Project Details
Projekt
Metagenomic data mining for the Analysis of CRISPR/Cas-Systems
Applicant
Professor Dr. Björn Voß
Subject Area
Bioinformatics and Theoretical Biology
Microbial Ecology and Applied Microbiology
Microbial Ecology and Applied Microbiology
Term
since 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 405973696
The discovery of a prokaryotic, adaptive immune system, the so called CRISPR-Cas, has revolutionised genetic engineering. The underlying mechanism makes it possible to edit genomic sequences with nucleotide precision, the insertion of genetic material at precisely defined positions, and the accurate deletion of unwanted genomic stretches.The original function of these systems in bacteria and archaea is the defence against invading DNA, such as viruses and plasmids, and more importantly to confer immunity against these elements. The specificity of CRISPR-Cas is mediated by the so called CRISPR RNAs (crRNAs) that are complementary to the foreign DNA. These crRNAs form a complex with the Cas proteins that recognises the invading DNA and one of the Cas proteins, the Cas endonuclease, cuts the DNA, thereby promoting its degradation. Variants of CRISPR-Cas systems could be identified that are involved in gene regulatory functions in the cell.The actual challenge in the analysis of CRISPR-Cas systems is to find targets. Because of the fact that CRISPR-Cas is a defence system against foreign DNA, the targeted entities are under a high selective pressure to circumvent this targeting. If they manage to escape, the targeted region has acquired mutations, which hinders their finding based on sequence similarity. If they are unsuccessful to escape, they become extinct. For these reasons, and because viral genomes are underrepresented in existing sequence databases, the search for CRISPR-Cas targets is challenging. Here, metagenomic data have the advantage that they represent a genomic snapshot of a defined habitat at a defined timepoint. Therefore, they likely also contain information about virus-host interactions, as they occur in course of a CRISPR-Cas response to infection. Additionally, the vast majority of prokaryotic species is not culturable, such that metagenomic data also offers the potential to increase the diversity of known CRISPR-Cas systems.In the proposed project we want to perform a comprehensive analysis of metagenomic data, with the clear aim to identify general features of CRISPR-Cas systems. For example, we will be able to address questions, such as if the defence against invading DNA is the main function of CRISPR-Cas systems, or if other functions, e.g. gene regulation, are more common than expected.
DFG Programme
Priority Programmes
