Dr James T. Hodgkinson

Dr James T Hodgkinson

Lecturer, Deputy Undergraduate Admissions Tutor

BSc (Queens University, Belfast), PhD (Cambridge), AFHEA

Tel : +44 (0)116 252 2105
Email : JTHodgkinson@le.ac.uk
Research Group : Chemical BiologyLeicester Institute of Structural and Chemical Biology

Research Interests

For current postgraduate opportunities, please click here.

For current postdoctoral opportunities, please click here.

My broad research interests involve using organic synthesis to prepare small molecules to study biological processes at a molecular level. Applications of such molecules include; mode of action(s) studies, investigating ligand-protein interactions, overcoming membrane permeability, structure activity studies and inhibitor design. The main aim is to understand how the biological processes and phenotypes under investigation can be altered and regulated with structural modifications to the small molecule.

Current research topics:

Quorum sensing: Bacterial cells within a given population can act collectively to coordinate gene expression in a cell-population density manner. This natural phenomenon termed quorum sensing (QS) is achieved by the release of small signalling molecules which can diffuse between bacterial cells and can be detected by specific receptor proteins. Many phenotypes under QS regulation play an important role in bacterial virulence and directly impact pathogenicity of bacteria to eukaryotic hosts, as well as antibiotic tolerance. My research involves the design, synthesis and biological evaluation of natural and non-natural signalling molecules for structure activity relationship studies, mode of action studies and inhibitor design. Collaborators include Dr. Martin Welch (Dept. Biochemistry, University of Cambridge), Professor David Spring (Dept. Chemistry, University of Cambridge) and Dr. Warren Galloway (Dept. Chemistry, University of Cambridge).

Siderophore mediated antibiotic delivery: Iron is integral to many biological processes in living organisms and is essential for survival. Bacteria secrete small molecules known as siderophores to chelate and scavenge iron from the surrounding environment. The siderophore-Fe(III) complex is recognized by receptor proteins on the outer membrane of bacteria and internalized into the bacterium cell by active transport. Thus, the synthesis of antibiotic-siderophore conjugates for active transport uptake into the bacteria cell has been demonstrated in instances to increase the potency of the antibiotic and also broaden bacterial spectrum of activity. Research efforts in this project involve the synthesis and identification of novel antibiotic-siderophore conjugates.

HDAC inhibition: Histone deacetylases are a family of enzymes that catalyze the removal of acetyl groups from lysine in both histone and non-histone proteins. The deacetylation of histones by HDAC’s results in structural modifications to chromatin which subsequently effects gene transcription. HDAC’s exist in large multi-protein complexes that play important roles in many diseases including neurological disorders, immune disorders and cancer. Numerous HDAC’s and their multi-protein complexes have been targeted for inhibitor design as anti-cancer compounds. HDAC’s are classified into four in classes; I, IIa, IIb, III and IV. The biological effects of particular HDAC inhibitors has been found to be dependent on the specificity of HDAC inhibition. Thus, opportunities are available for the design and synthesis of more potent, specific inhibitors. Collaborators include Professor John Schwabe (Dept. of Molecular and Cell Biology, University of Leicester) and Dr. Shaun Cowley (Dept. Molecular and Cell Biology, University of Leicester).

Selected Publications

  • The design and synthesis of an antibacterial phenothiazine–siderophore conjugate, A. Tarapdar, J. K.S. Norris, O. Sampson, G. Mukamolova,  James T. Hodgkinson*, Beilstein J. Org. Chem. 2018, 14, 2646–2650. doi:10.3762/bjoc.14.242
  • Identification of new quorum sensing autoinducer binding partners in Pseudomonas aeruginosa using photoaffinity probes, Y. R. Baker, J. T. Hodgkinson, B. I. Florea, E. Alza, W. R. J. D. Galloway, L. Grimm, S. M. Geddis, S. J. Walsh, H. S. Overkleeft, M. Welch, D. R. Spring, Chem. Sci. 2017, 8, 7403
  • A new pseudomonas quinolone signal (PQS) binding partner: MexG, J. T. Hodgkinson, J. Gross, Y.R. Baker, D.R. Spring, M. Welch, Chem. Sci. 2016, 7, 2553.
  • The synthesis of Quinolone Natural Products from Pseudonocardia sp. F. Salvaggio, J. T. Hodgkinson, L. Carro, S.M. Geddis, W.R.J.D. Galloway, M. Welch, D.R. Spring, Eur. J. Org. Chem. 2016, 3, 434-437
  • Combating multi-drug resistant bacteria: current strategies for the discovery of novel antibacterials, K. M. G. O'Connell, J. T. Hodgkinson, H. F. Sore, M. Welch, G. P. C. Salmond, D. R. Spring, Angew. Chem. Int. Ed. 2013, 52, 10706-10733.
  • Preparation of the quorum sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS) and structurally related analogues with biological activity using a microwave-assisted procedure, J. T. Hodgkinson, W. R. J. D. Galloway, M. Welch, D. R. Spring, Nature Protoc. 2012, 7, 1184-1192.
  • Design, synthesis and biological evaluation of non-natural modulators of quorum sensing in Pseudomonas aeruginosa, J. T. Hodgkinson, W. R. J. D. Galloway, M. Wright, I. K. Mati, R. L. Nicholson, M. Welch, D. R. Spring, Org. Biomol. Chem. 2012, 10, 6032-6044.
  • Microwave and flow syntheses of Pseudomonas quinolone signal (PQS) and analogues, J. T. Hodgkinson, W. R. J. D. Galloway, S. Saraf, I. R. Baxendale, S. V. Ley, M. Ladlow, M. Welch, D. R. Spring, Org. Biomol. Chem. 2011, 9, 57-61.
  • Structure-Activity Analysis of the Pseudomonas Quinolone Signal Molecule, J. T. Hodgkinson, S. D. Bowden, W. R. J. D. Galloway, D. R. Spring, M. Welch, J. Bacteriol. 2010, 192, 3833-3837.

 

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Contact Details

Department of Chemistry
University of Leicester
Leicester, LE1 7RH, UK

Email: chemistry@le.ac.uk

Tel: [+44] (0)116 252 2100

Fax: [+44] (0)116 252 3789

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