MSOPGDM · Mechanistic studies of prokaryotic genome defense mechanisms
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-03-31
- EU contribution
- €191,149
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Mechanistic studies of prokaryotic genome defense mechanisms
Prokaryotes are constantly threatened by a plethora of viruses (bacteriophages) and other genetic invaders. The evolutionary pressure associated with this host-parasite conflict has resulted in the emergence of numerous defense mechanisms that act on various stages of the bacteriophage life cycle. These defense mechanisms include restriction-modification enzymes and CRISPR-Cas systems, which have been proven to be useful tools for genome engineering. The current project set out to provide a mechanistic basis for immunity of two novel and uncharacterized prokaryotic defense systems. To address this question, we aimed to determine the molecular structures and biochemical activities of key effector proteins that are encoded by these systems. Deciphering these mechanisms will be important for our fundamental understanding of these systems that shape host-invader interactions and may additionally provide new tools to expand the genome engineering toolbox
Data: CORDIS, © European Union
Project objective
The constant biological arms race between prokaryotic organisms and invading mobile genetic elements has resulted in the evolution of sophisticated genome defense mechanisms. The genes encoding for immunity commonly reside in genomic clusters known as defense islands that are in the vicinity of other host-defense loci. Recent studies of defense islands have uncovered ten novel host defense mechanisms whose molecular mechanisms remain elusive at present. The proposed project aims to provide a mechanistic basis for genetic immunity in two novel host defense systems: Druantia and Shedu. These systems contain genes encoding nucleases, ATPases and helicases, which strongly suggests that they provide immunity by directly targeting invading nucleic acids. To unravel the molecular mechanisms that underpin immunity in these systems, I will apply a highly interdisciplinary approach by using biochemical and state-of-the-art structural biology techniques, including high-throughput X-ray crystallography, cryo-EM and crosslink-coupled mass spectrometry. Understanding these mechanisms will provide fundamentally new insights into prokaryotic biology and the evolution of host-virus defense systems. Furthermore, these studies might uncover novel molecular activities that may be exploited for use as genetic engineering tools.
Original text from CORDIS.
Participants
- UNIVERSITAT ZURICH · ZurichCoordinatorSwitzerland
Links
Data: CORDIS, © European Union