Investigating novel factors that can inhibit the formation of stroke-prone vascular malformations

Cerebral Cavernous Malformation (CCM) is a progressive vascular disease whereby focal clones of defective endothelial cells give rise to distinctive bulging vascular lesions. The endothelial cells in progressed lesions show reduced adhesion with each other as well as cellular thinning and spreading. CCM lesions form exclusively in venous vessels of the central nervous system (CNS: brain and spinal cord), at a surprisingly high frequency of up to 0.5% of the population. Due to their location and fragile structure CCMs cause chronic headaches, seizures, and haemorrhagic stroke. There are no effective drug treatments available for CCM, meaning that, depending on lesion size, number, and location, surgery is required. 

Both genetic and sporadic forms of CCM disease are induced by somatic second-hit mutations in one of three CCM genes: CCM1, CCM2, or CCM31,2. In mutated ECs, uncontrolled KLF2/4 transcription factor activity has been proven to drive CCM disease. But there is a key, unsolved paradox: in patients, aberrant KLF transcription is found across vascular beds, yet the disease manifests almost exclusively in venous vessels of the CNS. 

We recently identified novel factors that are is downregulated in CCM disease, and when these factors are fully absent CCM phenotypes worsen.

This project will capitalise on our accumulating evidence and investigate these new players using zebrafish and 3D vessel-on-a-chip models to determine how these can prevent CCM progression. 

This project will be supervised by Dr Anne Lagendijk at the Institute for Molecular Bioscience of the University of Queensland (UQ). 

UQ is part of the Go8 and UQ’s strategic plan includes considerable emphasis on research excellence, which ensures a stable and globally competitive environment for this research. The IMB is a recognised world-class research institute with world-leading expertise in cardiovascular and cell biology.

The team has access to UQ/IMB’s state-of-the-art facilities, including ACRF’s Imaging Facility at the IMB (with essential confocal microscopes and a Dragonfly spinning disc), a large Zebrafish Facility, and the Australian National Fabrication Facility (ANFF) for engineering 3D devices. 

This is an Earmarked scholarship project that aligns with a recently awarded Australian Government grant.

The scholarship includes:

• living stipend of $35,000 per annum tax free (2024 rate), indexed annually
• your tuition fees covered
• single overseas student health cover (OSHC).

Learn more about the Earmarked scholarship.

You must contact the principal supervisor for this project to discuss your interest. You should only complete the online application after you have reached agreement on supervision.

Always make sure you are approaching your potential supervisor in a professional way. We have provided some guidelines for you on how to contact a supervisor.

Your application will be assessed on a competitive basis taking into account your:

• academic record
• publication record
• honours and awards
• employment history.

Working knowledge of of cardiovascular or developmental biology would be of benefit to someone working on this project. Desirable (but not required) experience in Model organisms, preferably zebrafish, 3D cell culture techniques, cell transfection, Molecular biology, Image analysis software; ImageJ, Matlab.

You'll demonstrate academic achievement in the field of Cardiovascular or developmental biology and the potential for scholastic success.

A background or knowledge of Cardiovascular or developmental biology is highly desirable.

This project requires candidates to commence no later than Research Quarter 4, 2024. To allow time for your application to be processed, we recommend applying no later than 30 June, 2024 31 March, 2024.

You can start in an earlier research quarter. See application dates.

Before you apply

1. Check your eligibility for the Doctor of Philosophy (PhD).
2. Prepare your documentation.
3. Contact Dr Anne Lagendijk (a.lagendijk@imb.uq.edu.au) to discuss your interest and suitability.

When you apply

You apply for this scholarship when you submit an application for a PhD. You don’t need to submit a separate scholarship application.

In your application ensure that under the ‘Scholarships and collaborative study’ section you select:

• My higher degree is not collaborative
• I am applying for, or have been awarded a scholarship or sponsorship
• UQ Earmarked Scholarship type.

Apply now