Valentin Borshchevskiy wins the Young Scientist Award at the ESRF’s User Meeting 2021

09-02-2021

Valentin Borshchevskiy, researcher at the Moscow Institute of Physics and Technology, has been awarded the Young Scientist Award by the ESRF User Organisation for his outstanding contribution to the understanding of structure-based functional properties of membrane proteins. A regular user at the ESRF since 2005, he initiated the Beamtime Allocation Group (BAG) for Russia five years ago. He was awarded the prize at the 2021 ESRF’s User Meeting, which is taking place online this week, with 900 scientists assisting from 40 different countries.

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About a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs. They are involved in essential cellular and physiological processes, including signal and energy transduction, transport of ions and nutrients or catalysis of chemical reactions.

Borshchevskiy focuses on membrane proteins and started to use the structural biology beamlines at the ESRF already as a master student back in 2005. During PhD years at the Institut de Biologie Structural, in Grenoble, he became a regular user. After his PhD on membrane proteins, he went back to his native Russia to contribute to creation of a lab for protein crystallography from scratch, which has now become a research centre comprising 8 labs. Throughout his career, his visits to the ESRF have never stopped: “The ESRF is absolutely crucial for my research, without the ESRF I wouldn’t be where I am now”, explains Borshchevskiy, who has authored 55 papers, including two in Science. “For this, I am really pleased to be awarded the YSA”, he adds.

Borshchevskiy divides his time in two different projects within membrane proteins: G protein-coupled receptors (GPCRs) and retinal proteins. Both of these kind of proteins consist of 7 transmembrane helixes and both are very complicated to crystallise.

Retinal proteins are investigated for optogenetic applications (a method to influence cells with the help of light). These proteins can absorb light, and they can either transport a signal through the membrane, like for example in the eyes, or they can transport ions. Borshchevskiy explains how he studies them and the role of the ESRF: “We want to know how they work and for that we need to find out how they are organized. So we crystallise them and take them to the ESRF’s structural biology beamlines. At the ESRF we collect very valuable data on the basic state but also when they are activated by light. Once we have all this information, we can mutate them and change their properties, efficiency, etc.” The medical applications of these proteins are potentially huge and are already being investigated to restore the ear function (as alternative to cochlear implants), to restore vision or for deep brain stimulation in neurodegenerative diseases.

GPCRs have a similar topology as retinal proteins but their function is completely different. These are probably the most important proteins in humans because most of the receptors in the body are GPCRs. There are over 800 of them and over 30% of all drugs prescribed today act on GPCRs.

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Valentin Borshchevskiy in his lab in Moscow. Credits: MIPT press office.

Borshchevskiy and his team have investigated two GPCRs which are normally studied for the development of asthma drugs. After finding their structure thanks to their experiments at the ESRF, they realised that when one of these proteins presents a mutation, they are directly responsible for causing a rare and fatal melanoma. The team has found how to inhibit this protein and they are now working for the potential development of treatments.

“I’ve come a long way with both projects, which I started when not many people were working on them and now we can see how they can actually lead to medical applications”, explains Borshchevskiy. “Throughout, X-ray crystallography has been my method of choice and the ESRF is an essential part of my research”, he concludes.  

Text by Montserrat Capellas Espuny

Top image: Valentin Borshchevskiy. Credits: MIPT press office.