SEMINAR - Bayliss Seminar Series: Sean Ramsey : Disturbing the balance: are signalling pathways at the mercy of an oxidised protein network? - Wed, 02 Dec 2015 12:00

Biological function in organisms and cells is maintained by signalling pathways of inter-related proteins responding to internal and external stimuli. The activities of many of the proteins involved in cell signalling are susceptible to redox changes caused by reversible oxidation of protein thiol groups during oxidative stress. Consequently, by affecting the activity of multiple proteins, oxidative stress has the potential to profoundly affect overall cell function. While it is known that elevated protein thiol oxidation is correlated with cellular dysfunction and pathology, the specific molecular mechanisms governing the interaction are poorly understood.

This project focuses on a pervasive regulator of inflammation, the NF-kB signalling pathway, which contains numerous redox-sensitive proteins. The NF-kB signalling pathway is interesting because aberrant NF-kB signalling is implicated in a wide range of pathologies including cancer, immunodeficiency disorders, arthritis, diabetes, muscular dystrophy and cardiovascular disease. Oxidative stress affects NF-kB signalling but there are contradictory reports about whether oxidative stress increases or decreases the activity of the NF-kB pathway.

I will propose a model to explain the contradiction. I will describe my plan to test this model experimentally in a cell culture model of muscle inflammation and a mouse model of dystrophy which involves inflammatory pathways.