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Grooving their way to new horizons in protein chemistry

***Speaker update alert: The talk of Prof. Wells has been cancelled. New speaker, Dr Raphaël Rodriguez, Institut Curie, FR***

The session of the 2020 International Symposium on Chemical Biology is dubbed, “Shaking the Firmaments of Biology”. As this session is to be given by Profs. Dorothee Kern (Brandeis University) and Jim Wells (University of California San Fransisco), this title is apt, seeing as both these scientists have made fundamental and highly applicable advances to our understanding of proteins, which are the bedrock and workhorses of cells, and hence life.

These two luminaries are going to regale us with their science, that spans problems that have been framed over the “recent” billions of years of our universe, but remain hugely relevant and topical today, so I thought perhaps we should first consider what the word “protein” really means.

The word “protein” bears resemblance to a word that describes the properties of amino acid polymers as we know them today very accurately, “protean,” the property of being able to change shape. However, as so often in science, in spite of the similarity, there is no connection between these two words. Protein is, in fact, derived from the Ancient Greek πρωτεῑον, meaning “the first”. This word was chosen because at the time of being coined, it was believed that proteins were responsible for the “spark of life”. Although erroneous, this root has stuck in many European languages. Perhaps just as intriguingly, the other principal European root for the word describing amino acid polymers derives from egg white (for instance the German “eiweiß”). Eiweiß and similarly-derived words catch the protean flavor of proteins as the word reflects how by increasing temperature, the clear colorless viscous liquid surrounding the egg yolk, transforms to a harder white gelatinous solid, “egg white,” even though the primary sequence does not change. So, even if the crown of being “the first” slipped a long time ago, the appearance of words like egg white (eiweiß) in the European lexicon should remind us that, even way back when, it was the versatile, or protean, nature of proteins that made them stand out. Our pioneers in this section have focused their careers on understanding this versatility and using it to our advantage to understand mechanism, and develop diagnostics or therapeutics.

Prof. Kern has spent her career breaking down the dynamical changes, or “dance choreography” that proteins undergo during catalysis, binding, or other important processes. Prof. Kern was not content with the snapshots offered by protein crystal structures that started to flood into the literature during the 1990s. It was her dream to understand all the full repertoire of moves that each specific protein is capable of, and how each box step, or “free spin” come together to usher a specific biological event. Thus, just like the great pioneer of photography, Eadweard Muybridge, who was the first to prove that during a canter, all four of the horse’s feet are off the ground at the same time, Prof. Kern was drawn to methods that can spy on proteins motions in real time. To deconstruct all the steps in each protein’s routine Prof. Kern has used cutting edge techniques such as nuclear magnetic resonance, fluorescence resonance energy transfer, and married those techniques with traditional enzyme kinetics and phylogeny. Her work has been honored with numerous awards, including the Pfizer Award in Enzyme Chemistry and the Dayhoff Award.

Prof. Wells has realized that to tackle some of the worlds most devastating diseases, you only need to scratch the surface. This is because during diseases such as cancer, the way the cell processes and responds to outside information is modified. Much of this varied responsivity is manifest(ed) through changes in/remodeling of cell surface proteins. Interfering with these new networks offers diagnostic and therapeutic interventions. This quest has led Prof. Wells to investigate regulation of protein-protein interactions, a property long-considered to be unshakable and hence undruggable, and to engineer new methods to probe signaling pathways amongst a host of others. Prof. Wells is undeniably a scholar and has published many excellent reviews and perspectives in addition to his outstanding research output. He is a member of the National Academy of Sciences, and has been awarded the Pfizer Award for achievements in enzyme chemistry.


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