Paul Heron    Ph.D.

Structure-function studies of Class I aldolase

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My thesis project involved the study of a highly complex glycolytic enzymes, fructose-1,6-bisphosphate aldolase. Aldolase is responsible for the reversible cleavage of the 6 carbon sugar into 3 carbon sugars during the process of glycolysis, the breakdown of glucose that produces the energy currency of the cell - ATP. We determined the precise reaction mechanism used by aldolase that controls the stereochemistry of carbon-carbon bond cleavage and formation. We used a structural enzymology and modeling approach to elucidate the residues involved in the stereocontrol of the reaction.

• Related Publication:

  Heron, P., Sygusch, J. 2017. Isomer Activation Controls Stereospecificity of Class I Fructose-bisphosphate Aldolases. Journal of Biological Chemistry. In press

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Development of anti-cancer agents

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Aldolase, a glycolytic enzyme, is under investigation for its potential as an anti-glycolytic target. This is noteworthy in the context of the Warburg effect, a phenotype exhibited by cancer cells involving a significant increase in the glycolytic flux. In collaboration with Dr. Casimir Blonski's group (Institut de Chimie Moléculaire et des Matériaux d'Orsay - Université de Paris), we developed and tested several high-affinity inhibitors of aldolase. We obtained high-resolution crystal structures, indicating the mode of binding of the inhibitors, which will serve as a blueprint for the design of the next generation of aldolse inhibitors. When tested in a human cancer cell line, our most potent inhibitor significantly reduced cell proliferation, validating the potential for aldolase as a viable anti-cancer target.

• Related Publication:

  Heron, P., Djilliali, R., Blonski, C., Sygusch, J. 2017. Bisphosphonate inhibitors of mammalian glycolytic aldolase. under review

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Moonlighting functions - validating the prophylactic potential for aldolase agaisnt malaria and other parasites

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FBP aldolase is also recognized for its moonlighting properties - performing more than one activity unrelated to the glycolytic function. Diverse aldolase partners are reported, including cell surface adhesins in apicomplexan parasites, in which aldolase performs a bridging function between the actomyosin complex and the cytoplasmic domain of the adhesins - an interaction that is crucial for motility and host-cell invasion. The binding mode of this interaction was investigated and our results are consistent with active site binding. The precise details of aldolase-adhesin binding has therapeutic implications, since targeting of the latter reduces host-cell invasion by parasites, including the agents responsible for malaria and toxoplasmosis.

• Related Publication:

  Heron, P. 2017. Structure-function studies of class I aldolases. Exploring novel activities: mechanism, moonlighting, and inhibition. Thesis dissertation

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Employment experience: Teaching

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From 2010 - 2016, I developed extensive oratory skills by disseminating scientific knowledge through teaching commitments for several undergraduate level courses, which included designing and conducting weekly workshops, maintaining a web-page, evaluating student progress, marking reports, attending meetings with the teaching team and contributing to the development of the teaching programme.

As a teaching assistant, I developed high proficiencies in explaining complex scientific problems, information and ideas to a range of students at different stages of understanding.

I had the opportunity to teach an undergraduate level course in structural biology to a cohort of 80 students.

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Employment experience: Writing

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In addition to the experience gained from writing articles, grant proposals and a doctoral dissertation, I have been gaining valuable experience as a medical writer for professional medical agencies, such as liV Medical Communication and Training Agency. I have written complete medical scientific reports from Advisory Board meetings in a variety of therapeutic areas, including hepatitis C, metastatic breast cancer, renal cell carcinoma, gastroenterology and schizophrenia.

• Client: Various
• Date: November 2016
• Service: Medical Writer

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Personal Interests

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I have always been a sports and outdoor enthusiast, having channeled my energy primarily into hockey, soccer, skiing, running, and hiking. I share this enthusiasm with others by organizing and leading a weekly running group for my fellow biochemists and friends. Also, I have organized and animated soccer leagues, skiing trips, and hiking trips for colleagues and friends. My passion for the outdoors has also brought me to the mountains where together with my wife, we have ascended all 48 peaks above 4000 feet in the White Mountains of New Hampshire. Our next objective is to summit the 100 highest peaks in New England. My commitment and perseverance are traits that transcend all aspects of my life.

• The passion never fades

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