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Applications are invited for this self-funded 42 Month project within the Institute of Medical Sciences at the University of Aberdeen.
Enhancers are regions of DNA within the human genome that help maintain health by ensuring appropriate gene expression in the correct cells. Indeed, changes in the activity of enhancers, caused by changes in their DNA sequence or DNA-methylation, can alter gene expression in a way that can compromise life-long health. We have identified enhancer sequences in the human genome which are conserved in all higher vertebrates and which control health related behaviours such as anxiety, addiction and appetite. This provides us with an unrivalled opportunity to determine how genetic changes interact with environmentally controlled DNA-methylation in health and susceptibility to anxiety disorders, ethanol abuse and obesity. We have shown that environmental changes such as diet and stress can alter DNA-methylation of these enhancers in different regions of the brain. However, there are different types of DNA-methylation that seem to affect enhancers in different ways. For example, based on whole genome studies it has been hypothesised that 5-methyl-cytosine (5mC) decreases enhancer activity and that 5-hydroxy-methyl-cytosine (5hmC) increases activity.
This studentship will explore the differential effects of 5mC and 5hmC on enhancer activity using reporter assays in cell lines. In parallel the student will study how the environment affects 5mC and 5hmC deposition by methyl-transferases (DNMTs; add 5hC) and TET proteins (modify 5mC to 5hmC) in specific regions of the brain. We will initially focus on enhancer regions that control appetite, mood and addiction by regulating the expression of the brain derived growth factor (BDNF) in the brain. This will be done using cell lines as well as well mouse models in the labs of Prof MacKenzie, Dr McEwan who are both experts in the analysis of enhancer activity and Dr Gonzalez Sanchez, who is an expert in the genetics of feeding behaviour. By determining the differential roles of 5mC and 5hmC in modulating the activity of enhancers with a proven role in health-related behaviours these studies will increase our understanding the molecular basis of anxiety, addiction and appetite and how they are modulated by genetics and environment.
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Applicants to this project should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject.
We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.
Informal enquiries are encouraged, please contact Professor Alasdair MacKenzie (alasdair.mackenzie@abdn.ac.uk) for further information.
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APPLICATION PROCEDURE:
Please note: This is a self-funded opportunity.
This is a self-funding opportunity. Our typical start dates for this programme are February or October. however we may be able to accommodate start dates in other months if this is preferred.
Tuition fee rates for the 2024/2025 academic year are £4,786 pa. for Home/UK students and £27,300 pa. for international students.
Additional research costs/bench fees will also apply to this project (TBD).
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