Lynda Partridge

Dr Lynda Partridge

Senior Lecturer
Principal Admissions Tutor


Tel: 0114 222 4185
Email: l.partridge@sheffield.ac.uk

Research

Research Precis

Tetraspanins in health and disease

fig1Tetraspanins 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 of multi-molecular signalling platforms.

There are 33 tetraspanins in mammals and they have been implicated in fertilisation, the immune response, cancer progression and pathogen susceptibility. Our group is using specific antibodies, recombinant proteins and site-directed mutagenesis to investigate the role of tetraspanins in health and disease. We have recently demonstrated that tetraspanins are involved in controlling the formation of multinucleated giant cells (MNGCs), which are associated with chronic inflammation and certain types of infection. We are also studying tetraspanin function using a zebrafish embryo model, using morpholinos and the CRISPR/Cas9 system to knock down or knock out specific zebrafish tetraspanin genes, which show remarkable conservation with humans. After finding that they are involved in bacterial infections, we are also currently developing tetraspanin-based reagents as alternatives to antibiotics for treating infections caused by microbes such as Staphylococcus aureus (including MRSA).

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, was established in 2009, which specialises in the production of antibodies and other proteins from mammalian cell culture.

Research Keywords

Eukaryotic cell biology, immunology, tetraspanins, antibodies


I welcome applications from self-funded prospective home and international PhD students; see examples of possible projects below.

You can apply for a PhD position in MBB here.

Contact me at l.partridge@sheffield.ac.uk for further information.



Tetraspanin structure and function

The tetraspanins are a diverse, conserved family of eukaryotic membrane proteins. Their principal feature is the ability to form dynamic multi-molecular assemblies in cell membranes known as tetraspanin enriched microdomains (TEM). Tetraspanins play roles in many basic cell functions and are involved in cancer metastasis, fertilisation, the immune response and pathogen susceptibility. The project will involve investigating the biology of individual tetraspanins using novel monoclonal antibodies, model cell lines, site-directed mutagenesis, recombinant protein expression and gene knockdown techniques.

Tetraspanins and bacterial infection

The tetraspanins are a diverse, conserved family of eukaryotic membrane proteins. Their principal feature is the ability to form dynamic multi-molecular assemblies in cell membranes known as tetraspanin enriched microdomains (TEM). We have recently found that a number of bacterial species appear to “hijack” TEM as a means of adhering to and infecting mammalian cells. The project will investigate the molecular basis of this adhesion and the development of tetraspanin-based reagents for preventing bacterial infections.

Development of a novel immunotoxin

Immunotoxins represent a form of immunotherapy whereby antibodies are used to target a toxin, usually to cancer or infected host cells. However, to date, their clinical use has been limited in part due to dose-limited toxicity. We have recently indentified a novel toxin, which exhibits selectivity for rapidly dividing cells and is not taken up by most normal cells. We have shown that we can target the toxin to cancer cell lines using specific antibodies and that it inhibits their growth. The project will involve the further development and improvement of the immunotoxin.

Teaching

Level 4 Modules

MBB405 Advanced Research Topics

Level 3 Modules

MBB303 Cells as Factories
MBB311 Molecular Immunology (Module Coordinator)

Level 2 Modules

MBB263 Microbiology 2

Level 1 Modules

MBB163 Microbiology

Career History

Career History

  • 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

Honours and Distinctions

  • Fellow of the Royal Society of Biology (FRSB)
  • Chair, Royal Society of Biology, Yorkshire Branch. 








































Publications

Journal articles

Conference proceedings papers

  • Hassuna N, Monk P, Read R & Partridge L (2010) The role of tetraspanin proteins in macrophage uptake of Salmonella bacteria. IMMUNOLOGY, Vol. 131 (pp 80-80) RIS download Bibtex download
  • Partridge LJ, Varadharajan P, Hulme R & Monk P (2008) Roles for tetraspanin proteins in the fusion of human monocytes to form multinucleated giant cells. IMMUNOLOGY, Vol. 125 (pp 6-7) RIS download Bibtex download
  • Scola AM, Higginbottom A, Partridge LJ & Monk PN (2007) Different ligand-binding mechanisms used by the two C5a receptors, C5L2 and C5aR. MOLECULAR IMMUNOLOGY, Vol. 44(1-3) (pp 237-237) RIS download Bibtex download
  • Blackburn GM, Rickard JH, Cesaro-Tadic S, Lagos D, Mekhalfia A, Partridge L & Pluckthun A (2004) Passive and catalytic antibodies and drug delivery. PURE AND APPLIED CHEMISTRY, Vol. 76(5) (pp 983-989) RIS download Bibtex download
  • Wong CH, Higginbottom A, Monk P, Partridge LJ & Moore HD (2001) Inhibition of sperm-oolemma interactions by the extracellular domains of CD9 and CD81. ANDROLOGY IN THE 21ST CENTURY, SHORT COMMUNICATIONS (pp 565-572) RIS download Bibtex download
  • Yazici ZA, Behrendt M, Goodfield M, Partridge LJ & Lindsey NJ (1998) Does the CDR3 of the heavy chain determine the specificity of autoantibodies in systemic lupus erythematosus?. JOURNAL OF AUTOIMMUNITY, Vol. 11(5) (pp 477-483) RIS download Bibtex download
  • Higginbottom A, Partridge LJ & Monk PN (1996) Identification of potential ligands for CD63 from random peptide libraries. IMMUNOLOGY, Vol. 89 (pp OM117-OM117) RIS download Bibtex download
  • McCullough B, Peppa D, Monk PN, Skubitz KM & Partridge LJ (1996) A role for CD63 in signal transduction. IMMUNOLOGY, Vol. 89 (pp OM114-OM114) RIS download Bibtex download