Dr Martin Nicklin
MA, PhD
Clinical Medicine, School of Medicine and Population Health
Senior Lecturer
+44 114 215 9541
Full contact details
Clinical Medicine, School of Medicine and Population Health
The Medical School
Beech Hill Road
ºù«Ӱҵ
S10 2RX
- Profile
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For enquiries please contact - ClinMed-Operational@sheffield.ac.uk
I joined the University of ºù«Ӱҵ in October 1992 after studying for a PhD from 1980-1983, working on the biochemistry of cystatins (cysteine proteinase inhibitors) with Alan Barrett in Cambridge.
Then from 1984-1987 worked as a post-doctoral Damon Runyon-Walter Winchell fellow at SUNY Stony Brook with Eckard Wimmer on the replication of poliovirus (the connection being the viral cysteine proteinases) and then between 1988 and 1991 as a Junior Scientist at the Institute for Molecular Pathology in Vienna, where I worked on DNA-binding proteins Fos and Jun.
I began work at the University of ºù«Ӱҵ 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.
- Research interests
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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 and 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.
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 is dependent on specific gut colonisation by microbes.
We had long suspected a microbial trigger 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-1-like proteins that now are collectively known as IL-36, whose genes we had previously helped identify and map.
We are working to identify essential functions that have led to active IL-1-like genes being present in all sequenced mammalian genomes and yet are specific to mammals.
I have recently been engaged in producing SARS-CoV2 antigens for Clinical Seroconversion assays in collaboration with colleagues in the Department and in the NHS Trust.
Current Projects:
- 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.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- . Ann Rheum Dis, 72(11), 1860-1867.
- . Ann Rheum Dis, 71(5), 753-760.
- . Infect Immun, 80(3), 1140-1149.
- . Blood, 118(22), 5713-5714.
- . Arthritis Res Ther, 12(4), R149.
- . Arthritis Rheum, 58(11), 3461-3470.
- . J Clin Invest, 118(1), 205-216.
- . Diabetes, 54(12), 3503-3509.
- . Circulation, 111(23), 3135-3140.
- . J Invest Dermatol, 122(3), 665-669.
- . Genomics, 79(5), 718-725.
All publications
Journal articles
- . Nature Communications, 15(1).
- . iScience, 107056-107056.
- . Wellcome Open Research, 6, 220.
- . Genes and Diseases.
- . Wellcome Open Research, 6.
- . Cytokine, 68(1), 16-22.
- . Ann Rheum Dis, 72(11), 1860-1867.
- . PLoS One, 8(1), e53265.
- . Ann Rheum Dis, 71(5), 753-760.
- . Infect Immun, 80(3), 1140-1149.
- . Blood, 118(22), 5713-5714.
- . Arthritis Res Ther, 12(4), R149.
- . Arthritis Rheum, 58(11), 3461-3470.
- . J Clin Invest, 118(1), 205-216.
- . Diabetologia, 49(2), 387-393.
- . Arthritis Res Ther, 8(3), R80.
- . Diabetes, 54(12), 3503-3509.
- . Circulation, 111(23), 3135-3140.
- . J Invest Dermatol, 122(3), 665-669.
- . J Biol Chem, 277(20), 17448-17456.
- . Genomics, 79(5), 718-725.
- . Eur J Immunogenet, 29(1), 25-30.
- . Trends Immunol, 22(10), 533-536.
- . Trends Immunol, 22(10), 536-537.
- A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities.. Eur J Immunol, 30(11), 3299-3308.
- . J Exp Med, 191(2), 303-312.
- . Genomics, 57(1), 177-179.
- . Am J Hum Genet, 62(5), 1180-1188.
- . Genomics, 47(2), 325-326.
- . Genomics, 46(3), 480-482.
- An analysis of linkage disequilibrium in the interleukin-1 gene cluster.. AMERICAN JOURNAL OF HUMAN GENETICS, 61(4), A272-A272.
- . Genomics, 41(3), 370-378.
- . Brain Res Mol Brain Res, 44(2), 309-322.
- . Hum Genet, 97(6), 723-726.
- . Human Genetics, 97(6), 723-726.
- . Cytogenetic and Genome Research, 73(3), 235-239.
- Novel microsatellite markers in the interleukin-1 gene cluster. CYTOGENETICS AND CELL GENETICS, 73(4), 3-3.
- . Genomics, 19(2), 382-384.
- . Cytogenetic and Genome Research, 67(4), 215-244.
- ANALYSIS OF THE INTERLEUKIN-1 GENE-CLUSTER. CYTOGENETICS AND CELL GENETICS, 67(4), 243-243.
- Accumulated helix-destabilizing mutations in the leucine zipper of c-Fos leads to attenuation and temperature sensitivity of function.. Oncogene, 8(7), 1737-1749.
- . J Virol, 66(12), 7481-7489.
- A single site mutation in a truncated Fos protein allows it to interact with the TRE in vitro.. Oncogene, 6(1), 173-179.
- Cleavage of synthetic peptides by purified poliovirus 3C proteinase.. J Biol Chem, 264(17), 9738-9741.
- . J Virol, 62(12), 4586-4593.
- . J Virol, 62(8), 2636-2643.
- . Biochimie, 70(1), 119-130.
- . J Virol, 61(9), 2711-2718.
- . Proc Natl Acad Sci U S A, 84(12), 4002-4006.
- . Cold Spring Harbor Symposia on Quantitative Biology, 52(0), 343-352.
- . J Cell Sci Suppl, 7, 251-276.
- . Proc Natl Acad Sci U S A, 84(1), 21-25.
- . Cell, 45(5), 761-770.
- . Nature Biotechnology, 4(1), 33-42.
- . Biochim Biophys Acta, 828(2), 196-204.
- . Biochem J, 223(1), 245-253.
- . Nucleic Acids Res, 12(18), 7251-7267.
- . Biochem J, 211(1), 129-138.
- . Wellcome Open Research, 6, 220-220.
- . Cells, 10(6), 1419-1419.
Chapters
- IL-1 Receptor Antagonist-Deficient Mice In Fantuzzi G (Ed.), Cytokine Knockouts (pp. 111-134). Humana Press
- , Protein Engineering (pp. 319-337). Elsevier
Conference proceedings papers
- The Discordant Impact of IL-1 Signaling on Experimental Uveitis and Arthritis.. ARTHRITIS AND RHEUMATISM, Vol. 63(10) (pp S26-S26)
- The new IL-1 family member IL-1F8 stimulates the production of inflammatory mediators by synovial fibroblasts and articular chondrocytes. ANNALS OF THE RHEUMATIC DISEASES, Vol. 65 (pp 77-78)
- Inflammatory diseases in interleukin-1 receptor antagonist-deficient mice.. European Cytokine Network(11) (pp 200-200)
Preprints
- Teaching interests
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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 420 students over the six years that I have led the course.
The course currently has pathways in "Genetic Mechanisms", "Experimental Medicine", "Neuroscience", "Cancer", "Cardovascular" and "Microbes and Infection".
Students can chose pathways after they have been with us for 10 weeks. 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 two other modules as well as regularly supervising laboratory projects.
- Professional activities and memberships
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I am a long standing and active member of the University's Local Genetic Modification Committee and I sit on the School and Faculty Postgraduate Taught Programmes Committees.
I am Chair of the University of ºù«Ӱҵ Biosafety Sub-committee.