Development and leptin signalling in human stem cell-derived POMC neurons (360G-Wellcome-109142_Z_15_A)

£46,168

Energy homeostasis in mammals is tightly controlled by a distinct neural circuit in the hypothalamus and its dysfunction leads to obesity. Pro-opiomelanocortin (POMC) neurons are a central component of this circuit. While obesity research has been largely limited to studies in rodents in the past decades, recently published protocols now allow the in vitro generation of human POMC neurons from human pluripotent stem cells (hPSCs). This enables us to study disease-associated mechanisms directly in the human cell type relevant to obesity. In my PhD I will contribute to a thorough characterisation and optimisation of this in vitro system. I will study when human POMC neurons are born in culture, assess their responsiveness to metabolic cues that regulate their activity and test different means of enhancing this responsiveness. This in vitro characterisation of POMC neuronal activity will be complemented by transplantation studies, in which I will test whether hPSC-derived POMC neurons possess all the features of functional maturity required to reinstall energy homeostasis in obese mice. I will finally use this novel tool to study the molecular mechanisms of certain signalling pathways in human POMC neurons, which might lead to the identification of potential targets for therapeutic intervention in human obesity.

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Grant Details

Amount Awarded 46168
Applicant Surname Bartels
Approval Committee Internal Decision Panel
Award Date 2017-01-31T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title PhD Studentship (Basic)
Internal ID 109142/Z/15/A
Lead Applicant Mrs Theresa Bartels
Partnership Value 46168
Planned Dates: End Date 2019-10-01T00:00:00+00:00
Planned Dates: Start Date 2016-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England