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Centre for Cell Biology of Chronic Diseases

Advancing 3D imaging and visualisation of cell surfaces

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

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

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

Blocking nutrient uptake to limit cancer cell survival

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

Cancer metastasis and stem-like reprogramming via mechanical signatures

Supervisors: Dr Samantha Stehbens (s.stehbens@uq.edu.au), Dr Melanie White (melanie.white@imb.uq.edu.au)

Tumour cells spread via the circulation. Here, travelling as clusters facilitates their survival and ability to seed into new tissues. This project will investigate how tumour cells form clusters and the role of physical forces.

Circadian regulation of protein glycosylation

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

Controlling cell fate through transcription factor-based reprogramming

Supervisor: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au)

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

Supervisor: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au)

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

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

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.

Fighting infection: Enhancing phagocytosis and pathogen killing

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

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

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

How cytokines increase sensitivity to inflammation triggered by apoptosis in epithelia

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

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

Supervisors: Dr Samantha Stehbens (s.stehbens@uq.edu.au), Dr Melanie White (melanie.white@imb.uq.edu.au), Dr Meg McFetridge

Melanoma spreads from the skin to the brain. The brain is a unique environment, both biochemically and physically. This project will explore the role of the physical environment in mediating the survival and spread of melanoma to the brain.

How immune cells eat and digest pathogens; phagocytosis

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

Immune navigation: changing signals to control inflammation in disease

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

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

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.

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 blood vessel formation and function

Supervisors: Dr Emma Gordon (e.gordon@imb.uq.edu.au), Dr Lilian Schimmel (l.schimmel@imb.uq.edu.au)

The research within the Gordon lab is focused on the formation and maintenance of the blood vascular system. Vessels form complex branched networks that supply oxygen and nutrients to all body tissues. The signals controlling blood vessel growth, identity and migration are all downstream of a single, common complex at the cell surface, yet exactly how these signals mediate a diverse range of functions, depending on the physiological need, remains unknown.

Using biochemistry and microscopy, this project will examine how the extracellular environment is involved in directing the signals from the common cell surface complex to mediated either blood vessel growth, identity, or migration.

Investigating the role of the vasculature in COVID-19

Supervisors: Dr Emma Gordon (e.gordon@imb.uq.edu.au), Dr Larisa Labzin (l.labzin@uq.edu.au)

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

Supervisor: Dr Christian Nefzger (c.nefzger@imb.uq.edu.au)

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

Supervisor: Dr Mel White (melanie.white@imb.uq.edu.au)

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

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.

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

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

Role of macrophage metabolism in driving inflammation

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

Role of macrophage metabolism in host defence against bacterial infections

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

Screening for metastasis inhibitory markers in cancer

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

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

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

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

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

Targeting Nanoparticles to Fight Cancer

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.

Targeting stress and protein quality control pathways in skeletal muscle disease

Supervisors: Dr Amy Hanna (a.hanna@imb.uq.edu.au), Dr Nathan Palpant (n.palpant@uq.edu.au)

Skeletal muscle is an active, highly dynamic tissue that is constantly synthesizing 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 proposal will examine the factors that regulate protein folding in skeletal muscle and determine how the accumulation of misfolded proteins affects muscle contraction and relaxation. Our work will also determine whether these stress pathways are a viable target for treating congenital myopathy by testing novel pharmacological agents in disease models.  

The role of caveolae in cancer

Supervisors: Dr. Kerrie-Ann McMahon (k.mcmahon@imb.uq.edu.au), Dr. Yeping Wu (yeping.wu@imb.uq.edu.au)

Caveola mutations or dysfunction have been linked to human diseases including cancer. 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.

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

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

Microtubules are required for tumour cells to invade tissues. Disruption of microtubules results in cell rupture during invasion. This project will determine if melanoma cells secrete factors to elicit an immune response.

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

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.

Zinc toxicity as an antimicrobial weapon of macrophages

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

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