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Mechanisms and consequences of synaptic SUMOylation in health and disease

Objective

Synaptic protein SUMOylation is a completely new and exciting field of investigation. This application will investigate the roles of SUMOylation in normal and pathological synaptic transmission. The functional and pathophysiological implications for synaptic protein SUMOylation are far-reaching. SUMOylation has already been implicated in a diverse array of synaptopathies. Therefore, better understanding of the regulation and consequences of synaptic SUMOylation is of fundamental importance. The starting hypothesis is that targeted SUMOylation of pre- and postsynaptic proteins regulates synaptic transmission and can be neuroprotective through the reduction of excitotoxicity. The main proposal objectives are to: 1) Identify and functionally characterise novel synaptic SUMOylated substrates. 2) Define how SUMOylation regulates presynaptic neurotransmitter release. 3) Determine the activity-dependence of SUMO and SUMO specific protease (SENP) trafficking to synapses. 4) Elucidate the role of SUMOylation in regulating protein protein interactions at synapses. 5) Define the roles of synaptic protein SUMOylation in ischaemia. These ambitious objectives directly address important challenges at the frontier of our current knowledge of the molecular mechanisms regulating synaptic function and will open up new avenues for future basic and translational research. Novel tools and techniques will be used to test my hypotheses by identifying which synaptic proteins are SUMOylated and investigating the underlying mechanisms and downstream effects of SUMOylation in both normal neurones and in in vitro neuropathological models. My group is uniquely qualified to undertake this work because of our extensive directly relevant expertise, proven track record, library of unique tools and wealth of preliminary evidence demonstrating the viability of the experiments proposed. If funded, I believe this work will represent a novel, innovative and highly productive ERC investment.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

ERC-2008-AdG
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

UNIVERSITY OF BRISTOL
Address
Beacon House Queens Road
BS8 1QU Bristol
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 148 871
Principal investigator
Jeremy Martin Henley (Prof.)
Administrative Contact
Rachel Woodford (Ms.)

Beneficiaries (1)

UNIVERSITY OF BRISTOL
United Kingdom
EU contribution
€ 2 148 871
Address
Beacon House Queens Road
BS8 1QU Bristol
Activity type
Higher or Secondary Education Establishments
Principal investigator
Jeremy Martin Henley (Prof.)
Administrative Contact
Rachel Woodford (Ms.)