Ubiquitin and Autophagy Networks in Health and Disease
An increasing number of distinct functions have been assigned to different types of ubiquitin modifications (mono ubiquitin, Lysine-linked and Met1-linked ubiquitin chains). In these processes Ub acts as a signalling component able to trigger molecular events in cells. We have cloned a number of Ub receptors that are able to mediate a variety of Ub functions including DNA repair, proteasomal degradation, cell survival and autophagy. We have also shown that linear ubiquitination plays a critical role in controling the NF-κB and apoptotic pathways downstream of TNF receptors. Mice and humans deficient in this pathway develop skin disorders, secondary inflammation in many organs and non-functional immune responses.

Removal of harmful protein aggregates, damaged organelles and microbes is mediated by autophagy, a process by which the cell sequesters cytosolic cargo and delivers it for degradation by the lysosome. Several experimental evidence has been provided about the molecular machinery underlying selective autophagy pathways and how their deregulation can case human diseases including neurodegeneration and cancer. Recent studies from the lab indicated a critical role for ER-phagy process in the development of senosory and autonomic neuropathy as well as the the role of TBK1 and OPTN in pathogenesis of amyotrophic lateral sclerosis (ALS).

The mechanisms controlling the interplay between phosphorylation and ubiquitination in autophagy pathways underlying the ALS pathogenesis will be discussed. By utilizing proteomic approaches with anti-GlyGLy antibodies we have mapped a global ubiquitinome of host-pathogen interactions in response to Salmonella infection. New findings on the role of Bacterial E3 ligases in regaultion of innate immunity will be further discussed.
Date: 5 February 2016, 14:00 (Friday, 3rd week, Hilary 2016)
Venue: Medical Sciences Teaching Centre, off South Parks Road OX1 3PL
Venue Details: Lecture Theatre
Speaker: Professor Ivan Dikic (Goethe University School of Medicine)
Organising department: Sir William Dunn School of Pathology
Organiser: Jo Peel (University of Oxford, Sir William Dunn School of Pathology)
Organiser contact email address: jo.peel@path.ox.ac.uk
Host: Professor Matthew Freeman (Sir William Dunn School of Pathology, University of Oxford)
Part of: Dunn School of Pathology Departmental Seminars
Booking required?: Not required
Audience: Members of the University only
Editor: Jo Peel