Investigating the functions of pericyte-associated microglia in health and Alzheimer’s disease

About the research project

Microglia are a central nervous system (CNS) resident cell with multiple functions including protecting the brain from injury, sculpting neuronal circuitry and providing trophic support for other brain cells. A large proportion of microglia exist in close proximity to brain blood vessels and within the last few years there has been increased interest in their function. In particular, recent evidence indicates microglia may influence CNS blood flow^{1, 2} and suggests they could also play a role in blood-brain-barrier (BBB) integrity in health and disease³. We recently discovered a significant proportion of microglia associated with pericytes, a cell type that exists on the walls of capillaries. We termed these cells pericyte-associated microglia (PEM)⁴. Pericytes are contractile cells and our evidence suggests PEM may indirectly control blood flow via pericytes⁴. Furthermore, we have evidence suggesting PEM number is reduced in Alzheimer’s disease, which may lead to a loss of PEM function⁴. To investigate the role of PEM in cerebral blood flow (CBF) regulation, this project will first investigate if microglia influence CBF indirectly via pericytes by imaging blood flow in mice using in vivo two-photon microscopy through cranial windows at sites of PEM. To establish if PEM alter CBF in response to stimulation, the project will stimulate CBF using neurovascular coupling. Next, this experiment will be replicated in mouse models of Alzheimer’s disease (AD), to determine if PEM function is influenced by AD pathology. This study will uncover novel functions of PEM, which will deepen our understanding of CBF control mechanisms in health, and understand how they break down in AD, potentially opening new avenues of therapeutic development for this debilitating disease.  

References

1.  Bisht K, Okojie KA, Sharma K, et al. Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice. Nature Communications 2021; 12: 5289. DOI: 10.1038/s41467-021-25590-8.
2.  Császár E, Lénárt N, Cserép C, et al. Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions. J Exp Med 2022; 219 20220224. DOI: 10.1084/jem.20211071.
3.  Haruwaka K, Ikegami A, Tachibana Y, et al. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nature Communications 2019; 10: 5816. DOI: 10.1038/s41467-019-13812-z.
4.  Morris GP, Foster CG, Courtney J-M, et al. Microglia directly associate with pericytes in the central nervous system. Glia 2023; 71: 1847-1869. DOI: https://doi.org/10.1002/glia.24371.

Primary supervisor

Meet Doctor Gary Morris

Funding

Applicants will be considered for a Research Training Program (RTP) scholarship or Tasmania Graduate Research Scholarship (TGRS) which, if successful, provides:

• a living allowance stipend funded by University of Tasmania of $34,315 per annum for 3.5 years
• a relocation allowance of up to $2,000
• a tuition fees offset covering the cost of tuition fees for up to four years (domestic applicants only)

A tuition fee offset may be offered to eligible international applicants following competitive assessment 

As part of the application process you may indicate if you do not wish to be considered for scholarship funding.

Other funding opportunities and fees

For further information regarding other scholarships on offer, and the various fees for undertaking a research degree, please visit our Scholarships and fees on research degrees page.

Eligibility

Applicants should review the Higher Degree by Research minimum entry requirements.

Ensure your eligibility for the scholarship round by referring to our Key Dates.

Additional eligibility criteria specific to this project/scholarship:

• Applicants must be able to undertake the project on-campus

Selection criteria

The project is competitively assessed and awarded. Selection is based on academic merit and suitability to the project as determined by the College.

Additional desirable selection criteria specific to this project:

• Experience with animal work
• Experience with immunohistochemistry

Application process

1. Select your project, and check that you meet the eligibility and selection criteria, including citizenship;
2. Contact Doctor Gary Morris to discuss your suitability and the project's requirements; and
3. In your application:
   • Copy and paste the title of the project from this advertisement into your application. If you don’t correctly do this your application may be rejected.
   • Submit a signed supervisory support form, a CV including contact details of 2 referees and your project research proposal.
4. Apply prior to 1 October 2026.

Full details of the application process can be found under the ' How to apply ' section of the Research Degrees website.

Following the closing date applications will be assessed within the College. Applicants should expect to receive notification of the outcome by email by the advertised outcome date.

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