Zooming in on molecules communicating with each other

Despite the tremendous successes of contemporary medicine in the last decades, there are still many diseases, such as cancer, diabetes, Parkinson’s and Alzheimer’s diseases, which are far from being not only cured or well described in terms of the characteristic symptoms but also from being understood in detail.

Sergey Samsonov

One of the most important objectives on the road to improving life quality in general is solving the actual health problems. Only through knowing the origin and comprehending the process of a pathology, can one effectively fight against it. That is why the value of the interdisciplinary research conducted by scientists ranging from physicists, chemists, biologists to medical clinical researchers focused on clarifying all the diverse aspects underlying these and other illnesses is difficult to overestimate. What is the role of molecular modelling in such big long-term and ambitious research? Why are the experiments not enough to understand the pathologies and to answer the questions on how to treat them? There are several reasons: theoretical studies are in general faster and cheaper than experiments. However, these reasons are not crucial. What really distinguishes modelling from experiments is that modelling is not only able to provide the deepest details, which are not accessible by the experiments, but also complements the experiment, explains its outcome and contributes to the rational planning of the next experiments. In this sense, modelling and experimental studies work together very effectively in an iterative manner.

In our project, we model a special class of molecules, glycosaminoglycans (GAGs), which are key participants in a number of biological processes, disruption of which could lead to severe diseases. Depending of the type of GAG, its addition to a wound can, for example, dramatically speed up the healing or, vice versa, slow it down. Although such facts have already been known for many years, the challenge is to understand why and how this happens. Why certain GAGs would work in tissue regeneration therapies and others not; why this effect is observed in some tissues but not in others. To answer these complex questions, we really need to go deep into the tissues and zoom the picture until we can observe the behaviour of individual molecules. The way in which numerous diverse molecules communicate with each other (interact) predetermines what is happening when the participants of the interactions are lacking or are in excess, and what happens if they slightly or dramatically change their properties. In our project, we in particular characterize the interactions between GAGs and other biologically relevant molecules such as proteins. This allows us to propose the mechanisms of action of these molecules and so to better understand their function. We also describe the potential consequences of the use of a novel synthetic class of GAG molecules, which undergo artificial chemical modification, in particular, phosphorylation. Our data show how attractive such class of molecules could potentially be for clinical applications in the future. Finally, because the molecules we study are not similar to other biological objects, there are no computational methodologies that are particularly developed to work with them effectively. Therefore, an essential part of our project was devoted to such development and testing approaches that could be more useful for the work with these objects we are studying. As computational tools we use, first of all, molecular dynamics, which is a technique allowing for observations on how atoms and molecules are moving and ‘communicating’ between each other in a course of time. It helps us to understand a substantial amount of the properties of the studied molecular systems. All parts of the project are tightly connected with the experimental data which we use to compare our models with. These data were obtained by our collaborators from experimental laboratories in Germany, Hungary, France, Japan, Sweden and Russia.

Our results will contribute to the better understanding of many biologically important processes where GAGs are involved, which can have a striking potential significance for the development of various therapeutic applications in the future.

How did you benefit from the POLONEZ fellowship?

I am very happy that I was able to join the MSCA Polonez programme. It allowed me to start my independent research and face principally different challenges than I used to experience as a postdoc before. Thanks to the grant, I was able to establish a research team which, in turn, assisted me in successful applications for subsequent grants. As a consequence, I extended my project team and the scope of my studies. Personally, my transfer to Poland definitely broadened my international experience, helped me to see many things in everyday life differently, and my first child was also born here in Gdańsk.

Dr hab. Sergey Samsonov graduated in Biophysics at Saint-Petersburg State Polytechnic University (2006), received two PhDs: in Structural Bioinformatics at the Dresden University of Technology (2009) and in Biochemistry at Saint-Petersburg State University (2010). In 2009 he started working on modelling glycosaminoglycans at the Dresden University of Technology as a Postdoctoral Researcher (2009-2017) and then at the University of Gdańsk as a Principal Investigator. In 2018 he was awarded habilitation at the University of Tours. At the moment, he is a Project Leader of two NCN projects (SONATA BIS and BEETHOVEN CLASSIC).