How Cells Sense Disrupted pH Gradients

Host: Mahima Swamy

Venue:  MSI Small Lecture Theatre, SLS

Abstract:

Cells require different pH concentrations for specialised functions of organelles. Low pH is maintained within the secretory and endolysosomal compartments by the action of proton pumps (V-ATPases). Viruses and bacteria frequently disturb these compartments, disrupting their pH gradients. We have discovered that the proton pump V-ATPases themselves signal to the cell when they cannot maintain appropriate pH. This leads to the deposition of proteins that are usually associated with autophagy (self-eating). We are unravelling the mechanism by which this occurs, and defining its consequences for the cell and for immune responses.

Bio:

Rupert undertook the MB/PhD Programme at Cambridge where he worked on the mechanism of somatic hypermutation in antibody genes with Michael Neuberger at the LMB. After medical training he then returned to the LMB to work in Felix Randow's lab during his training as a nephrologist. There he discovered that influenza infection targets autophagy proteins to non-autophagosomal compartments. He was awarded a MRC Clinician Scientist Fellowship to explore this further in the Division of Virology in Cambridge. In 2019 he became the first newly appointed Clinician Scientist Group Leader at the Crick (and has recently been appointed as a senior group leader). He maintains a clinical practice as a consultant at the Royal Free Hospital.