Professor Jacek Radwan from the University of Adam Mickiewicz in Poznań received the 2020 FNP Prize in the field of life and earth sciences for demonstrating the role of evolutionary mechanism for optimizing genetic variability in shaping resistance to pathogens and tolerating own antigens.

Radwan graduated from the Faculty of Biology and Earth Sciences of the Jagiellonian University in 1987. There, he obtained a doctoral degree in 1992 and five years later a habilitation. In 2005, he received the title of professor. From 2020, he is a correspondent member of the Polish Academy of Sciences. He also is the deputy chairman of the Committee for Environmental and Evolutionary Biology of the Polish Academy of Sciences.

During his professional career, Radwan worked at the Institute of Environmental Sciences of the Jagiellonian University, the Institute of Biology of the Pedagogical University in Krakow, and the Institute of Nature Conservation of the Polish Academy of Sciences. Since 2012, he is working at the Faculty of Biology of the University of Adam Mickiewicz in Poznań.

As a holder of various scholarships, Radwan conducted research at the University of Oxford, the University of Sheffield, the Max Planck Institute for Behavioral Physiology in Germany (Humboldt Scholarship), and at the University of New Mexico in the USA (Fulbright Program).

Radwan repeatedly received awards from the rectors of the Jagiellonian University and the University of Adam Mickiewicz in Poznań. He also received a professorial grant in the Foundation for Polish Science?s (FNP) MASTER program and the award of the Minister of Science and Higher Education for scientific achievements.

Having published 121 articles, Radwan was cited over 3.5 thousand times. Two years ago his articles were cited 340 times, and then 343 times in the last year, which is an outstanding achievement in the field of evolutionary biology. He was the editor of the Polish translation of Douglas J. Futuyma?s Evolution, which is a fundamental textbook on evolutionary biology for students.

***

Professor Jacek Radwan is an evolutionary biologist. He deals with a number of significant evolutionarily issues, including sexual selection and conflict, parasite-host co-evolution, and ? especially intensively in recent years ? the evolution of the major histocompatibility complex (MHC).

Radwan?s work awarded by the FNP concerns the immune system, namely the explanation of why it is not always able to respond to an attack by pathogenic organisms.

In order to answer this question, we must observe the actions of genes of the major histocompatibility complex (MHC), which are involved in our bodies? immune response to various pathogens. These molecules present the body?s immune cells (T lymphocytes) with protein fragments from each cell. However, among these presented proteins, there are both proteins of the cell itself and proteins of pathogens. T lymphocytes are responsible for the body?s immune response, so they can recognize aggressor proteins presented in this way with the help of special receptors (TCR) and kill the infected cell or stimulate antibodies production. These special receptors are present in our bodies in millions of variants, thanks to which lymphocytes can recognize most of the proteins presented by MHC molecules.

Therefore, MHC genes play a key role in this process. Theoretically, the more MHC genes, the greater the variety of MHC proteins and the greater the organism?s chance of presenting pathogen proteins to lymphocytes and causing an immune response. However, the number of such genes in the human body is not very large, which means that sometimes our bodies are unable to defend themselves against pathogens. Why does it happen and why did our body decided on a lower MHC number?

Radwan?s team was the first to experimentally investigate the already existing hypothesis that there is an evolutionary compromise between the number of MHC genes and the number of T-cell antigen receptors (TCR), which enable the eradication of pathogens.

According to this hypothesis, a greater diversity of MHC variants would make it possible to present a greater number of antigens belonging to pathogens, but also the body?s normal proteins. Cells displaying their own normal proteins do not usually trigger an immune response because TCR-bearing lymphocytes that could bind to them and cause autoaggression are removed from the body in the early stages of immune system development. Therefore, scholars postulated that natural selection prevents the addition of further MHC gene variants to our genomes, as this would remove too many lymphocytes, thus limiting the possibility of a proper immune response against pathogens and de facto weakening our organisms.

Empirical testing of this hypothesis became possible thanks to the development of methods to identify millions of TCR variants using high-throughput DNA sequencing, in which Radwan?s team made a significant contribution. Works began in 2017 employed these methods in studies conducted on bank voles, selected as a model due to its exceptionally large inter-individual variation in the number of MHC genes in genomes. The research confirmed the assumptions about the evolutionary compromise between MHC and TCR. The studies showed that the greater variety of class I MHCs that bind proteins from viruses and other intracellular pathogens was associated with a smaller repertoire of TCR receptors. The results of the study were published in PNAS.

Moreover, the studies found that association with TCR diversity is absent from the number of MHC class II genes that bind proteins from extracellular pathogens such as many bacteria. Explaining this surprising difference will be another challenge for researchers, as will be answering the question of why males have a smaller TCR repertoire than females, which was another finding of the study.

 

 

Back