An investigation of the mechanisms lining C5orf30 with tissue damage in RA

Around 40,000 Irish people have rheumatoid arthritis (RA), around half being adults of working age. Advances in our understanding of the how joint inflammation develops in RA have resulted in greatly improved treatments with improved outcomes for most patients, particular those with severe disease. Despite these remarkable achievements a significant proportion of patients do not have a satisfactory response and additional therapies are required. A more complete understanding of the causes of tissue damage in RA could, in the long-term, result in the identification of new treatments for patients with very aggressive forms of RA.
Using genetics we have identified a previously uncharacterised gene, C5orf30, that is associated with greater risk of developing severe damage to the joints of the hands and feet in patients with RA. We have shown that the C5orf30 protein has important anti- inflammatory and tissue protective effects in RA. We suspect that C5orf30 is underactive in many RA patients with the severe tissue damage.
Our project will investigate how genetic changes in the C5orf30 lead to differences in joint damage. To do this we will examine how the genetic variant in the C5orf30 gene influences the tissue damaging activities of a type of cell present in the joint, called a fibroblast, that is responsible for causing damage to cartilage. We will obtain fibroblasts from knee joint biopsies of RA patients and will compare how the genetic differences in C5orf30 is linked with their potential to invade and damage a laboratory models of cartilage. We will also investigate how C5orf30 works within fibroblasts by identifying proteins with which it interacts. This will lead to important new knowledge on both how C5orf30 functions and if it is a potential therapeutic target of new or established treatments.

Award Date
01 July 2016
Award Value
€256,540
Principal Investigator
Professor Gerry Wilson
Host Institution
University College Dublin
Scheme
MRCG-HRB Joint Funding Scheme