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Deconvoluting Signaling Activities of Mitochondrial-derived Reactive Metabolites with Unparalleled Depth and Spatiotemporal Precision

Objective

Mitochondria-derived reactive metabolites (mt-REMs) drive context-specific immunomodulatory behaviors during metabolic reprogramming. Yet, no method can interrogate the cause-and-effects of individual mt-REMs with locale specificity and temporal resolution. Mapping mt-REM-directed signaling changes with spatiotemporal resolution would thus be transformational. I will develop a spatiotemporally-resolved in-vivo mt-REM-responsivity-mapping technology. This cross-disciplinary innovation will enable localized build-up of an individual mt-REM in one specific cell type with precise temporal, dosage, and chemotype control. For the first time, I will map cell-type-specific “first responders”, proteins attuned to react with the specific mt-REM in an otherwise unperturbed system, in a manner that alters signaling across distinct disease contexts. My ability to assimilate chemical biology, organic/medicinal chemistry, & biotechnology enables me to achieve these goals leveraging functional mechanistic models principally zebrafish, mice, and cultured primary cells. The resulting new knowledge is biomedically important: my previous work on lipid-derived metabolites supports that we can leverage this information to design drug candidates. This research project promises transformative biomedical advances and technological breakthroughs with enormous potential for unveiling reactive metabolite-guided biological mechanisms influencing cell function & disease outcomes.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-ADG

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Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 500 000,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

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No data

Beneficiaries (1)

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