“Tandem repeats as hyper-variable functional modules in genomes – A systems biology approach”
Kevin Verstrepen was born in 1975 in Belgium. He obtained a Master of Science in Biological Engineering in 1999 and a PhD in Applied Biological Sciences in 2003 at the University of Leuven, Belgium. After his PhD, he moved to the U.S., where he served as a postdoctoral scientist in the laboratory of genetics pioneer Gerald Fink at the Massachusetts Institute of Technology (M.I.T.). Two years later, Verstrepen moved to Harvard University where he currently leads a team of scientists interested in fundamental and applied genetics.
The granted project is entitled: “Tandem repeats as hyper-variable functional modules in genomes – A systems biology approach”.
According to classical evolution theory, phenotypic variation originates from random mutations that are independent of selective pressure. However, recent findings suggest that the pace of evolution of different traits varies widely. Some properties are hyper-variable, while others are extremely robust and remain virtually constant over evolutionary timescales. Such differences in “evolvability” of traits opens the interesting possibility that cells may have evolved mechanisms to influence their own heritable phenotypic variability. In other words, cells might be able to induce heritable phenotypic variability when and where it is most needed. The long term goal of this research is to combine theory and experiments to investigate the mechanisms underlying genetic robustness and “evolvability”. Apart from the purely fundamental aspects, we also plan to explore practical facets, including swift evolution of pathogens. We often use the eukaryote Saccharomyces cerevisiae as a model, although we are also venturing into organisms as diverse as microbes, plants and mammals.
In this project, the focus lies on one specific topic, namely the role of tandem repeats as hyper-variable modules in genomes. Tandem repeats, also known as satellite sequences, are traditionally considered to be non-functional “junk” DNA. However, it is hard to believe that nature would foster such a wasteful system. Indeed, recent research shows that repeats function as hyper-variable modules in coding and regulatory sequences. Frequent changes in these repeat regions alter the function and/or expression of genes, allowing organisms to swiftly adapt to novel environments. Hence, repeats may be a common mechanism for organisms to generate potentially beneficial variability in certain regions of the genome, while keeping other regions stable and robust. First bioinformatics will be used to screen various model genomes and identify, categorize and analyze all tandem repeat loci. Subsequently, experimental molecular techniques will be applied in the model eukaryote Saccharomyces cerevisiae to investigate the mechanism and functional consequences of mutations in tandem repeats. The study of repeats in plants, animals and pathogenic microbes will be carried out in various collaborations.
The Odysseus jury concluded that Kevin Verstrepen is an outstanding scientist. He is creative, thoughtful, determined, and does an excellent job of sizing up the most interesting and tractable aspects of a problem. His experience in more applied as well as purely basic research gives him a considerable advantage in seeing the larger significance of a biological problem. The proposal looks very strong, especially in the experimental part: an original approach is suggested and likely to be successful; sufficient backups are considered. The project is well-structured with clearly defined intermediate goals. Kevin Verstrepen will join the internationally recognized Center of Microbial and Plant Genetics (CMPG) in the Faculty of Bioscience Engineering at the K.U.Leuven.