Department of Biology & Biochemistry

Jody Mason

Senior Lecturer

4 South 1.44

Tel: +44 (0) 1225 386867

Email: j.mason@bath.ac.uk

 

Dr Jody Mason

Profile

My group focuses on two key disease areas;

  • switching off a cancer-causing transcriptional protein (Activator Protein-1) thereby enabling a greater understanding of how this oncogenic protein functions in cancer and
  • blocking aggregation of β-amyloid and α-synuclein peptides associated with the generation of neurotoxic agents in Alzheimer's and Parkinson’s diseases.

To antagonise these major players in chronic disease and ageing we employ semi-rational design using Protein-fragment Complementation Assays (PCA). In PCA key regions responsible for mediating binding between proteins are scrambled and library screening and selection is performed inside cells to remove insoluble, protease susceptible and non-specific library members. Target-specificity is aided by a Competitive And Negative Design Initiative (CANDI), while Iterations of Truncation, Randomisation and Selection (TRaSe) help to identify the smallest functional units required for effective binding. Sequences are refined using non-peptidic constraints such as sequence retro-inversal, non-natural amino acid substitution, and introduction of structure-stabilizing constraints, with the aim of generating molecules capable of modulating disease while circumventing many traditional drug development barriers.

Publications 

Baxter, D., Perry, S., Hill, T., Kok, W., Zaccai, N., Brady, L., Fairlie, D. and Mason, J., 2017. Forthcoming. Downsizing protooncogene cFos to short helix-constrained peptides that bind Jun. ACS Chemical Biology

McDowall, J. S., Ntai, I., Hake, J., Whitley, P. R., Mason, J. M., Pudney, C. R. and Brown, D. R., 2017. Steady-State Kinetics of α-Synuclein Ferrireductase Activity Identifies the Catalytically Competent Species. Biochemistry, 56 (19), 2497–2505.

Crooks, R., Lathbridge, A., Panek, A. and Mason, J., 2017. Computational prediction and design to create iteratively larger heterospecific coiled coil sets. Biochemistry, 56 (11), pp. 1573-1584.

Baxter, D., Ullman, C. G., Frigotto, L. and Mason, J. M., 2017. Forthcoming. Exploiting Overlapping Advantages of in vitro and in cellulo Selection Systems to Isolate a Novel High-affinity cJun Antagonist:Combining In vitro and In cellulo library screening. ACS Chemical Biology

Shepperd, N. E., Harrison, R. S., Ruiz-Gomez, G., Abbenante, G., Mason, J. M. and Fairlie, D. P., 2016. Downsizing the BAD BH3 peptide to small constrained alpha-helices with improved ligand efficiency. Organic & Biomolecular Chemistry, 14 (46), pp. 10939-10945.

Crooks, R. O., Baxter, D., Panek, A. S., Lubben, A. T. and Mason, J. M., 2016. Deriving heterospecific self-assembling protein-protein interactions using a computational interactome screen. Journal of Molecular Biology, 428 (2, Part A), pp. 385-398.

Cheruvara, H., Allen-Baume, V. L., Kad, N. M. and Mason, J. M., 2015. Intracellular screening of a peptide library to derive a potent peptide inhibitor of α-synuclein aggregation. Journal of Biological Chemistry, 290, pp. 7426-7435.

Mason, J. M. and Fairlie, D. P., 2015. Toward peptide-based inhibitors as therapies for Parkinson's disease. Future Medicinal Chemistry, 7 (16), pp. 2103-2105.

Baxter, D., Ullman, C. and Mason, J., 2014. Library construction, selection and modification strategies to generate therapeutic peptide-based modulators of protein-protein interactions. Future Medicinal Chemistry, 6 (18), p. 2073.

Acerra, N., Kad, N. M., Cheruvara, H. and Mason, J. M., 2014. Intracellular selection of peptide inhibitors that target disulphide-bridged Aβ42 oligomers. Protein Science, 23 (9), pp. 1262-1274.

Acerra, N., Kad, N. M., Griffith, D. A., Ott, S., Crowther, D. C. and Mason, J. M., 2014. Retro-inversal of intracellular selected β-amyloid-interacting peptides:Implications for a novel Alzheimer’s disease treatment. Biochemistry, 53 (13), pp. 2101-2111.

Acerra, N., Kad, N. M. and Mason, J. M., 2013. Combining intracellular selection with protein-fragment complementation to derive Aβ interacting peptides. Protein Engineering Design and Selection, 26 (7), pp. 463-470.

Rao, T., Ruiz-Gómez, G., Hill, T. A., Hoang, H. N., Fairlie, D. P. and Mason, J. M., 2013. Truncated and helix-constrained peptides with high affinity and specificity for the cFos coiled-coil of AP-1. PLoS ONE, 8 (3), e59415.

Mason, J. M., Bendall, D. S., Howe, C. J. and Worrall, J. A. R., 2012. The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c6A. Biochimica Et Biophysica Acta-Proteins and Proteomics, 1824 (2), pp. 311-318.

Crooks, R. O., Rao, T. and Mason, J. M., 2011. Truncation, randomization, and selection:Generation of a reduced length c-Jun antagonist that retains high interaction stability. Journal of Biological Chemistry, 286 (34), pp. 29470-29479.

Worrall, J. A. R. and Mason, J. M., 2011. Thermodynamic analysis of Jun-Fos coiled coil peptide antagonists. FEBS Journal, 278 (4), pp. 663-672.

Mason, J. M., 2010. Design and development of peptides and peptide mimetics as antagonists for therapeutic intervention. Future Medicinal Chemistry, 2 (12), pp. 1813-1822.

Mason, J. M., 2009. Electrostatic contacts in the activator protein-1 coiled coil enhance stability predominantly by decreasing the unfolding rate. FEBS Journal, 276 (24), pp. 7305-7318.

Mason, J. M., Hagemann, U. B. and Arndt, K. M., 2009. Role of hydrophobic and electrostatic interactions in coiled coil stability and specificity. Biochemistry, 48 (43), pp. 10380-10388.

Mason, J. M., Muller, K. M. and Arndt, K. M., 2009. Peptides tailored to interfere with protein interaction and function. Chimica Oggi-Chemistry Today, 27 (2), pp. 47-50.

Mason, J. M., Müller, K. M. and Arndt, K. M., 2008. iPEP:Peptides designed and selected for interfering with protein interaction and function. Biochemical Society Transactions, 36 (6), pp. 1442-1447.

Hagemann, U. B., Mason, J. M., Müller, K. M. and Arndt, K. M., 2008. Selectional and mutational scope of peptides sequestering the Jun–Fos coiled-coil domain. Journal of Molecular Biology, 381 (1), pp. 73-88.

Willemsen, T., Hagemann, U. B., Jouaux, E. J., Stebel, S. C., Mason, J. M., Muller, K. M. and Arndt, K. M., 2008. Protein engineering. In: Walker, J. M. and Rapley, R., eds. Molecular Biomethods Handbook, 2nd ed. Totowa, U. S. A.: Humana Press, pp. 587-631.

This list was generated on Sat Aug 19 17:19:38 2017 IST.

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