Trinity Immunologist Awarded Prestigious Medical Grant
Posted on: 08 March 2012
Professor of Immunology, Professor Andrew Bowie, of Trinity’s School of Biochemistry and Immunology, has been awarded a National Institutes of Health (NIH) grant along with co-investigator Dr Katherine Fitzgerald to support their research on ‘DNA sensors and associated signaling pathways in the innate immune response’. The research project, which will receive a total of $1.25m over five years, was ranked in the top 1% of grants submitted to the National Institute of Allergy and Infectious Diseases (NIAID) and was based on work previously funded by Science Foundation Ireland.
In order for the immune system to function properly and fight pathogens, it must first be able to detect the presence of bacteria and viruses in the body. To do this, the body uses immune sensors called Pattern Recognition Receptors (PRRs), that survey the inside and outside of cells for the presence of bacteria and viruses. However, our understanding of how PRRs signal to turn on the immune response is still incomplete. Once a PRR detects a pathogen an alarm response is triggered in the body which involves the production of proteins called interferons and cytokine. These proteins shut down infected and surrounding cells in order to contain the virus. Trinity researchers have made two significant discoveries relating to immune sensors – in 2008 Trinity researchers discovered a function for the molecule ‘DDX3’ as a signaling protein for PRRs, and in 2010 researchers discovered a new PRR called ‘IFI16’ that detects the presence of viruses inside cells by binding to viral DNA.
Human cells (left panel) stained to show IFI16 detecting pathogen DNA (red arrow, right panel). Image generated by Marcin Baran.
As well as the vital positive role of PRRs in sensing pathogens, during autoimmune diseases PRRs have a negative role in that they are turned on inappropriately. In the absence of pathogens an immune response leads to the development of autoimmune and chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and inflammatory bowel disease. Understanding how PRRs work is vital for health and disease and further research will enable the design of drugs to enhance immunity during infection or increase the potency of vaccines. Research into PRRs could also pave the way for the design of drugs that could inhibit ‘IFI16’ and ‘DDX3’, which may be useful in the treatment of autoimmune diseases.
Commenting on the significance of the award Professor Bowie said: “The grant will allow us to gain further insight into how DDX3 and IFI16 detect pathogens to mount an immune response, and to explore their importance in host defence against a range of bacteria and viruses. This should lead to breakthroughs in the treatment of infectious disease and of autoimmunity. We were delighted that the project scored so highly in the fiercely competitive NIH grants system, which is an endorsement of the investment by SFI in supporting basic research in Ireland, leading to us being able to leverage significant international funding.”
NIH, based in the US, is the largest source of funding for medical research in the world while NIAID, and institute of NIH, conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic and allergic diseases.