Biography and research overview
Dr Krastev is working on an independent research project to develop novel methods for studying poly(ADP-ribose)ylation, or PARsylation, in vivo, employing a set of genetic and functional assays to interrogate this process on a molecular level. He works alongside Prof Alan Ashworth’s Gene Function Team, with access to the laboratory’s expertise in cutting-edge next-generation sequencing, functional genomics and pharmacology.
Dr Krastev’s research develops and establishes the applications of in vivo biosensors to study a process of interest – PARsylation. These sensors produce a fluorescent signal only when a protein of interest is PARsylated. This allows him to ask such questions as which factors regulate the amount of PARsylation of a specific target protein or pathway, and to study how PARsylation can be modulated by genetic or pharmacological means. In addition, combining PAR biosensors with transposon-mediated genome modification provides a strategy to identify in an unbiased manner new PARsylation targets. This approach has significant advantages over previously employed in vitro purification techniques and is bound to produce a wealth of novel targets. The Gene Function team, with its expertise in transposon genomics, provides an ideal environment for the project.
PARsylation is a very promising target in anti-cancer therapy and a number of drugs that target it in vivo are being developed. However, how exactly these drugs affect the multifaceted PAR-mediated regulation of cancer cells remains largely unexplored. The pathway-specific biosensors that Dr Krastev is developing will allow scientists to dissect the precise mechanisms of PAR regulation. This will clarify which targets are relevant in anti-cancer research and will inform the rational design of drug combinations with PARsylation inhibitors.