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MRC DiMeN Doctoral Training Partnership: Synthetic organoids for studying human hypothalamic development and disease


Project Description

The hypothalamus is a small area of the brain dedicated to regulating body homeostasis. Dysfunction or diseases of the hypothalamus have multiple and devastating consequences to the whole organism, including to mental health, metabolism and reproduction, creating a high demand for therapeutic options. The experimental inaccessibility of the human hypothalamus has hampered medical innovation in this area. However, the ability of stem cells to self-organise into three dimensional structures, termed organoids, has allowed recapitulation of some of the features of the hypothalamus in vitro, although, in common with organoids of other brain regions, this organisation is somewhat chaotic and unpredictable. Recent studies have provided new evidence for how stem/progenitor cells in the hypothalamus self-organise in vivo, and suggest an important role for neural adhesion molecules. The aim of this project is to test the ability of neural adhesion molecules, shown to have a role in controlling neural stem cell/precursor function, to control the temporal and spatial configuration of hypothalamic organoids, assessing the success of this recapitulation against current knowledge of early events in hypothalamic development in vivo. We will also use state-of-the-art genetic manipulation of human stem cells in vitro to test the roles of specific genes identified in these latter studies. This human-based model will provide an experimental platform for elucidating the mechanisms underpinning hypothalamus development and dysfunction.

Experimental approach will entail genetic engineering of human pluripotent stem cells (e.g. using CRISPR/Cas9), differentiation of stem cells and organoid culture.

Supervisors:
Dr Ivana Barbaric, https://www.sheffield.ac.uk/bms/research/barbaric
Professor Marysia Placzek, https://www.sheffield.ac.uk/bms/research/placzek
Professor Andrew Furley, https://www.sheffield.ac.uk/bms/research/furley

Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs
Includes:
Stipend at national UKRI standard rate
Tuition fees
Research training and support grant (RTSG)
Travel allowance
Studentships commence: 1st October 2020.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website

Good luck!

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