SPP 2141:  Much more than defence: the multiple functions and facets of CRISPR-Cas

• Subject Area: Medicine ; Biology ; Humanities ; Mathematics
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 360987069

In the frame of this priority programme 21 groups cooperate towards the common goal to identify and characterise CRISPR-Cas functions beyond defence in a concerted action. The CRISPR-Cas system has been identified as a prokaryotic defence system more than ten years ago and today, we know that this molecular machine can also carry out other functions beyond defence. The CRISPR-Cas systems or one of its components have been reported to be involved in DNA repair, virulence regulation and group behaviour to name a few. Up to date new CRISPR-Cas functions have primarily been discovered fortuitously and systematic approaches to detect new functions are lacking. The aim of this priority programme is to systematically search for functions of the CRISPR-Cas system beyond defence. The synergy provided by this priority programme is required to effectively achieve the set goals of unravelling and identifying new and additional CRISPR-Cas functions. A team of renowned scientists from different disciplines, such as microbiology, genetics, medical microbiology, biochemistry, biophysics, bioinformatics, ecology, structural biology, molecular dynamics, single-molecule localisation microscopy and single-molecule biochemistry, makes this programme truly interdisciplinary and will guarantee a successful outcome. The newly revealed functions of the CRISPR-Cas system promise exciting biological discoveries and surprising insights into the new activities and will open several novel avenues of research. The two major goals of this concerted priority programme are: (1) The identification and investigation of new CRISPR-Cas functions beyond defence using model representatives of archaea and bacteria. (2) The elucidation of the molecular mechanisms underlying these novel functions using state-of-the-art methods. The programme will be supplemented by a public outreach module to communicate the science of CRISPR-Cas to society in a comprehensible manner and to facilitate the discussion of controversial issues with the public (e.g., for human genome editing applications).

• DFG Programme: Priority Programmes
• International Connection: Israel, Netherlands, United Kingdom

Projects

• Anti-plasmid and CRISPRi activity of a Pseudomonas oleovorans Type IV-A CRISPR-Cas system (Applicant Randau, Lennart )
• Characterizing CRISPR-Cas systems with non-defensive functions (Applicant Beisel, Chase )
• Coordination Funds (Applicant Marchfelder, Anita )
• CRISPR-Cas functions beyond defence in haloarchaea (Applicant Marchfelder, Anita )
• CRISPR-Cas functions in the stress response of Rhodobacter capsulatus (Applicant Klug, Gabriele )
• CRISPR vs. CRISPR - how mobile CRISPR-Cas systems interact with and sometimes replace host systems (Applicant Gophna, Uri )
• Cross-talk and extensive rewiring of CRISPR-Cas systems with the cellular regulatory machinery in cyanobacteria (Applicant Hess, Wolfgang R. )
• Elucidation of the molecular mechanism of Cas-endonucleases from bacteria and cyanobacteria (Applicant Schneider, Sabine )
• Evolutionary dynamics and phylogenetic inference of CRISPR systems in prokaryotic populations (Applicant Baumdicker, Franz )
• Function and Evolution of archaeal stand-alone cas genes and cas-related anti-CRISPR genes (Applicant Schmitz-Streit, Ruth Anne )
• Learning structures in the CRISPR-Cas system using deep learning architectures (Applicant McHardy, Alice C. )
• Mechanisms and functions of endogenous RNA-targeting by CRISPR-Cas9 in Campylobacter jejuni (Applicant Sharma, Cynthia Mira )
• Metagenomic data mining for the Analysis of CRISPR/Cas-Systems (Applicant Voß, Björn )
• Natural functions of CRISPR-Cas systems in Cyanobacteria (Applicant Wilde, Annegret )
• Prevalence, formation, and function of “extraneous” CRISPR RNAs derived from the extra repeat in CRISPR arrays (Applicants Beisel, Chase ;  Weinberg, Ph.D., Zasha )
• Public Relation Project: CRISPR/Cas - more than defense - Public Outreach (Applicant Ziegler, Heike )
• RNA processing and activation of Type IIIA CRISPR-Cas systems (Applicant Seidel, Ralf )
• Service Project: "CRISPR Bioinformatics" (Applicant Backofen, Rolf )
• Service Project: Mass spectrometric proteomic and structural proteomics on CRISPR-Cas of archaea and bacteria (Applicant Urlaub, Henning )
• Single-molecule analysis of non-canonical Cas9 ribonucleoprotein complexes and characterisation of archaeal solo-Cas4 protein variants (Applicant Grohmann, Dina )
• Structure and mechanism of CRISPR-Cas type IV systems (Applicant Bange, Gert )
• Studying protein organization and dynamics of the Type I-Fv CRISPR-Cas system of Shewanella putrefaciens CN-32 at a high spatiotemporal resolution in living cells (Applicant Endesfelder, Ulrike )
• The CRISPR/Cas system in Neisseria meningitidis and its potential role in host cell adhesion (Applicant Schoen, Christoph )

• Spokesperson: Professorin Dr. Anita Marchfelder