SCIENCE AT THE SHINE DOME canberra 6 - 8 may 2009

Early-career researchers

Thursday, 7 May 2009

GOTTSCHALK MEDAL

Dr Carola Vinuesa
Australian National University

Carola Vinuesa was born in Spain and obtained a medical degree at the University Autonoma of Madrid. She undertook specialist clinical training in the UK and in 2000 was awarded a PhD by the University of Birmingham. A year later she was the recipient of a Wellcome Trust International Travelling Prize Fellowship to do postdoctoral work with Professor Chris Goodnow at the John Curtin School for Medical Research at the Australian National University (ANU). Her work has led to the discovery of novel genes important for immune regulation. Since 2006 she has been leading the Humoral Immunity and Autoimmunity Group at ANU, supported by the NHMRC, the Juvenile Diabetes Research Foundation and a Viertel Senior Medical Research Fellowship. In 2008 she was awarded the Science Minister’s Prize for Life Scientist of the Year. Carola became an Australian citizen in 2007 and currently lives in Canberra with her husband and her one- and three-year old daughters.

Deciphering the genetic and cellular pathways that control antibody quality

Production of high quality antibody responses is key for protection against infection and underpins every successful vaccine to date. The quality of the antibodies produced is determined by the affinity for the pathogen they recognise, the ability to discriminate foreign invaders from our own cells and tissues, and the longevity of the response. When quality control of antibody production fails, not only we become vulnerable to potentially life-threatening infections, but antibodies that bind and destroy our own tissues may be generated. These rogue antibodies, called autoantibodies cause or contribute to different autoimmune diseases such as lupus, type 1 diabetes and rheumatoid arthritis. Over the last few years we have uncovered novel cellular and molecular pathways that control how the immune system of healthy individuals prevents autoantibody production. Screening libraries of mice harbouring numerous gene variants for signs of autoimmunity, led to the discovery of a new gene, Roquin, which prevents lupus and type 1 diabetes. We have shown that Roquin acts in T lymphocytes to repress expression of inducible co-stimulator (Icos) messenger RNA. Failure to repress this receptor breaks T cell tolerance by allowing T cell activation in the absence of infection. Our work has identified that control of the cells producing harmful autoantibodies is delegated to the, until recently obscure, subset of T cells known as T follicular helper cells. We have also shown that Roquin controls its targets via small non-coding RNAs, known as microRNAs, establishing the first link between impaired microRNA-mediated gene repression and autoimmunity.