Dr Peter Monk BSc PhD
Department of Infection and Immunity
The University of Sheffield
Medical School
Beech Hill Road
Sheffield S10 2RX
Office: LU115
Tel: +44 (0114 226 1312
Fax: +44 (0)114 271 3892
Email: p.monk@sheffield.ac.uk
Secretary - Jean Lazenby
Room: K129
Tel: +44 (0)114 271 2237
Email: j.lazenby@sheffield.ac.uk
Biography
I began my career in the Biochemistry Department in Sheffield in 1988 as a post-doctoral researcher, working for Professor Banks on chemoattractant signalling in monocytes, before working with Dr Birgit Helm on mast cell degranulation. In 1992, I became an independent researcher, funded by Arthritis Research UK to study the important pro-inflammatory mediator, complement fragment 5A (C5a).
In 1995, Arthritis Research UK awarded me a post-doctoral fellowship to establish my own laboratory, working on the interactions between C5a and its receptor. We were the first group to characterise the second C5a receptor, C5L2, now recognised to have important roles in inflammation and neurodegeneration. During this time, I also began work on the tetraspanin family of membrane proteins, identifying the hepatitis C virus E2 glycoprotein binding site on CD81.
I became a lecturer in the Department of Neurosciences in 2001 and was promoted to Senior Lecturer in 2007, before moving to the Department of Infection and Immunity in 2009. I became Reader in Immunology in 2013.
Research Interests:
Complement fragment receptors
The complement cascade is a series of blood proteins forming a part of the immune system that responds to infection. Complement protein fragments (C4a, C3a) produced by activation of the cascade actually cause inflammation which is normally a good thing but, when excessively produced, they exacerbate inflammatory diseases and there are no drugs currently available to prevent this. We are investigating the molecular interactions that underlie complement fragment receptor (C5aR, C3aR, C5L2) functions with the aim of developing new drugs for anti-inflammatory therapy.
NMR structure of C5a.
This receptor activation domain is the turn-helix at base of the molecule
Tetraspanins
Tetraspanins have been implicated in many of the fundamental processes involved in the development and functioning of multicellular organisms, from sponges to man. These include cell fustion, migration, secretion, adhesion and signalling. Recently, several tetraspanins have been shown to have roles in microbial infections, including hepatitis C, HIV-1 and Chlamydia. Cell ingress and egress mechanisms involving tetraspanins are exploited by these intracellular pathogens. These mechanisms can be blocked by tetraspanin-specific reagents, suggesting that tetraspnins may be valuable drug targets. However, the molecular details of tetraspanin functions have yet to be fully elucidated. We are using mammalian and zebrafish models to further our understanding of this fascinating protein family.
Dimer of CD81 EC2 domains. This domain contains the HCV binding site
Teaching Interests:
- MSc Molecular Medicine MED6006 (Allergy and Imunotherapy)
- Preclinical Medicine Laboratory-based SSC; student mentor
- BMS309 Neurobiological Basis of Brain Disease (the neuroimmunology of disease)
- MBB311 Molecular Immunology (innate immunity)
- MBB360 Third Year Undergraduate projects
- MBB460 Fourth Year Undergraduate Projects
Professional activities:
- Member of British Society for Immunology; Biochemical Society, British Inflammation Research Association.
- INSERM scientific evaluation Infection and Immunity panel member
- Co-organiser for FASEB summer research conferences on tetraspanins
- Associate editor for BMC Immunology, Frontiers of Immunology
- Industry Consultancies
Current projects:
- Analysis of the C5a receptor ligand binding site
- Control of C5a function by the second C5a receptor, C5L2
- Development of C3a receptor antagonists
- The role of CD63 in secretory lysosomes
- Tetraspanin function in monocyte giant cell formation
- Tetraspanins and intracellular pathogens
Funding
- AgeUK
- BBSRC DTG
- A*Star
Research Group
Key publications:
- Klos A, Wende E, Wareham KJ, Monk PN (2013) International Union of Pharmacology Nomenclature report: Complement Fragment Receptors. (Invited Nomenclature Report) Pharm Rev 65:500-543.
- Trikic MZ, Monk P, Roehl H, Partridge LJ (2011). Regulation of Zebrafish Hatching by Tetraspanin CD63. PLoS One 6(5): e19683. doi:10.1371/journal.pone.0019683.
- Green LR, Monk PN, Partridge LJ, Virji M, Morris P, Gorringe AR, Read RC (2011). Cooperative role for tetraspanins in adhesin-mediated attachment of bacterial species to human epithelial cells. Infection and Immunity 79(6):2241-9. Epub 2011 Apr 4.
- Partasarathy V, Martin F, Higginbottom A, Murray H, Moseley GW, Read RC, Monk PN* and Partridge LJ* (2009). Distinct roles for tetraspanins CD63 and CD9 in the formation of multinucleated giant cells. Immunology 127:237-248. (*joint principal authors). DOI: 10.1111/j.1365-2567.2008.02945.x
- Scola A-M, Johswich KO, Morgan BP, Klos A and Monk PN. (2009). The human complement fragment receptor, C5L2, is a recycling decoy receptor. Molecular Immunology 46:1149-62. DOI:10.1016/j.molimm.2008.11.001
- Ho S-H, Martin F, Higginbottom A, Partridge LJ, Varadjaran P, Recombinant extracellular domains of tetraspanin proteins are potent inhibitors of the infaction of macrophages by HIV-1. J Virol. 80:6487-6496.
- Higginbottom A, Cain SA, Woodruff TM, Proctor LM, Taylor SM, Fairlie DP & Monk PN. (2005). The effects of mutating putative activation switch residues in the human C5a receptor on the activity of a cyclic peptide antagonist. J. Biol. Chem. 280:17831-17840.
- Cain SA & Monk PN. (2002). The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des Arg74. J. Biol. Chem. 277:7165-7169.
- Higginbottom A, Quinn ER, Kuo C-C, Flint M, Wilson L, Pessi A, Nicosia A, Monk PN, McKeating JA & Levy S. (2000). Identification of residues in CD81 critical for interaction with hepatitis C virus envelope glycoprotein E2. J. Virol. 74:3642-3649.