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The analysis of mitochondrial dynamics in ageing and neurodegeneration

Objective

The survival of our most active tissues, such as the brain and heart, throughout decades of a human lifespan presents an extraordinary biological challenge. Mitochondria are central to the life and death of these tissues. They provide the cellular energy required by these cells and protect them by buffering potentially lethal levels of cytoplasmic calcium, while at the same time mitochondria produce much of the molecules that cause cellular damage and contain a lethal arsenal of apoptotic cell death machinery. These organelles require exquisite maintenance processes to keep them intact and prevent potentially catastrophic disruption. Failure in mitochondrial homeostasis is strongly linked to age-related conditions such as neurodegeneration.
This subject has garnered intense interest recently with emergence that two genes linked to Parkinson's disease, PINK1 and parkin, regulate the autophagic degradation of mitochondria (mitophagy). Mitophagy is coordinated with mitochondrial dynamics, processes vital to neuronal health. While recent work has uncovered the basic mechanisms of PINK1/parkin-induced mitophagy, many questions and caveats surround the current knowledge. Most notably, all studies to date have used in vitro approaches and non-physiological manipulations. Thus, we still have a poor understanding of this process in a physiological context.
I will principally use the powerful genetic techniques of Drosophila to investigate the influence of mitochondrial dynamics on maintaining normal neuronal function and survival, and its impact on neurodegeneration, in the context of an intact animal system. I will also use molecular, cell biology and biochemical approaches in mammalian cells to complement our in vivo findings and verify their relevance to human biology. These insights will deliver a greater understanding of the role of mitochondrial dynamics in the health and dysfunction of the nervous system in a physiological context and guide therapeutic developments.

Call for proposal

ERC-2012-StG_20111109
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Host institution

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 487 963,58
Principal investigator
Alexander James Whitworth (Dr.)
Administrative Contact
Renata Schaeffer (Ms.)

Beneficiaries (3)

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 487 963,58
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
Principal investigator
Alexander James Whitworth (Dr.)
Administrative Contact
Renata Schaeffer (Ms.)
THE UNIVERSITY OF SHEFFIELD
United Kingdom
EU contribution
€ 883 955,60
Address
Firth Court Western Bank
S10 2TN Sheffield
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Claire Kennedy (Mrs.)
MEDICAL RESEARCH COUNCIL

Participation ended

United Kingdom
EU contribution
€ 114 841,82
Address
North Star Avenue Polaris House 2 Floor David Phillips Building
SN2 1FL Swindon
Activity type
Research Organisations
Administrative Contact
Irina James (Mrs.)