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

Group Pages: https://www2.le.ac.uk/departments/chemistry/research/chemical_biology/hodgkinson-group-1

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.

Research within the Hodgkinson Group is focused on the synthesis of novel chemical probes and compound libraries designed to study biological processes otherwise challenging by genetic approaches. Applications include, investigating novel ligand-protein interactions, small molecule target identification, enhancing molecule membrane permeability, inhibitor design, proteasome mediated targeted degradation, and small molecule cellular imaging. Our overall goal and vision is that our validated chemical probes will have direct applications for use by the members of chemical biology and biology communities in revealing unprecedented biology, studying disease and aiding drug discovery.

There are two main areas of research in which we are currently developing new chemical probes:

Siderophore transport and antibiotic delivery: Iron is integral to many biological processes in living organisms and is essential for bacterial 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 modify bacterial spectrum of activity. Research efforts in this project involve the synthesis of novel antibiotic-siderophore conjugates to identify molecules that can demonstrate enhanced uptake and antibiotic potency, and exhibit bacterial species selectivity. We are also interesting in developing fluorescent imaging probes to monitor bacterial uptake of our conjugates. Collaborators include Professor Galina Mukamolova (Dept. of Respiratory Sciences, University of Leicester) and Dr. Martin Welch (Dept. Biochemistry, University of Cambridge).

Histone Deacetylase (HDAC) modulation: Histone deacetylases (HDACs) 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 are classified into four in classes; I, IIa, IIb, III and IV. Class I HDAC’s exist in large multi-protein complexes that play important roles in many diseases including neurological disorders, immune disorders and cancer. HDAC’s and their multi-protein complexes have been targeted for inhibitor design as anti-cancer compounds. The biological effects of particular HDAC inhibitors are hypothesised to be dependent on the specificity of HDAC inhibition. Thus, opportunities are available towards the design and synthesis of isoform and even complex selective chemical probes by differing approaches, not solely by inhibition, but also by other methods in chemical biology such as protein degradation. Collaborators include Professor John Schwabe (Dept. of Molecular and Cell Biology, University of Leicester) and Professor Shaun Cowley (Dept. Molecular and Cell Biology, University of Leicester).

Selected Publications

  • PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes, J. P. Smalley, G. E. Adams, C. J. Millard, Y. Song, J. K. S. Norris,  J. W. R. Schwabe, S. M. Cowley, J. T. Hodgkinson, Chem. Commun. 2020, 56, 4476-4479.
  • Siderophore-Antibiotic Conjugate Design - New Drugs for Bad Bugs?, K. H. Negash, J. K. S. Norris, J. T. Hodgkinson, Molecules, 2019, 24, 3314.
  • 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, 7403-7411.
  • 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, 2553-2562.
  • 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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