|Position in department||Member of Molecular and Cellular Biosciences Research Group
|Staff position||Senior Lecturer in Biochemistry
- 2011-present – Senior Lecturer, Department of Biological Sciences, University of Essex
- 2007-2011 – Lecturer, Department of Biological Sciences, University of Essex
- 2003-2007 – Postdoctoral Research Fellow, Department of Biology III, Albert-Ludwigs University of Freiburg, Freiburg im Breisgau, Germany.
- 2001-2003 - Postdoctoral Research Associate, Department of Biomolecular Sciences, UMIST (University of Manchester).
- 2000-2001 – Temporary Postdoctoral Researcher, Department of Biochemistry, University of Bristol.
- 1997-2000 - Ph.D. in Protein folding. Department of Biochemistry, University of Bristol. (Supervisor Prof. Tony Clarke).
- 1994-1997 - B.Sc. (Hons) Biochemistry. University of Bristol.
Our research interests centre on protein-protein interactions, particularly coiled coil and amyloid-based proteins, and understanding how key interactions achieve stability and specificity. We use the ‘Protein-fragment Complementation Assay’ (PCA) to screen libraries and select peptides or proteins with significant improvements in stability over wild-type interactors. Specificity of protein-protein interactions can be further improved by using a ‘Competitive And Negative Design Initiative’ (CANDI) which I have developed to maximise the energy barrier between desired and non-desired protein pairs. Work currently being undertaken includes:
- Design and screening of coiled coil based libraries, particularly for the oncogenic Jun-Fos Activator Protein-1 (AP-1) motif, to investigate the role of key residues in stability and specificity.
- Monitoring the folding of natural and designed variants of protein-protein interactions to understand how stability and specificity is manifested at the kinetic level.
- Generating peptides to bind, reverse, and prevent amyloid fibril formation, particularly for beta-amyloid, the primary factor implicated in Alzheimer’s disease (see Essex Research into Ageing).
- Development of our Wellcome Trust funded game 'Cascade' - being designed in collaboration with Fayju. Cascade seeks to increase Alzheimer's disease awareness, understanding, empathy, and to highlight the desperate need for a cure. Much more information on Cascade can be found here
We focus on the coiled coil system as it is simplistic, but highly specific, being ubiquitous and important for many biological processes; found 3-5% of the entire coding sequence it serves in transcriptional control, muscle contraction, viral infection, cell signaling, molecular chaperones, and fertilization, and is therefore the ideal test-bed on which to test specificity. In addition, many of the rules arising from interactions involving coiled coils are also applicable to other protein-protein interactions. Coiled coils are characterized by a regular repeating unit of seven amino acids (a heptad repeat) labelled a-g, with a specific pattern of hydrophobic and hydrophilic residues.
The Jun and Fos coiled coil proteins from the mammalian transcription factor activator protein-1 (AP-1) consist of a variety of cellular homologues which are expressed in different tissues, leading to increased levels of proliferation, invasion, and metastasis when upregulated. A variety of oncogenic signaling pathways converge on AP-1 which ultimately controls gene expression patterns. Accordingly, designing inhibitors to sequester specific AP-1 components is of great interest for analytical as well as therapeutic purposes. Such inhibitors are derived using a semirational library approach combined with a protein fragment complementation assay (PCA) for selecting librarymembers with highest affinity. In PCA, one half of murine dihydrofolate reductase (mDHFR) is genetically fused to the target, and the second half of mDHFR is fused to the protein library. Only library members binding to the peptide target will bring the two halves of DHFR together, render the enzyme active, and result in a bacterial colony under selective conditions. Subsequent growth competitions under selective conditions enrich the “winning” peptides, which can then be characterised.
To increase interaction specificity, we added homologous competitors to the PCA system. In this new system, library members must not only bind their target (positive design) but also bind it with higher affinity than the competitor (competition) and also evade binding to the competitor itself (negative design). Consequently, we term this a “competitive and negative design initiative” (CANDI). To demonstrate in vivo negative design, we combined CANDI with PCA selection, where non-DHFR-fragment fusions of cFos or cJun are used to compete with libraries, for an interaction with Jun and Fos target peptides.
Previous Group Members:
- Dr Tara Rao
- Dr Miao Yu
- Dr Richard Crooks
- Dr Asma Salman
|Publications||Link to publications for Jody Mason
- Invited Speaker with Fayju: Pervasive Media, The Watershed Bristol 11/2013
- Invited Speaker: RSC Chemistry and Biology of Peptides meeting, Nottingham 07/2013
- Invited Speaker: Protein-Protein Interactions: Emerging Science and Therapeutic Potential, The Royal Society, London 01/2013
- Invited Speaker: 32nd European Peptide Symposium, Athens, 09/2012.
- Invited Speaker: Prion and Alzheimer's Disease Chemical Biology Workshop, University of Sheffield, 04/2012
- Cafe Scientifique public seminar, Colchester, 04/2012.
- Invited Speaker: Parkinson's UK branch meeting, Maldon, 04/2012
- Invited Speaker: 'Research Across the Boundaries' Krebs Symposium, Sheffield, 02/2012.
- Invited Speaker: PepTalk, Coronado, San Diego, 01/2012.
- Cafe Scientifique public seminar, Beverley, 10/2011.
- Invited Seminar, University of Hull, 10/2011.
- Co-organiser Protein Society Conference at the University of Essex: "Dynamics within and between proteins", Colchester, 09/2011.
- Speaker at Parkinsons Disease Carers Day, Colchester, 05/2011.
- Invited Speaker: The Peptide Conference, Cambridge, 04/2011.
- Invited Speaker: RSC Sponsored Regional meeting on Single Molecule Spectropscopy of Biological Systems, Cambridge, 04/2011.
- Royal Society of Chemistry sponsored Talk: Protein-protein interactions at the Interface of Biology and Chemistry meeting, Norwich, 09/2010.
- Invited Seminar, Biofocus, Chesterford Research Park, 09/2010.
- Invited Speaker at Inaugural Age UK 'Research for Later Life' Meeting, Nottingham 09/2010.
- Invited Speaker 'Structure-based drug Design' meeting, San Diego, 06/2010.
- Invited Speaker 'Protein-protein Interaction meeting', Boston, 04/2010.
- Invited Seminar, University of Hull, 04/2008.
- Invited Seminar, Novartis, Horsham Research Centre, 05/2007
- Invited Seminar, Southampton University, 02/2007.
- Invited Seminar, Queen Mary University London, 01/2007.
- Invited Seminar, Leeds University Astbury Centre for Structural Molecular Biology, 05/2006.
- Invited Seminar, Roche, Basel, 09/2005.
- Invited Seminar, UMASS, Amherst Massachusetts, 03/2001
- Chemistry and Biology of Peptides, Gordon research conference, Ventura California, 02/2014
- EPSRC Chemical Biology and Biological Chemistry Theme Day, London, 12/2013
- Alzheimer's Research UK Annual Network Conference, Birmingham, 03/2012.
- Research into Ageing Annual Meeting, Nottingham 09/2011.
- Protein Society Meeting, Boston, 07/2011.
- Alzheimer's Research UK Annual Network Conference, Leeds, 03/2011.
- Protein Society Meeting 'Models of Dementia', Cambridge, 12/2010.
- Cancer Research UK Senior Fellows Meeting, manchester, 09/2010.
- Alzheimer's Research UK Annual Network Conference, Southampton, 03/2010.
- Protein Society Meeting 'Protein-protein Interactions' Sheffield, 01/2010.
- Alzheimer's Research UK Annual Network Conference, London, 03/2009.
- Protein Society Meeting, San Diego, 07/2008.
- Beatson Workshop: Tumor Invasion and Metastasis, Glasgow, 05/2006
- Protein Society Meeting, Barcelona, 04/2005.
- International Conference on Protein Sorting, Freiburg, 03/2005.
- 6th International Alzheimer's Disease / Parkinson's Disease Conference, Seville, 05/2003
- Protein Society Meeting: 'Amyloidogenic Proteins in Neurodegeneration: Therapeutic Implications'. Heriot Watt, Edinburgh, 04/2002.
- Johns Hopkins Protein Folding Meeting, Johns Hopkins University, Baltimore, 03/2000.
- EMBO Meeting 'Folding and Misfolding Inside and Outside the Cell' Oxford, 05/1998.
Editorial Board Memberships:
- 09/2014. EPSRC Overseas Travel Grant, £33,032
- 10/2012. BBSRC Industrial CASE Studentship (with Isogenica), £102,173
- 06/2012. Wellcome Trust People Award (With Gareth Bushell of www.fayju.com), £30,000
- 08/2011 Eppendorf Young Investigator Award (Runner up), £1000
- 06/2011. Royal Society Research Grant (with N Kad), £14,786
- 10/2010. Parkinson's UK PhD Studentship (with N Kad), £100,088
- 09/2010. Cancer Research UK Career Establishment Award, £388,100
- 05/2010. Wellcome Trust Project Grant, £218,000
- 01/2010. Research into Ageing New Investigator Award, £43,552
- 09/2008. Alzheimer’s Research Trust Pilot Project, £27,462
- 03/2008. Royal Society Research Grant, £12,508
- 03/2008. Essex University Departmental Research Fund, £1,938
- 11/2007. Royal Society Conference Grant, £1,220
- 10/2007. University of Essex Departmental Research Fund, £2,627
- 09/2007. New Lecturer Start-up Fund, University of Essex, £10,000
Information for Applicants:
We support applications for external or personal postdoctoral fellowships (e.g. EMBO, HFSP, Marie Curie or government funded) as well as applications from students intending to self-fund their PhD. Please contact Jody Mason for informal discussions.