Cell-to-cell communication in the brain and tissue-specific phenotypes of mitochondrial disease (360G-Wellcome-219615_Z_19_Z)

£1,268,713

Mitochondria are cellular organelles primarily involved in energy production. They are considered to be key to the function of eukaryotic cells. Nevertheless, mitochondrial diseases often only present in adulthood with tissue-specific symptoms. This means that cells and tissues must have coping strategies which temporarily maintain normal function when confronted with mitochondrial dysfunction. This proposal aims to test the hypothesis that cell-type composition and metabolic interactions between different cell types renders specific tissues more or less vulnerable to mitochondrial dysfunction. The neural stem cell (NSC) niche in the developing Drosophila brain is a powerful in vivo model for the microenvironment of neurons and NSCs in our human brain. I plan to study the in vivo metabolic requirements of Drosophila NSCs (Aim 1), and the metabolic and transcriptional response of surrounding niche cells upon mitochondrial dysfunction (Aim 2). In the last part of my proposal, I will investigate how metabolic regulation of the nuclear genome provide both a nuclear sensing mechanism and a buffer to tissue-wide mitochondrial dysfunction (Aim 3). Elucidating generic mechanisms of the tissue-wide response to mitochondrial dysfunction will lead to better insight into metabolic origins of neurodegenerative diseases and cancer and has the potential to uncover novel therapeutic approaches.

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Grant Details

Amount Awarded 1268713
Applicant Surname Van Den Ameele
Approval Committee Clinical Interview Committee
Award Date 2019-12-05T00:00:00+00:00
Financial Year 2019/20
Grant Programme: Title Clinical Research Career Development Fellowship
Internal ID 219615/Z/19/Z
Lead Applicant Dr Jelle Van Den Ameele
Partnership Value 1268713
Planned Dates: End Date 2025-04-01T00:00:00+00:00
Planned Dates: Start Date 2020-04-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Patrick Chinnery