Molecular basis of lipid traffic at interorganelle contact sites (360G-Wellcome-214291_Z_18_Z)

£2,267,367

One unsolved mystery of cell biology is how lipids, made in the endoplasmic reticulum, travel to other cellular membranes. This question, originally deemed solved by the discovery of vesicular traffic, was recently spotlighted by the discovery of membrane contact sites (MCS), at which lipid transport proteins (LTP) accumulate. LTPs solubilize and transport lipids between two membranes in vitro. The role of LTPs in vivo is, however, more mysterious, because lipid exchange appears to be a highly redundant process, challenging standard genetic screens. I hypothesize that redundancy allows lipid rerouting to allow proper lipid fluxes in different conditions. But this hypothesis is challenged by another limitation: no method allows to measure lipid fluxes inside the cell. I propose to develop two methods to circumvent these problems. First is a synthetic-biology approach: bacterial proteins are targeted to different organelles in a eukaryotic cell to modify lipids within these organelles and assess lipid fluxes between compartments. Second is a transposon approach that allows identifying genes that become essential when other genes are missing. Combining these approach will yield unprecedented insight into this unsolved issue. Because lipids are often dysregulated, our research will shed light on the biology of many diseases.

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Grant Details

Amount Awarded 2267367
Applicant Surname Kornmann
Approval Committee Science Interview Panel
Award Date 2018-11-27T00:00:00+00:00
Financial Year 2018/19
Grant Programme: Title Investigator Award in Science
Internal ID 214291/Z/18/Z
Lead Applicant Prof Benoit Kornmann
Partnership Value 2267367
Planned Dates: End Date 2024-06-01T00:00:00+00:00
Planned Dates: Start Date 2019-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East