Dr James T Hodgkinson

Supervisor Details

Contact Details

School of Chemistry, University of Leicester

Scientific Background

Research Interests

Research group activity

My research is focused on the synthesis of novel chemical probes and their applications in studying biological processes otherwise challenging to study by genetic approaches alone. We are currently interested in developing chemical probes for class I Histone Deacetylase (HDAC) enzymes and their protein partners that exist within seven distinct class I HDAC multiprotein corepressor complexes. We are in a prime position to achieve this within the Leicester Institute of Structural and Chemical Biology and collaborate with the research groups of Professor John Schwabe and Professor Shaun Cowley in this area. Applications include using our chemical probes to investigate novel protein-protein interactions within HDAC corepressor complexes, and developing heterobifunctional molecules including proteolysis targeting chimeras (PROTACs) for the targeted degradation of class I HDACs and associated partners via the proteasome. Our goal is that our validated chemical probes will reveal new knowledge and biology of the protein of study and aid the discovery of new therapeutics to treat diseases such as cancer. Importantly, we also want our chemical probes to have applications for others in the research community.

Scientific Inspiration

Alexander Fleming – the discovery of the small-molecule penicillin from mould changed the world and medicine as we know it.

Research Groups

Chemical Probe Synthesis and Chemical Biology

Supervision Style

In three words or phrases: Laid-back day-day, outcome-oriented over set goals, supportive, goal-driven, student-centred, organised, collaborative, guiding, teaching, understanding, inclusive.

Provision of Training

You will be trained by both myself and a PhD student or PDRA at the beginning of the project. We will make sure the first experiments and goals are well defined and planned for high chances of success. As time progresses I would expect more independence and setting your own research goals for the project, however you will still receive close supervision and guidance as I have an open-door policy. It’s important to talk about science, even informally, and regularly.

Progression Monitoring and Management

I like to be kept up to date, and will expect to see discuss data generation and results on a biweekly basis. I am also here for advice and guidance to help you reach the goals you set for yourself at anytime.

Communication

I am happy to discuss any issues that are impacting your ability to fulfil your potential or my/our expectations.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per fortnight

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per fortnight

The meetings will be face to face and I am usually contactable for an instant response (if required) on every working day.

Working Pattern

Work in my lab requires being present on site (be it in a laboratory or at a field site) during the core hours (or a subset if working part time).

Notice Period for Feedback

I need at least 2 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Primary supervisor for:

The synthesis and evaluation of novel proximity-inducing molecules to modulate post-translational modifications

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

The synthesis and evaluation of novel proximity-inducing molecules to modulate post-translational modifications

Secondary Supervisor(s): Professor Shaun Cowley

University of Registration: University of Leicester

BBSRC Research Themes: Integrated Understanding of Health (Ageing, Pharmaceuticals)

Project Outline

"Proteins are dynamic molecules, constantly regulated by post-translational modifications (PTMs)â€”chemical changes that fine-tune their function, stability, and interactions. Dysregulation of PTMs has been linked to a wide range of diseases, including cancer, neurodegeneration, and even ageing itself [1]. Yet, studying the biological role of specific PTMs on individual proteins remains a major challenge due to the vast diversity of proteins and modifications.

This interdisciplinary PhD project offers a novel chemical biology approach to address this challenge. You will design and synthesise proximity-inducing molecules -custom-built compounds that bring a protein of interest into close contact with a PTM-modifying enzyme [2]. These molecules consist of two protein-binding ligands connected by a linker, enabling selective PTM modulation in living cells. This strategy allows researchers to study PTMs in real time, with high specificity and temporal control.

You will gain hands-on experience in:

Organic synthesis of bifunctional molecules with tunable linkers

Analytical chemistry (NMR, MS, HPLC) for compound characterisation

Cell biology techniques including immunoprecipitation, western blotting, and biological mass spectrometry

This project is ideal for students passionate about chemical biology, synthetic chemistry, and molecular mechanisms. You'll join a collaborative research environment and contribute to a transformative platform for probing protein regulation with precision. The studentship should prepare you for a future career in synthesis, chemical biology and the life sciences.

[1]. 1. Q. Zhong, X. Xiao, Y. Qiu, Z. Xu, C. Chen, B. Chong, X. Zhao, S. Hai, S. Li, Z. An, L Dai, 2023, Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications. MedComm, 4(3), p.e261

[2] Liu, X. and Ciulli, A., 2023. Proximity-Based Modalities for Biology and Medicine. ACS Cent. Sci. 9, 1269-1284

Co-supervisor on projects with: Dr Kogularamanan Suntharalingam, Dr Robert Britton