In Situ Membrane Dynamics and Protein-Lipid Interactions in Ageing

Project: Research-related funding

Project Details

Description

Many of the major hallmarks of ageing are related to altered inter-and intra-cellular communication. Such
communications are dependent on endomembrane morphology, regulated not only by proteins that shape the
membranes but also on levels of specific lipids. The under-investigation of lipids compared to proteins, in
pathways of cellular communication, via endomembranes, has resulted in over simplifications and
misconceptions concerning the underpinning cellular signalling mechanisms. Mechanisms in signal transduction
and protein activation require targeting of proteins to membrane compartments with specific localised
morphology and dynamics dependent on their lipid composition. We hypothesise that the malfunction of cellular
compartments due to alterations in their morphology may correlate with early ageing. To determine alterations in
morphology and composition we will utilise a Cryogenic 3D spatial mass spectrometry at a high spatial
resolution of <100nm in partnership with Cryo-Electron Microscopy. This spatial resolution allows separation of
subcellular compartments, making it possible for the first time to investigate, simultaneously, membrane
morphology and composition on hydrated biological samples in situ. To examine the stated hypothesis our
interdisciplinary consortium of cell biologists, lipid biochemists, physicists and membrane biophysicists will aim
to determine the mechanistic links involved in protein-lipid interactions in endomembranes of both non-aged and
senescent cells.
Short title1,749,317
StatusNot started