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Enzyme chemistry research wins 2014 UCD Conway Festival medal

PhD student, Jennifer Cleary received the 2014 UCD Conway Festival medal sponsored by Cruinn Diagnostics for research using a technique called nuclear magnetic resonance (NMR) to figure out how chymotrypsin works and how to inhibit its action.

Chymotrypsin is a digestive enzyme that breaks down proteins in the gut and falls into the category of serine proteases. Jennifer is using chymotrypsin as a model of serine proteases.

Frequently, research involves doing extensive ground work using a molecule or organism that is similar to what you actually want to investigate in humans. Scientists can then apply learnings from working with a model to human cells.

Jennifer Cleary is interested in how cancer spreads in the body. In particular, she wants to find out how the serine protease, urokinase or urokinase-type plasminogen activator (uPA) is involved in the process of tissue breakdown that can allow cancer cells to invade and spread around the body.

“The research findings that I presented at the 2014 UCD Conway Festival are a small part of my wider doctoral research project focusing in on the active site or boiler room of the chymotrypsin molecule”, said Jennifer.

There are three key amino acids or residues located in this active site that make chymotrypsin function; His-57, Ser-195, Asp-102. The NMR technique allows Jennifer to actually see the connections between residues. She identified hydrogen atoms involved in hydrogen bonds between His-57 and Ser-195 as well as between His-57 and Asp-102.

“I also used proton NMR to see what happens at the active site to these residues when I added an aldehyde inhibitor to chymotrypsin to try to stop it working”.

In order to make the serine residue reactive, the histidine residue needs to pull away a proton from the serine hydroxyl group. Histidine needs to increase its affinity for the serine proton to pull it away. This measure of affinity for the proton is the pKa.

Jennifer’s research has shown that the level of affinity or pKa does not have to be as high as previously thought to increase the reactivity of the catalytic serine by ~6000.

For the first time, using a particular software programme with the NMR technique, Jennifer was able to determine the pKa of free chymotrypsin at 250C. This is a more biologically relevant temperature than the previous studies done at 3-40C.

Jennifer Cleary works in the research group of Conway Fellow, Professor J. Paul G. Malthouse of UCD School of Biomolecular & Biomedical Science and is funded through the Irish Research Council

The 2014 UCD Conway Festival of Research & Innovation took place on September 10th and 11th in the Institute and the annual event featured the work of early career researchers as well as a programme of lectures from national and international scientists.

2014 UCD Conway Festival medal winner, Jennifer Cleary pictured with UCD President, Professor Andrew Deeks

Jennifer Cleary receives the 2014 UCD Conway Festival medal from Professor Andrew Deeks, UCD President

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