Introduction

Research Groups

Select Research Group Head Prof. Sir Tom Blundell Prof. Kevin Brindle Dr Bill Broadhurst Dr Guy Brown Dr Mark Carrington Prof. Paul Dupree Prof. Gerard Evan - Head of Dept Prof. Richard Farndale Dr Giorgio Favrin Dr Jenny Gallop Dr Nick Gay Dr Andrew Grace Dr Jules Griffin Dr Brian Hendrich Dr Andrew Hesketh Dr Robin Hesketh Dr Matt Higgins Dr Florian Hollfelder Dr Hee-Jeon Hong Prof. Chris Howe Dr Marko Hyvonen Prof. Steve Jackson Dr Tony Jackson Prof. Richard Jackson Prof. Ernest Laue Prof. Peter Leadlay Dr Kathryn Lilley Dr Karen Lipkow Dr Rick Livesey Prof. Ben Luisi Dr Sarah Lummis Dr Juan Mata Dr John McCafferty Prof. Jim Metcalfe Dr Masanori Mishima Dr Eric Miska Dr Tom Monie Dr Helen Mott Dr Natasha Murzina Dr Daniel Nietlispach Dr Darerca Owen Prof. Steve Oliver Dr Luca Pellegrini Dr Markus Ralser Dr Nick Robinson Prof. George Salmond Dr Deirdre Scadden Dr José Silva Prof. Austin Smith Prof. Chris Smith Dr Nancy Standart Prof. Dame Jean Thomas Dr Aviva Tolkovsky Dr Martin Welch Dr Joyce Wong Dr Nianshu Zhang

Service & Research Support Facilities

Select by Subject or Manager DNA Sequencing Facility . . . . . Mr John Lester _______________________________ Quantitative Proteomics . . . . . Dr Kathryn Lilley _______________________________ Proteomics Core Services . . . . . Dr Mike Deery _______________________________ Protein & Nucleic Acid Chemistry . . . . . Dr Len Packman _______________________________ Metabolomics . . . . . Dr Jules Griffin _______________________________ Baculovirus Facility . . . . . Dr Darerca Owen _______________________________ Biophysics Facility . . . . . Dr Katherine Stott _______________________________ Crystallographic X-ray Facility . . . . . Dr Dima Chirgadze _______________________________ NMR spectroscopy . . . . . Dr Daniel Nietlispach _______________________________ Fermentation Facility . . . . . Dr Nianshu Zhang _______________________________ Bioinformatics & Computational Biology Services . . . . . Dr Jenny Barna _______________________________ Computer & IT Support . . . . . Dr Erik Timmers _______________________________

Past members last known active weblink

Select past member of Department Dr Stephen Bell Prof. Jonathan Blackburn Dr David Brown Dr Pak-Lee Chau Dr Hal Dixon (deceased) Dr Jessica Downs Prof. David Ellar Dr Paul Kemp Dr Simon Lovell Dr Kenji Mizuguchi Dr Massimo Paoli Prof. Richard Perham Dr Peter Reynolds Dr Philip Rubery Dr Gerry Smith Dr Margaret Sunde Prof. Jamie Vandenberg Dr Kira Weissman

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Cell Interaction Group

Research Groupings: Structural and molecular cell biology | Developmental and regenerative biology and medicine | Infection and Immunity

Communications between cells are directed through surface receptors which are activated through contact with neighbouring cells or via secreted ligands from distant cells. Recombinant antibodies provide a means to control receptor activation with potential utility in the treatment of cancer or the control of stem cell differentiation. Using phage display we have isolated and improved the affinity of several human antibodies which block receptor signalling.

• Phage display allows functional antibody fragments to be displayed on the surface of bacteriophage. Libraries of billions of such bacteriophage particles can be created and phage encoding desired antibodies can be selected from the library by a “panning” process on immobilised target antigen.

  CXCL12 is a key mediator in recruiting fibroblasts, leukocytes and endothelial cells to provide a supportive microenvironment for tumour cells. We have generated human antibodies which block the interaction of CXCL12 with its receptor CXCR4 with the potential to act at multiple levels.
• We have also made blocking antibodies to c-Met, the receptor for the cell motility factor HGF/SF. The key outcome of c-met signalling is the migration of cancer cells from the primary tumour to the local lymphatic or blood capillaries where they initiate the later stages of metastasis. C-met is therefore a key target for the therapy of invasive and metastatic cancer.
• We have generated antibodies which block ADAM17, a cancer associated metalloprotease (in collaboration with Gill Murphy, CRI Tape et al, 2011). Affinity matured variants are currently being tested in tumour xenograft models.
• Finally we have targeted Notch signalling and have generated blocking antibodies which are specific for either Notch-1 or Notch-2. We are investigating their potential in controlling stem cell differentiation.

The entire process of monoclonal antibody generation by phage display relies on simple molecular biology techniques and so is well suited for high-throughput antibody development. In a recent international pilot study we demonstrated the potential for high throughput antibody generation by generating a large panel of antibodies to 20 human SH2 domains. (Pershad et al, 2009). Furthermore we have shown that affinity maturation can be carried out in parallel on multiple antigens, resulting in a scalable method to generate antibodies with high affinity and utility. The resulting antibodies were used to identify interacting partners of the target molecule using immunoprecipitation and mass spectrometry (Anal. Biochem. In press).

Lab members
Kothai Nachiar Devi, Mike Dyson, Anna Melidoni, Tony Pope, Peter Slavny, Aneesh Karatt Vellatt

References