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James Eaton

BHF CRE Cardiovascular Medicinal Chemistry graduate student

Project: Characterisation of novel Evasins

Supervisors:  Dr Akane Kawamura, Professor Shoumo Bhattacharya.

Biography

I studied for my undergraduate degree in chemistry at Cardiff University where I graduated with a first class degree and was awarded the TOCRIS Prize for Best MChem Performance and the Excellent Undergraduate Project Prize. I spent my year abroad working at the University of Toronto for Professor Patrick T. Gunning where I synthesised sensors for over active kinases. It was here that I first learned the impact chemistry can have on medicine and after this year I was fairly certain I wanted to continue in the field of medicinal chemistry after completing my studies. I returned to Cardiff for my Masters year where I was looking into the generation of cell permeable biophotonic nanoswitches under the supervision of Professor Rudolph K. Allemann. Here I worked in a more biological setting and this gave me a first taste of what being at the interface of chemistry and biology is like.

I was particularly interested in BHF CRE D.Phil course due to the interdisciplinary nature, and after having spent my third and four years of my chemistry degree seeing how chemistry and biology can tie together quite nicely I was sure the course was for me.

Having both a chemistry and a biology supervisor was appealing, as it would mean getting a good grounding in both chemistry and biology during my DPhil, ensuring that I gained an insight into all aspects of medicinal chemistry. I also felt that the taught first year would allow me to get a deeper understanding of medicinal chemistry before I undertook my research project. Having rotations and being able to work in a lab before committing to three years was also very enticing as it meant that I could make sure I was a good fit for the lab before joining.

I spent my first rotation working for Professors Darren Dixon and Charles Redwood looking into the synthesis of epigallocatechin gallate analogues for the treatment of hypertrophic cardiomyopathy. This rotation gave me a great experience of small molecule synthesis and characterisation in in vitro assays. I then spent my second rotation with Professor Shoumo Bhattacharya and Dr Akane Kawamura looking into novel multiple chemokine binding proteins (evasins) and peptides. I enjoyed this rotation so much that I decided to carry on working on this project for the next three years. I am currently recombinantly expressing a novel evasin in HEK 293 cells and characterising it in in vitro binding and cell migration assays. I am trying to dissect the molecular basis of the interaction of my evasin with its target chemokines and determine the key residues involved in binding. I am then hoping to engineer evasins with novel binding properties.  I am also aiming to discover new chemokine binding peptides through the use of an mRNA display screening technology that will be able to halt chemokine driven migration. This project should result in the generation of novel compounds that will be able to neutralise chemokine driven migration in vivo which may be useful for the treatment of disorders where pathological inflammation is implicated. 

Undergraduate Degree: Chemistry, Cardiff University

Studentship dates: 2014 intake. October 2014 - September 2018

Publications

Eaton, J. R. O., Alenazi Y, Singh K, Davies G, Geis-Asteggiante L, Kessler B, Robinson C.V., Kawamura A and Bhattacharya S. “The N-terminal domain of a tick evasin is critical for chemokine binding and neutralization and confers specific binding activity to other evasins.” The Journal of Biological Chemistry, 293, 6134-6146, April 20, 2018,

Alenazi Y, Singh K, Davies G, Eaton J.R.O., Elders P, Kawamura A and Bhattacharya S. “Genetically engineered two-warhead evasins provide a method to achieve precision targeting of disease-relevant chemokine subsets.” Sci. Rep. 2018 April 20; 8, 6333

Singh K, Davies G, Alenazi Y, Eaton J.R.O., Kawamura A, & Bhattacharya S. “Yeast surface display identifies a family of evasins from ticks with novel polyvalent CC chemokine-binding activities.” Sci. Rep. 2017 Jun 27; 7, 4267

Kraskouskaya, D., Drewry, J. A., Duodu, E., Burger, S., Eaton, J.R.O., Cisneros, G.A., Gunning, P. T. Exploring the structural determinants of selective phosphopeptide recognition using bivalent metal-coordination complexes. Med. Chem. Comm. 2013, 4, 289-292