blog: Introducing our IUCr 2017 travel grant winner

Congratulations to the winner of our IUCr 2017 travel grant: Nicole Bertoletti

image_IUCR_travel_grant_winner_2017Hyderabad is a modern city of 9 million people in central India. Its iconic architectural symbol, the Charminar or ‘four minarets’ draws its inspiration from the tetragonal crystal system. And fittingly, it’s against this exotic background that the 24th Congress & General Assembly of the International Union of Crystallography 2017 will be held this year. To support such an exciting event, we recently ran an IUCr 2017 travel grant competition and are excited to be able to share our interview with winner Nicole Bertoletti from Philipps-Universität Marburg in Germany:

Nicole, please tell us about your role and your research:

“I am a PhD student. I am about to finalize my dissertation in the research group of Prof. Dr. Klebe, in the department of Pharmaceutical Chemistry of the Philipps-University Marburg. During the course of my PhD, I obtained extensive theoretical and practical experience with various techniques including, but not limited to, recombinant protein expression and purification, bioinformatics as well as X-ray crystallography. The results of my work in these areas led up to now to two peer-reviewed publications in the Journal of Medicinal Chemistry. I worked on a new challenging project with the most recently identified member of the 17β-HSD protein family: the human 17β-HSD14.

This protein has so far not been thoroughly investigated in details and its physiological role remains unknown. However, experiments revealed that h17β-HSD14 is predominantly expressed in brain and due to its turnover of estradiol it may become a potential target for the treatment of neuronal diseases for which estrogens were demonstrated to have neuroprotective effects. During the last three years, I established a successful expression and purification protocol for the recombinant h17β-HSD14 protein and I elucidated the first eight crystal structures of the protein in ternary complex with its cofactor and highly potent nonsteroidal inhibitors or estrone, the product of the catalysis reaction.

Crystal structures of the protein-ligand complexes were necessary for the understanding of the inhibitors’ SAR (structure-activity relationship) and their further optimization. In fact, my studies revealed how small changes at the inhibitors’ substituents affect variations of their binding modes. In parallel, with the goal to discover new inhibitor scaffolds, we initiated a fragment-based lead discovery campaign by X-ray crystallography screening of a 96 fragment library.”

How does your research apply to the topics of discussion at the IUCr 2017 conference?

“I will actively contribute to the congress in the session M-009 “Enzymes, mechanism and drug design” with a poster presentation entitled: “X-ray Crystallography: essential tool for protein characterization and ligand optimization”. I would like to share with the crystallography community the importance of X-ray crystallography in medicinal chemistry for a rational design/optimization of ligands and its crucial role in the characterization of my target protein h17β-HSD14. We also believe that X-ray crystallographic fragment screening is a promising approach which may lead to the identification of more hits than other biophysical screening methods, especially for those ligands that have weak binding affinity, while providing essential structural information about binding modes necessary for their further optimization. In addition, my participation to the conference would allow me to discuss our findings, to present the binding mode of the crystallographic hits from our fragment screen against h17β-HSD14 and to discuss how I could use this information for the improvement of our inhibitors”

What do you hope to learn/gain from attending the conference?

“In the past years, I have already expressed my interest in the field of crystallography with my active participation of several national conferences and workshops, where I was even awarded with the MX-poster prize at the Seventh Joint BER II and BESSY II User Meeting 2015 in Berlin. The IUCr 24 meeting is the most important conference in the crystallography field with an expected attendance of over 2000 scientist from the entire world. With my scientific background, I believe that the participation at the IUCr 24 in Hyderabad would be an extraordinary chance for establish scientific connection with experts in the field with whom I would like to share the results, discuss challenges and the experience that I acquired during my work.

The IUCr 24 congress would be a superb opportunity where I could have the possibility to broaden my view on in the macromolecular crystallography field and to keep track of new developments. In fact, the conference offers an impressive scientific program that covers many areas and aspects of macromolecular crystallography and will also include presentation from industrial researchers. The participation of the IUCr meeting would not only be a great opportunity for me, but also for the entire lab that could benefit from the new knowledge that I will acquire and communicate once back home. In addition, I aspire to pursue an academic career in this field and I believe that the participation in scientific congress is crucial for this pursuit.”

Again our congratulations go out to Nicole and we look forward to welcoming both her and other crystallographers to the IUCr 2017 conference in Hyderabad where we can be found at booth number #59 & 61.

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