Centre for Cell Biology of Chronic Diseases

Supervisor: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au), Dr Xiaoli Chen (x.chen8@uq.edu.au)

Ageing is the primary risk factor for many degenerative diseases. This project aims to advance a synthetic protein technology designed to selectively silence age- and disease-associated gene regulatory elements, with the goal of restoring healthier gene expression programs and improving cellular function and fitness.

Supervisor: Dr Larisa Labzin (l.labzin@uq.edu.au)

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

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

Cardiovascular disease does not result from a single genetic change or environmental stress. It emerges from interactions between genetic background, cell state, ageing, metabolism, comorbid disease and environmental exposures, yet conventional laboratory models often isolate these factors rather than recreating their combined effects. Our laboratory is interested in a central question: how can we build human models that better reflect the biological complexity that determines disease risk and treatment response?

This HDR project will develop and apply advanced human pluripotent stem-cell models to study cardiovascular disease in a more realistic and population-relevant context. A major focus is the 'village-in-a-dish' approach, which enables many genetically distinct human induced pluripotent stem-cell lines to be cultured and analysed together. This creates a scalable system for linking inherited genetic variation with cellular phenotypes and for testing why different individuals respond differently to the same biological stress or therapeutic intervention (Nature Communications 2023).

The project will also build on our work to improve the maturation and physiological relevance of human cardiomyocyte models. Depending on the student's interests, this may include manipulating metabolic environment, contractile state, tissue architecture or exposure to clinically relevant stresses such as hypoxia, acidosis and reperfusion injury. The aim is to move beyond simplified cell culture systems towards models that better reproduce adult cardiac physiology and disease-associated vulnerability.

A second major theme is comorbidity modelling. Cardiovascular risk is strongly influenced by conditions such as diabetes and metabolic dysfunction, but these factors are rarely incorporated into preclinical models in a systematic way. Our laboratory has shown that glycaemic variability can directly impair cardiomyocyte function and increase susceptibility to myocardial injury, providing a framework for modelling how metabolic instability contributes to cardiovascular risk (Nature Communications 2026).

The project may combine stem-cell differentiation, population-scale cellular models, genome engineering, single-cell genomics, metabolic profiling, electrophysiology, contractility assays and high-throughput phenotyping. There are also opportunities to integrate experimental findings with human genetic and clinical datasets.

The longer-term goal is to create human disease models that are sufficiently realistic to predict patient biology, helping explain variation in disease severity, identify mechanisms of vulnerability and improve how new cardiovascular therapies are developed and tested.
 

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.

Supervisor: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au), Dr Marina Naval Sanchez (m.navalsanchez@imb.uq.edu.au), Jingyu Zhang (jingyu.zhang@uq.edu.au)

Our recent work showed that ageing is associated with the activation of AP-1-bound chromatin regions that are epigenetically silenced in young cells. This project will use cell-based and in vitro approaches to determine how AP-1 interacts with different layers of epigenetic repression to progressively unlock chromatin during ageing.

Supervisor: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au), Dr Ralph Patrick (ralph.patrick@imb.uq.edu.au)

This dry lab project will leverage single-cell multiome and DNA methylation datasets to investigate how early-life stress, or its absence, shapes growth trajectories, developmental potential, and adult fitness. The findings may provide insights relevant to both human health and disease and the livestock industry.

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

Heart failure affects tens of millions of people worldwide, yet many patients continue to have symptoms because existing therapies do not directly correct the mechanical abnormalities of the heart muscle itself. This is particularly important in heart failure with preserved ejection fraction (HFpEF), where impaired relaxation and abnormal filling remain major therapeutic challenges. Our laboratory is asking: can the molecular machinery that controls cardiac contraction and relaxation be targeted directly to create a new class of heart failure medicines?

This HDR project will focus on the development of macrocyclic peptide therapeutics that act on the cardiac troponin complex, a central regulator of muscle contraction. Our laboratory has identified de novo macrocyclic peptides that selectively alter troponin dynamics and improve myocardial relaxation without compromising contractile function, establishing a new therapeutic strategy for diseases in which cardiac relaxation is impaired (Angewandte Chemie, in press).

The project will investigate how these molecules bind to and regulate the contractile apparatus, how their effects vary across disease-relevant physiological states, and how lead compounds can be optimised for therapeutic development. Depending on the student's interests, the work may combine peptide discovery and screening, protein biochemistry, structural modelling, sarcomere biophysics, human stem-cell-derived cardiomyocytes, engineered cardiac tissues, functional phenotyping and translational pharmacology.

A major strength of the project is its direct connection to a growing translational program. The discoveries have generated new intellectual property, secured a A$1.5 million MRFF CUREator award and venture investment, and led to the establishment of Rosella Therapeutics, a biotechnology company focused on advancing first-in-class macrocyclic peptide medicines for cardiovascular disease. This provides opportunities for HDR students to work at the interface of academic discovery, biotechnology and drug development, gaining exposure to the steps required to move a therapeutic concept towards clinical translation.

The broader scientific aim is to establish whether direct modulation of the cardiac contractile machinery can overcome limitations of current heart failure treatments. Beyond HFpEF, the platform may also create opportunities to target other diseases characterised by abnormal myocardial contraction or relaxation.

The longer-term vision is to develop a new therapeutic modality for cardiovascular disease, taking discoveries from molecular mechanism through human disease models, drug optimisation and ultimately clinical development.
 

Supervisor: Dr Nicholas Ariotti (n.ariotti@uq.edu.au)

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

Using mesenchymal stromal cells-derived EVs, we will explore the inhibition of the inflammatory response during ECMO.

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

Inherited cardiovascular diseases such as cardiomyopathies can have devastating consequences for patients and their families, yet genetic testing often identifies rare DNA variants whose clinical significance remains uncertain. This creates a major challenge: a genetic change may be detected, but clinicians may still not know whether it causes disease, how it alters heart function, or what it means for other family members. Our laboratory is interested in closing this gap by asking: which rare genetic variants truly cause cardiovascular disease, how do they disrupt cardiac biology, and can those effects ultimately be reversed?
This HDR project will investigate candidate disease-causing variants identified through clinical genetics and genomic studies. Our program has already examined variants in genes including HOPX, TPM1 and TNNC1, using functional evidence to connect genotype with cardiac phenotype. This work identified HOPX as a novel cardiomyopathy-associated gene and contributed to reclassification of the TNNC1 E96del variant from a Variant of Uncertain Significance to Likely Pathogenic, providing clinically actionable information for diagnosis, family screening and patient management.
A major strength of the project is the ability to recreate human genetic disease experimentally. Depending on the variant and student interests, the work may combine patient-derived or genome-engineered human pluripotent stem cells, cardiomyocyte differentiation, genome editing, single-cell genomics, cardiac functional phenotyping and molecular biology. These systems allow candidate variants to be introduced or corrected in controlled genetic backgrounds, making it possible to determine whether a variant is causal and define precisely how it changes cardiomyocyte development, structure, contractility or stress responses.
The project can also extend beyond diagnosis to ask whether disease-associated phenotypes are therapeutically reversible. Once the underlying mechanism is established, candidate interventions can be tested in human cardiac models, creating a pathway from genetic diagnosis to mechanism-based therapeutic development. This reflects the laboratory's broader strategy of linking human genetics with experimentally tractable disease models rather than treating variant interpretation as a purely computational problem. Our stem-cell and single-cell studies have already established platforms for defining cardiac developmental trajectories and genetic mechanisms of disease (Cell Stem Cell 2018).
The work also sits within a broader national effort to improve rare-disease genomics. Through the Australian Functional Genomics Network, this research area has contributed to evaluation of nearly 250 variants of uncertain significance, including variant reclassifications, new gene-disease associations and resolved diagnoses.
The longer-term goal is to move from variant discovery -> biological mechanism -> clinical interpretation -> therapeutic opportunity, improving the value of genomic testing for patients and families affected by inherited cardiovascular disease.

Supervisor: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au), Dr Xiaoli Chen (x.chen8@uq.edu.au)

Transcription factor networks are central regulators of cell function and become dysregulated during ageing and disease. This project will use RNA-based technologies and AAV-mediated approaches to reprogram disease-associated transcription factor networks, with the aim of restoring aged and diseased mouse livers towards a healthier, more functional state.

Supervisors: Professor Alpha Yap (a.yap@uq.edu.au), Dr Ivar Noordstra (i.noordstra@imb.uq.edu.au)

Supervisors: Professor Alpha Yap (a.yap@uq.edu.au), Dr Kinga Duszyc (k.duszyc@imb.uq.edu.au)

Supervisor: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au), Dr Ralph Patrick (ralph.patrick@imb.uq.edu.au)

This computational biology project will leverage established human single-cell datasets to identify transcription factors that drive age-related diseases. The project will also investigate whether common regulatory drivers are shared across different disease states, potentially revealing conserved mechanisms of human ageing and disease.

Supervisors: Dr Harriet Lo (h.lo@imb.uq.edu.au), Dr Tom Hall (thomas.hall@imb.uq.edu.au)

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

Supervisor: Dr Larisa Labzin (l.labzin@uq.edu.au)

Supervisor: Dr Igor Bonacossa Pereira (i.bonacossapereira@uq.edu.au), Professor Rob Parton (r.parton@imb.uq.edu.au)

In this project, we aim to discover how defensive lipid droplets function and what are their essential components. To study this, we have established an infection model using Salmonella or nematode-pathogenic E. coli in the genetically tractable roundworm C. elegans.

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

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.

Supervisors: Dr Tom Hall (thomas.hall@imb.uq.edu.au), Dr Harriet Lo (h.lo@imb.uq.edu.au)

The results of genetic testing in humans are often difficult to interpret. This project will use live imaging and CRISPR/Cas9 technology to introduce human variants into zebrafish and examine the effects on muscle and adipose tissue.

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.

Supervisor: Associate Professor Anne Lagendijk (a.lagendijk@imb.uq.edu.au), John Kemp

This project will utilise CRISPR/Cas9 to develop a pls3 zebrafish knockout strain. We will define how pls3 regulates blood vessel and bone development using high-end in vivo live imaging approaches.

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

Common diseases such as diabetes, cardiovascular disease and inflammatory disorders are usually treated as single diagnoses, yet patients with the same condition can have very different underlying biology, clinical trajectories and responses to treatment. A central question for our laboratory is therefore: can inherited genetic risk be decomposed into distinct biological mechanisms that reveal meaningful disease subtypes?

This HDR project will investigate how the epigenomic programs that govern cell identity can be used to interpret the enormous number of genetic variants associated with complex disease. Our laboratory has identified conserved regulatory principles that organise coding and non-coding regions of the genome and help connect genetic variation with the genes, cell types and biological processes it affects (Cell Systems 2020; Nucleic Acids Research 2025). These discoveries provide the conceptual foundation for EpiCops, a computational framework designed to resolve complex genetic risk into distinct regulatory programs rather than treating all associated variants as contributing to a single homogeneous disease process.

The project will use large-scale human genomic and clinical datasets to ask whether genetically defined regulatory programs correspond to different disease mechanisms, tissue and cell-state dependencies, clinical outcomes or therapeutic responses. Initial applications are focused on cardiometabolic diseases such as type 2 diabetes and myocardial infarction, but the framework is disease-agnostic and can be extended across a wide range of complex traits.

Depending on the student's interests, the project may combine statistical genetics, machine learning, epigenomics, regulatory genomics, polygenic risk modelling, single-cell data analysis and clinical cohort studies. There are also opportunities to integrate computational predictions with experimental validation using human stem-cell models and functional genomics, allowing disease subtypes identified in population data to be linked back to measurable cellular mechanisms.

The translational potential is substantial. Related genomic platforms developed by the laboratory have already attracted more than A$1 million in commercial research partnerships with HAYA Therapeutics, Merck, CSL and Sanofi, supporting applications in therapeutic target discovery and genetically informed patient stratification.

The longer-term vision is to move beyond broad diagnostic labels towards a mechanism-based classification of complex disease. By linking inherited genetic variation with regulatory biology, cellular context and clinical outcomes, this project aims to identify patient groups who share common disease mechanisms, reveal new therapeutic targets and ultimately improve how patients are stratified for prevention and treatment.
 

Supervisor: Professor Matt Sweet (m.sweet@imb.uq.edu.au)

Supervisor: Professor Matt Sweet (m.sweet@imb.uq.edu.au)

Supervisor: Dr Robert Ju (r.ju@uq.edu.au)

Supervisor: Associate Professor Frederic Gachon (f.gachon@uq.edu.au)

Supervisors: Professor Brett Collins (b.collins@imb.uq.edu.au), Dr Michael Healy (m.healy@imb.uq.edu.au)

Supervisors: Dr Ye-Wheen Lim (y.lim@uq.edu.au), Professor Rob Parton (r.parton@imb.uq.edu.au)

How are nanoparticles transported across different biological barriers from the bloodstream to their target sites? This project will use tumor xenograft models and live imaging in the zebrafish to uncover the trafficking of nanoparticles in a live organism.

Supervisors: Dr Yeping Wu (yeping.wu@imb.uq.edu.au), Professor Rob Parton (r.parton@imb.uq.edu.au)

Caveolae, microscopic pits on the surface of animal cells, have been linked to many human cancers. This project will use genome-edited cell models and confocal microscopy to investigate the roles of caveolar components in cellular pathways involved in cancer development. It will provide training in advanced microscopic techniques and cellular assays linked to tumour cell proliferation and migration.

Supervisor: Dr Igor Bonacossa Pereira (i.bonacossapereira@uq.edu.au), Professor Rob Parton (r.parton@imb.uq.edu.au)

This project aims to discover non-caveolar functions of caveolins using a nematode model. Caveolins together with cavins  are key molecules that mould flask-like plasma membrane invaginations called caveolla. The functions of this structure include functioning as a membrane reservoir to buffer stretch, microdomains organizers, and alternative endocytic entry points. While caveolins exist within caveola, they are also found in the membrane of cells that lack this structure such as nerve cells and some immune cells. In this context, the function of caveolins is unknown. In this work, we will make use of state-of-the-art microscopy and CRISPR-mediated gene editing to probe the C. elegans and human caveolins to characterize their function in a living animal that naturally does not have caveola.  

Supervisors: Dr Harriet Lo (h.lo@imb.uq.edu.au), Professor Rob Parton (r.parton@imb.uq.edu.au)

Tardigrades are one of the toughest creatures on earth. In this project we will study the cellular adaptations that allow tardigrades to survive in extreme conditions.

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

Heart attacks do not affect everyone in the same way. Two people with similar conventional cardiovascular risk can differ markedly in whether they experience myocardial infarction, how much heart muscle is damaged and how well they recover after treatment. A central question for our laboratory is therefore: how much of this variation is inherited, and can genetic differences be used to predict myocardial vulnerability and treatment response?

This HDR project will investigate the genetic and cellular mechanisms that determine susceptibility to myocardial infarction and the severity of injury once a heart attack occurs. Rather than treating cardiovascular risk as a single additive process, we are interested in identifying biologically distinct pathways of risk that may predispose individuals to disease through different mechanisms. These mechanisms may influence the likelihood of developing a heart attack, the intrinsic sensitivity of cardiomyocytes to ischaemic injury, or the effectiveness of cardioprotective therapies.

A major component of the project will integrate human genetics with population-scale stem-cell biology. Our laboratory and collaborators have developed 'village-in-a-dish' approaches that allow genetically diverse human induced pluripotent stem-cell lines to be studied together at scale, enabling direct mapping between inherited genetic variation and cellular phenotypes (Nature Communications 2023). These approaches are now being extended to human cardiomyocytes to determine whether genetic background influences responses to hypoxia, acidosis, metabolic stress and ischaemia-reperfusion injury.

Depending on the student's interests, the project may involve statistical genetics, polygenic and pathway-based risk modelling, EpiCops disease subtyping, human pluripotent stem-cell differentiation, single-cell genomics, genome engineering and high-throughput cardiac phenotyping. The goal is to connect genetic signals identified in large human populations with experimentally measurable differences in myocardial injury and recovery.

The translational opportunity is substantial. Our laboratory has already progressed a first-in-class cardioprotective therapeutic targeting ASIC1a from discovery through Phase I clinical evaluation, with further trials in myocardial infarction underway or planned. This creates an opportunity to ask whether inherited biology can help identify which patients are most likely to benefit from cardioprotective treatment.

The longer-term vision is to move beyond treating all heart attacks as biologically equivalent. By linking genetic risk, myocardial vulnerability and therapeutic response, this project aims to help develop more precise ways to predict cardiovascular injury, identify high-risk patients and ultimately personalise cardioprotective therapy.

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

Heart attack remains a major cause of death and disability worldwide because restoring blood flow does not completely prevent irreversible damage to heart muscle. During ischaemia, loss of oxygen forces cells to rely on anaerobic metabolism, causing lactate accumulation and a rapid fall in tissue pH. Our laboratory is interested in a fundamental question arising from this process: how does tissue acidosis become a signal for cell injury and death, and can these mechanisms be targeted to protect the heart?

A major focus is the acid-sensing ion channel ASIC1a, which our laboratory identified as an important mediator of cardiomyocyte death during ischaemia-reperfusion injury. Blocking ASIC1a preserves cardiomyocyte viability and improves cardiac recovery in experimental models, discoveries that established ASIC1a as a first-in-class cardioprotective target and have progressed into clinical development through Infensa Bioscience (Circulation 2021; European Heart Journal 2024).

This HDR project will investigate the broader biology of acid-sensitive stress responses in cardiovascular disease. Key questions may include: Which cardiac cell types activate acid-sensing pathways during ischaemia? How do the magnitude and duration of acidosis determine whether cells recover or die? How do genetics, metabolism and comorbidities modify these responses? And can acid-sensitive mechanisms be exploited not only therapeutically, but also as biomarkers of evolving tissue injury?

Depending on the interests and background of the student, the project can combine human pluripotent stem-cell-derived cardiomyocytes, genome engineering, functional genomics, high-content cellular phenotyping, transcriptomics, human genetics and experimental models of myocardial infarction. There are also opportunities to investigate the spatial and temporal activation of ASIC1a during tissue injury and to evaluate new peptide-based probes and inhibitors as diagnostic or therapeutic tools. The broader research program is examining these mechanisms across multiple ischaemic settings, including myocardial infarction and organ transplantation.

The project sits at the interface of fundamental cardiovascular biology and therapeutic translation. Its longer-term aim is to identify the molecular events that determine whether ischaemic tissue survives or progresses to irreversible injury, and to use that knowledge to develop new strategies for protecting patients from the consequences of heart attack and other forms of acute ischaemia.

Supervisor: Professor Matt Sweet (m.sweet@imb.uq.edu.au)