Opis projektu
Odkrywanie mechanizmów odporności na bakteriofagi
Bakteriofagi to wirusy, które atakują bakterie. Bakterie są w stanie modyfikować swoje mechanizmy odpornościowe, by bronić się przed zakażeniem przez bakteriofagi. Natomiast bakteriofagi mogą wykształcać mechanizmy przeciwdziałające takiej nabytej odporności bakterii. To swego rodzaju ewolucyjny wyścig zbrojeń. Wykorzystując wiedzę na temat bakteriofagów, zespół finansowanego ze środków ERBN projektu DEFEND zamierza opracować skuteczne strategie terapeutyczne pozwalające zwalczać antybiotykooporne patogeny. Naukowcy zbadają, w jaki sposób układy odporności nabytej (CRISPR) i wrodzonej bakterii chronią je przed wirusami bakteryjnymi (fagami) na poziomie molekularnym, komórkowym i populacyjnym.
Cel
Microbes are engaged in an evolutionary arms-race with their viruses and have evolved a spectrum of adaptive and innate defense systems to limit viral predation. Mechanistic insights into defense systems have yielded truly revolutionary genetic tools ranging from CRISPR-based genome editing nucleases to restriction enzymes used for molecular cloning. Despite the ongoing effort to understand defense systems, many antiviral defense systems remain virtually unstudied in and outside their native microbial context, creating huge potential for scientific breakthroughs and development of further game changing applications.
In the timely research proposed here I aim to uncover how adaptive (CRISPR) and innate immune systems protect bacteria from bacterial viruses (phages) at the molecular, cellular and population level. Based on our exiting unpublished observation that extremely phage resistant pathogens in our bacterial strain collection are true collectors of defense systems, I propose to investigate the contribution of each defense system and cooperativity between defense systems for broad and specific bacteriophage resistance. I furthermore aim to determine the molecular mechanism of a dominant set of related innate immune systems found in clinical pathogens, and to reveal how individual phages achieve immune evasion.
To accomplish my goals, I plan to use an interdisciplinary approach combining state-of-the-art molecular microbiology and biophysics at the single molecule and single cell level, with bioinformatics and high-throughput synthetic genomics screens. The project may lead to fundamentally new insights into the mechanism and evolution of virus immunity and will further explore the genetic treasure trove at the interface of virus and host interactions. Our findings will have implications for controlling virus resistance, and will be vital to develop effective therapeutic strategies to treat antibiotic resistant pathogens based on bacteriophages.
Dziedzina nauki
Program(-y)
Temat(-y)
System finansowania
ERC-COG - Consolidator GrantInstytucja przyjmująca
2628 CN Delft
Niderlandy