Dr Martin Nicklin MA PhD
Department of Infection and Immunity
The University of Sheffield Medical School
Beech Hill Road
Tel: +44(0) 114 271 3261
Fax: +44(0) 114 271 3892
Secretary - Jean Lazenby
Tel: +44 (0)114 271 2237
I joined the University of Sheffield in October 1992 after a PhD working on the biochemistry of cystatins (cysteine proteinase inhibitors) with Alan Barrett in Cambridge from 1980-1983, a post-doctoral Damon Runyon-Walter Winchell fellowship at the State University of New York at Stony Brook, where I worked on the replication of poliovirus (the connection being the viral cysteine proteinases) from 1984-1987 with Eckard Wimmer and as a Junior Scientist at the Institute for Molecular Pathology in Vienna between 1988 and 1991 where I worked on DNA-binding proteins Fos and Jun. I began work at the University of Sheffield on mapping, discovering and searching for the functions of interleukin-1-like proteins (which we surmised would exist and would also be important!) in mouse and human. My research pathway has been from protein biochemistry through molecular biology into genetics and immunology.
Interleukin-1 is powerful pleiotropic pro-inflammatory signalling protein that has been known since the early 1980s. However, its unique biological activity has really started to be identified in the past five years. IL-1 has a single known functional receptor and another IL-1-like protein, IL-1 receptor antagonist (IL-1Ra) binds the receptor as a competitive inhibitor. In collaboration with Austin Smith, we developed IL-1Ra-deficient mice and my group an collaborators have characterised two of the chronic inflammatory phenotypes that these mice develop. Our mutations are available on BALB/c and C57BL/6 backgrounds. The strains develop different autoimmune conditions including elastic-vessel vasculitis, a psoriasis-like a skin inflammation and rheumatoid arthritis-like disease. We have recently been interested in defining a route by which IL-1 hyper reactivity (which is seen in these mice) can lead to a chronic acquired autoimmune disease that requires functional T cells. One of the most interesting findings, in collaboration with Leo Joosten and colleagues in Nijmegen, was the demonstration that early onset arthritis in the BALB/c strain under gnotobiotic conditions is dependent on specific gut colonisation, which we had long suspected on the basis of the timing and clustering of disease onset. My other research interest is in defining the critical biological function of a group of IL-1like proteins that are encoded within the genes between the IL-1 genes and IL-1 Ra. We hope to identify essential functions that have led to active IL-1-like genes being present in all sequenced mammalian genomes and yet specific to mammals.
Currently my major teaching interest is in leading, developing and teaching the MSc in Molecular Medicine. In 2010 our team (François Guesdon, Jon Shaw, Helen Marriott, Ilaria Bellantuono, Janine Kirby, Jane Shields and myself) won the Senate Award for Excellence in Collaboration in Teaching. We teach students up-to -date knowledge and technology. We also see the course as a means to develop students' skills in reading, thinking and writing like scientists. This is an intense one-year masters course, featuring six months of taught modules and five months of lab work on an individual (selected) project. The course is designed to train appropriate graduates in the reality of doing novel scientific research. We have taken on 264 students over the six years that I have led the course. The course has pathways in "Genetics", "Experimental Medicine" and "Neuroscience" which students can chose after they have been with us for 10 weeks. From 2011, we intend to introduce new pathways in "Cancer" and "Cardiovascular Science". I personally run modules entitled "From Genome to Gene Function" (MED6002) and "Genome and Sequence Analysis" (MED6005) which will also be available as Doctoral development modules, and I teach on three other modules.
I am a long standing and active member of the University's Local Genetic Modification Committee.
- Identifying the connection between IL-1Ra-deficiency and chronic inflammatory diseases.
- Finding the essential biological functions of members of the interleukin-1 family of cytokines.
- Mohanty ST, Kottam L, Gambardella A, Nicklin MJ, Coulton L, Hughes D, Wilson AG, Croucher PI, Bellantuono I. Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis. Arthritis Res Ther. 2010;12:R149.
- Koenders MI, Devesa I, Marijnissen RJ, Abdollahi-Roodsaz S, Boots AM, Walgreen B, di Padova FE, Nicklin MJ, Joosten LA, van den Berg WB. Interleukin-1 drives pathogenic Th17 cells during spontaneous arthritis in interleukin-1 receptor antagonist-deficient mice. Arthritis Rheum. 2008;58:3461-70.
- Abdollahi-Roodsaz S, Joosten LA, Koenders MI, Devesa I, Roelofs MF, Radstake TR, Heuvelmans-Jacobs M, Akira S, Nicklin MJ, Ribeiro-Dias F, van den Berg WB. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J Clin Invest. 2008;118:205-16.
- Somm E, Henrichot E, Pernin A, Juge-Aubry CE, Muzzin P, Dayer JM, Nicklin MJ, Meier CA. Decreased fat mass in interleukin-1 receptor antagonist-deficient mice: impact on adipogenesis, food intake, and energy expenditure. Diabetes. 2005;54:3503-9.
- Shepherd J, Nicklin MJ. Elastic-vessel arteritis in interleukin-1 receptor antagonist-deficient mice involves effector Th1 cells and requires interleukin-1 receptor. Circulation. 2005;111:3135-40.
- Shepherd J, Little MC, Nicklin MJ. Psoriasis-like cutaneous inflammation in mice lacking interleukin-1 receptor antagonist.J Invest Dermatol. 2004;122:665-9.
- Nicklin MJ, Barton JL, Nguyen M, FitzGerald MG, Duff GW, Kornman K. A sequence-based map of the nine genes of the human interleukin-1 cluster. Genomics. 2002;79:718-25.