging study of Alzheimers’ disease

Supervisors: Dr Baptiste Couvy-Duchesne (uqbcouvy@uq.edu.au)

This project will involve the analysis of a large neuroimaging cohort from the US, which contains more than 10,000 individuals imaged using MRI. Our lab develops statistical methods for the analysis of fine-grained brain images, which will be applied to analyse this cohort. The results will contribute to our current large-scale initiative that combines results from all continents, to create a high-resolution map of the brain regions associated with Alzheimer’s disease status and risk. The methods and software we use are shared with the field of genetics/genomics, meaning the student will acquire highly transferrable skills and knowledge. In addition, the dynamic environment of the program in complex trait genomics (PCTG), will support the student to to enrich theirknowledge in the fast-paced / rapidly-evolving field of neuroimaging and human genetics.

We encourage applicants with a scientific background, but most importantly with a strong inclination for problem solving and computational work. We recognise the richness of Indigenous cultures and the unique knowledge Aboriginal and Torres Strait Islander employees bring to our workplace. We welcome and encourage applications from Aboriginal and Torres Strait Islander people. We encourage applications from individuals with disabilities, culturally and linguistically diverse individuals, and individuals from the LGBTIQA+ community. If you have accessibility requirements, please note them in your application and we will endeavour to make any reasonable adjustments.

Navigating the genetic landscape of neurodegenerative disease: Evaluating Variant Prioritisation Tools for Precision Medicine

Supervisor: Dr Fleur Garton (f.garton@imb.uq.edu.au)

Amyotrophic Lateral Sclerosis is a fatal neurodegenerative condition with a complex genetic architecture. Whole genome and exome sequencing supports the identification of both common and rare variants contributing to disease. Rare variants in known ALS genes have often not been seen before and are labelled as variants of uncertain significance. As more samples are analysed this number becomes larger and prioritising the variants to follow-up is necessary. In-silico prediction tools exist for this purpose. They use empirical data to predict their likelihood to be deleterious but their sensitivity for ALS has not yet been explored.

The project will test the sensitivity known pathogenic ALS and benign ALS variants across a range of in-silico tools. We hypothesise that certain tools have better sensitivity at detecting pathogenicity, and these are the tools that the community should be used to prioritise variants of unknown significance.

This is a computational project that will require you to understand human genome nomenclature. It will involve variant annotation and analysis. You will be involved in comparing tools using a range of software tools and packages with analyses performed in R. You will use a variety of statistical methods to make conclusions. This may reveal future opportunities for variant interpretation (i.e. critical assessment of proposed oligogenic genetic architecture) and/or sensitivity testing for other conditions.

Within the dynamic environment of the program in complex trait genomics (PCTG), you will be supported and encouraged to enrich your knowledge in the fast-paced / rapidly-evolving field of human genetics.

Personalised nutrition

Understanding sex-specific cardiovascular disease risk

Validation of synthetic Matrigel's for the growth of 3D endometrial organoids

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