Project:

Cellular senescence – regulatory signalling networks


Project Leader(s): Thomas von Zglinicki
Staff: Joao Passos, Carole Proctor, Glyn Nelson, Cedric Simillion, Jen Hallinan, Anil Wipat
Sponsors: BBSRC and EPSRC

Searching for the mechanisms that stabilize the senescent phenotype, Joao Passos performed kinetic series of inhibitions of candidate signal mediators informed by quantitative interactome analysis by Cedric Simillion, Jen Hallinan and Anil Wipat, leading to the discovery of a p38MAPK-centered signalling pathway that triggers mitochondrial dysfunction and thus ROS-hyperproduction in senescent cells. These ROS are necessary and, during the establishment phase of senescence, sufficient to maintain the DNA damage response and the growth arrest, as shown by Joao Passos by immunohistochemistry, Carole Proctor by stochastic modelling and Glyn Nelson by kinetic life cell imaging. To extend this into a true network analysis, Joao Passos is setting up a genome-wide siRNA screen.

Image shows senescent human fibroblasts stained for DNA damage sites (green) in the nucleus (blue), surrounded by the cytoskeletal actin network (red).

For more information contact:

Joao Passos
email: joao.passos@ncl.ac.uk

Staff

Dr Jennifer Hallinan
Lecturer

  • Telephone: +44 191 208 3866

Dr Glyn Nelson
Senior Research Associate

Dr Carole Proctor
Lecturer

Professor Thomas von Zglinicki
Professor of Cellular Gerontology

Professor Anil Wipat
Professor of Integrative Bioinformatics