Project Reference: TRG27-IMR-JN2

Project title: Mechanobiology across organelle interaction networks

Project outline

A major outstanding challenge in cell biology is to understand how cells respond to mechanical forces, both to survive, and to make decisions. Our goal is to understand how extrinsic physical forces alter organelle interactions and the flux of biomolecules between them. Membrane contact sites (MCS) are key hubs for regulating the exchange of ions, lipids, and metabolites across organelles in a spatially and temporally coordinated manner. This exchange of material underpins the identity and function of almost every organelle. Yet a role for mechanical forces in influencing these crucial organellar communication pathways remains unknown. 

This is, in large part, because decoding complex changes across multiple organelles requires a network scale approach, and to date, technical limitations have rendered this impossible. To address this, we have developed a unique suite of imaging, biophysical and omics tools to characterize ion, lipid, and metabolite exchange at multiple contact sites on a network scale. In preliminary work, we have found that both mechanical compression and osmotic shock alter the number of contact sites formed between various interacting organelles. 

This PhD project will build on this discovery to provide critical insights into the mechanistic links between organellar interaction networks and mechanobiology. The candidate will identify novel mechanoresponsive molecules at MCS, determine the mechanisms by which mechanical information is transduced to MCS, and determine the functional consequences of organelle interaction network remodeling on cell behavior. The candidate will have access to a range of cutting-edge technologies and work as part of a highly collaborative interdisciplinary team to explore the central hypothesis that mechanical forces remodel organelle interaction networks to enable cell survival, and instruct cellular identity.

Principal Supervisor

Dr Jonathon Nixon-Abell

Email address: jjn36@cam.ac.uk

Department / Partner Institute: Cambridge Institute for Medical Research (CIMR)

Website: https://www.cimr.cam.ac.uk/staff/dr-jonathon-nixon-abell

BBSRC strategic theme

Bioscience for an integrated understanding of health