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EASTBIO: Study of anaesthetic neurotoxicity on neural stem cells using human brain organoids


   School of Medicine, Medical Sciences & Nutrition


Aberdeen United Kingdom Cell Biology Neuroscience Pharmacology Pharmacy Toxicology

About the Project

Supervisors:

Dr Daniel Berg - University of Aberdeen, Institute of Medical Sciences, School of Medicine -

Dr Eunchai Kang - University of Aberdeen, Institute of Medical Sciences, School of Medicine -

Professor Martin Collinson - University of Aberdeen, Institute of Medical Sciences, School of Medicine

Project Description:

Retrospective epidemiologic studies have demonstrated an association between exposure to general anaesthesia during early childhood and learning deficits or behavioural disorders. Furthermore, our previous data have shown that treating animals with anaesthetics agents during postnatal development results in abnormal neuronal development and circuitry formation in the dentate gyrus of the hippocampus, a region of the brain associated with learning and memory. The dentate gyrus is different compared to other regions of the brain in that the creation of new neurons continues throughout life in a process called adult neurogenesis. The new neurons are born from neural stem cells situated in the dentate gyrus. These new neurons play an important role in normal brain functions such as learning and memory, and aberrant adult neurogenesis has been implicated with pathological conditions including epilepsy and depression. Our recent work showed that adult neural stem cells are born during the first week after birth in mice during the time-window when exposure to anaesthesia is especially detrimental. Interestingly, previous studies have shown that adult neurogenesis is affected by anaesthesia, but little is known how exposure to anaesthesia during the critical time period of early development affects the development of the neural stem cells.

The purpose of this project is to determine how exposure to different anaesthetic agents affect the behaviour and fate potential of the neural stem cells in the developing brain.

Objective 1. To investigate the impact of anaesthesia neurotoxicity on proliferation and differentiation of dentate neural stem cells in the mouse brain in vivo.

Objective 2. To determine the effect of anaesthesia on the developing human brain using induced pluripotent stem cell-derived brain organoids. Brain region-specific organoids will be exposed to different anaesthetics and proliferation and differentiation potential of the neural stem cells will be examined.

Objective 3. To identify the molecular determinants of cell behaviour of the neural stem cells affected by anaesthetic neurotoxicity by transcriptomic analysis using RNA-sequencing.

The student will obtain knowledge of fundamental concepts of brain development including neural stem cell biology and neurogenesis. Technically, the student will learn how to culture human stem cells and brain organoids and assess neural development using immunohistochemistry, imaging, computational analyses and bioinformatics.

 

 

Application Procedure:

Please visit this page for full application information: http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts to Alison Innes at

Two references should be provided by the deadline using the EASTBIO reference form.

Please advise your referees to return the reference form to


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.
This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition (limited funding is available to provide international tuition fees). Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject.

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