The University of Sheffield
Department of Molecular Biology and Biotechnology

Immunologyim-l-p-06.jpg

Dr L J Partridge

Career History blank space

1998 - present: Senior Lecturer, Dept. Molecular Biology & Biotechnology, University of Sheffield
2009 - present: Scientific Director, Bioserv UK Ltd.
1988-1998: Lecturer, Dept. Molecular Biology & Biotechnology, University of Sheffield
1982-1988: Post-doctoral research assistant, Dept. Biochemistry, University of Sheffield
1979-1982: PhD student, Dept Immunology, University of Birmingham

Tetraspanins in health and disease.

The structure and function of tetraspanin proteins is a major interest for my research group. Tetraspanins constitute a highly conserved superfamily of transmembrane proteins, with the first member having appeared some 570 million years ago. They are widely expressed in multicellular organisms and are involved in basic cell functions such as motility, fusion and membrane trafficking. Tetraspanins are distinguished from other four-pass membrane proteins by the presence of conserved charged residues in the transmembrane domains and a defining “signature” motif in the larger of the two extracellular domains. Characteristically, they form promiscuous associations with one another and with other membrane proteins and lipids to generate a specialised type of microdomain: the tetraspanin enriched microdomain (TEM). As components of TEMs, tetraspanins maintain a network of interactions with other membrane proteins (e.g. integrins, signalling molecules), regulating the assembly multi-molecular of signalling platforms.
There are 33 tetraspanins in mammals and they have been implicated in fertilisation, the immune response, cancer progression and virus susceptibility. Our group is using specific antibodies, recombinant protein expression and site-directed mutagenesis to investigate the role of tetraspanins in health and disease. We have also recently begun exploring tetraspanin function in zebrafish, since there is remarkable conservation with humans at the gene level.

 Antibodies in research

I have also had a long-standing interest in the production and use of antibodies as tools in research and medicine. In the early 1990s, I helped establish a dedicated facility at the University for custom production of antibodies for researchers. A related spin-out company, Bioserv UK Ltd (http://www.bioservuk.com/about-bioserv-uk/index.html) was established in 2009, which specialises in the production of antibodies and other proteins from mammalian cell culture.

 

The diagram shows a giant multinucleated cell. The diagram shows a giant multinucleated cell. These cells are formed by the fusion of monocytes and are feature of chronic inflammation and reactions to foreign bodies (e.g. implants). Monocytes also fuse to form osteoclasts, cells involved in bone resorption. Our research, using recombinant tetraspanin proteins and specific anti-tetraspanin antibodies, suggests a role for tetraspanins in controlling this process.

 Recent Publications

Monk, PN Partridge, L J (2012). Tetraspanins - gateways for infection. Infectious Disorders - Drug Targets, 12 4-17
Cruz, A et al., Hautberge, H, Artymiuk, PJ, Baker, PJ, Bokori-Brown, ., Chang, C-T, Dickman, M, Essex-Lopresti, A, Harding, SV, Mahadi, NM, Marshall, LE, Mohamed, R, Nathan, S,Ngugi, SA, Ong, C, Ooi, WF, Partridge, LJ, Raih, MF, Ruzhenikov, S, Sakar-Tyson, M, Sedelnikova, SE, Smither, SJ, Tan, P, Titball, R, Wilson, SA, Rice, DW A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor eIF4A. Science 334 821-825
Trikić MZ, Monk P, Roehl H, Partridge LJ. Regulation of Zebrafish Hatching by Tetraspanin cd63. PLoS One. 2011;6(5):e19683. Epub 2011 May 19. PubMed PMID: 21625559; PubMed Central PMCID: PMC3098263.
Green LR, Monk PN, Partridge LJ, Morris P, Gorringe AR, Read RC. Cooperative role for tetraspanins in adhesin-mediated attachment of bacterial species to human epithelial cells. Infect Immun. 2011 Jun;79(6):2241-9. Epub 2011 Apr 4. PubMed PMID: 21464080.
Fanaei M, Monk PN, Partridge LJ. The role of tetraspanins in fusion. Biochem Soc Trans. 2011 Apr 1;39(2):524-8. PubMed PMID: 21428932.
Hassuna N, Monk PN, Moseley GE and Partridge LJ (2009) Strategies for targeting tetraspanin proteins: potential therapeutic applications in microbial infections. Biodrugs 23 341-359
Parthasarathy, V, Martin, F, Higginbottom, A, Murray, H, Moseley, G.W., Read, R.C, Mal, G., Hulme, R, Monk, P.N. and Partridge. L.J. (2009) Distinct roles for tetraspanins CD9, CD63 and CD81 in the formation of multinucleated giant cells. Immunology 127 237-248
Wright AJ, Higginbottom A, Philippe D, Upadhyay A, Bagby S, Read RC, Monk PN, Partridge LJ. (2007) Characterisation of receptor binding by the chemotaxis inhibitory protein of Staphylococcus aureus and the effects of the host immune response. Mol Immunol. 44 2507-25017
Scola AM, Higginbottom A, Partridge LJ, Reid RC, Woodruff T, Taylor SM, Fairlie DP, Monk PN. (2007) The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding. J Biol Chem. 282 3664-3671
Hamidpour M, Behrendt M, Griffiths B, Partridge L, Lindsey N.(2006) The isolation and characterisation of antiplatelet antibodies. Eur J Haematol. 76:331-8.
Ho SH, Martin F, Higginbottom A, Partridge LJ, Parthasarathy V, Moseley GW, Lopez P, Cheng-Mayer C, Monk PN. (2006) Recombinant extracellular domains of tetraspanin proteins are potent inhibitors of the infection of macrophages by human immunodeficiency virus type 1. J Virol. 80 6487-6496.
Martin F, Roth DM, Jans DA, Pouton CW, Partridge LJ, Monk PN, Moseley GW. (2005) Tetraspanins in viral infections: a fundamental role in viral biology? J Virol. 7910839-10851.
Muranova TA, Ruzheinikov SN, Higginbottom A, Clipson JA, Blackburn GM, Wentworth P, Datta A, Rice DW, Partridge LJ. (2004) Crystallization of a carbamatase catalytic antibody Fab fragment and its complex with a transition-state analogue. Acta Crystallogr D Biol Crystallogr 60 172-174.
Blackburn GM, Rickard JH, Cesaro-Tadic S, Lagos D, Mekhalfia A, Partridge LJ, Pluckthun A. (2004) Passive and catalytic antibodies and drug delivery. Pure and Applied Chemistry. 76 983-989
Ruzheinikov SN, Muranova TA, Sedelnikova SE, Partridge LJ, Blackburn GM, Murray IA, Kakinuma H, Takahashi-Ando N, Shimazaki K, Sun J, Nishi Y, Rice DW.(2003) High-resolution crystal structure of the Fab-fragments of a family of mouse catalytic antibodies with esterase activity.J Mol Biol. 332 423-435.
Higginbottom A, Takahashi Y, Bolling L, Coonrod SA, White JM, Partridge LJ, Monk PN. (2003) Structural requirements for the inhibitory action of the CD9 large extracellular domain in sperm/oocyte binding and fusion.Biochem Biophys Res Commun. 311 208-14.
Cesaro-Tadic, S., Lagos, D., Honegger, A., Partridge, L.J., Blackburn, G.M., Plückthun, A. (2003) Turnover-based in vitro selection and evolution of biocatalysts from a fully synthetic antibody library. Nature Biotech. 21 679-85
Moseley, G. W., Elliot, J., Wright, M.D., Partridge, L.J. and P. N. Monk (2003) CD63 Expression on Human Cancer Cell Lines. Int. J. Cancer 105 613-616
Behrendt M., Partridge L.J., Griffiths B, Goodfield M, Snaith M and Lindsey N.J (2003) The role of somatic mutation in determining the affinity of anti-DNA antibodies. Clin.Exp. Immunol. 131 182-189