PhD project

Neuromodulation of intrinsic cerebrovascular rhythmicity and its importance in ischemic stroke

Call for applications for a fully financed PhD fellowship

Project description

Vasomotion is rhythmic oscillations in blood vessel diameter causing oscillations in blood flow. In the brain, oscillating nerve activity and vasomotion are synchronized. Vasomotion is suggested to be essential for matching O2 delivery to neural activity and the extent of vasomotion strongly correlates with infarct size in stroke. Vasomotion is a result of complex interaction of several intracellular pathways and extracellular modifies. We have previously shown a key role of Ca2+-activated Cl- channels for synchronization of smooth muscle leading to vasomotion in gut arteries. Vasomotion of cerebral arteries has several unique characteristics, although we know that Ca2+-activated Cl- channels are also important there.

It is an aim of this proposal to modify our model for gut artery to precisely describe the mechanisms important for generation of vasomotion in cerebral arteries. Moreover, we will assess the importance of the Ca2+-activated Cl- channel and vasomotion for infarct size in ischemic stroke.

We will induce stroke in our mouse where the Ca2+-activated Cl- channel is knocked out, correlate vasomotion patterns in vivo and in vitro with stroke outcome and compare that to wild-type mice. State-of-art brain blood flow imaging will be combined with ex vivo studies in brain slices and isolated blood vessels, where rhythmicity in the vascular wall tension will be correlated with membrane potential and intracellular Ca2+ oscillations. A library of putative Ca2+-activated Cl- channel inhibitors and activators will be tested in knockout wild type for their effect on stroke outcome

This project will provide a mechanistic understanding of cerebral vasomotion and provide tools for improvement effective cerebral blood flow in critical conditions.

Qualification

The candidate must hold master degree in natural science or medicine. Experience within cardiovascular physiology, molecular biology, neuroscience and/or transport physiology will be an advantage. The project includes 6 months of research stay in USA laboratories. The candidate should preferably have experience with

•    chronic animal experimental models and animal surgery,

•    microdissection and organ bath studies,

•    brain imaging,

•    Matlab,

•    R software,

•    expression analyses, including Western blot, immunohistochemistry and omics.

How to apply

Please submit your application via this link. Application deadline is 30 January 2023 23:59 CET. Preferred starting date is 1 April 2023.

For information about application requirements and mandatory attachments, please see our application guide

Further information

Please contact Associate Professor Vladimir Matchkov, vvm@biomed.au.dk, for further information.

All interested candidates are encouraged to apply, regardless of their personal background. Salary and terms of employment are in accordance with applicable collective agreement.  

Application guide: predefined PhD projects

Remember to consult our application guide so you are aware of our requirements for enrolment and what mandatory attachments that need to be part of your application

Aarhus University

Aarhus University is a leading public research university with global reach. The Faculty of Health offers a vibrant and informal research environment with longstanding traditions for collaboration with the Danish health care sector and with international university partners in the absolute elite.

The university main building is located in the middle of the vibrant student city of Aarhus and nearby is the Aarhus University Hospital.

Aarhus University is committed to career development. As a PhD student, you have access to dedicated supervision, career counselling and an extensive training programme.

Aarhus University strives to be an inclusive workplace that promotes equal opportunities. All interested candidates are encouraged to apply, regardless of their personal background.

A PhD is a full time time-limited position. Salary and terms of employment are in accordance with applicable collective agreement.

Before applying applicants are advised to study the rules and regulations of PhD studies at Graduate School of Health. You can also read more about doing a PhD at Aarhus University here.