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REMEMBER SIGNED

Adaptive immunity in prokaryotes: how Bacteria do not forgive and do not forget their enemies

Total Cost €

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EC-Contrib. €

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Partnership

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 REMEMBER project word cloud

Explore the words cloud of the REMEMBER project. It provides you a very rough idea of what is the project "REMEMBER" about.

pressure    escherichia    incorporation    hypothesis    dna    co    phenomenon    environment    enigmatic    prevent    combination    supposition    constant    degenerate    mutated    bacterial    imaging    viruses    either    implies    arms    infections    cas    region    integrating    escape    types    perfectly    organic    invading    potentiate    mechanism    heavily    crispr    driving    revisiting    foes    treat    protein    inhibit    living    therapeutic    guided    microbes    genetic    threats    molecule    host    resistance    hostile    impair    natural    locus    treatments    point    screen    ecosystems    administered    single    mutations    invaders    rnas    complexes    coli    primed    molecules    restore    differentially    biochemical    huge    immunity    discovery    mount    antibiotic    evolutionary    priming    sequences    relatively    cells    hosts    race    universal    immune    structural    rna    remembers    trigger    survive    agents    resistant    functions    degradation    memory    remarkable    invader    benefit    matching    made    adaptive    guide   

Project "REMEMBER" data sheet

The following table provides information about the project.

Coordinator
TECHNISCHE UNIVERSITEIT DELFT 

Organization address
address: STEVINWEG 1
city: DELFT
postcode: 2628 CN
website: www.tudelft.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Project website http://www.brounslab.org
 Total cost 1˙499˙183 €
 EC max contribution 1˙499˙183 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    TECHNISCHE UNIVERSITEIT DELFT NL (DELFT) coordinator 1˙373˙296.00
2    WAGENINGEN UNIVERSITY NL (WAGENINGEN) participant 125˙886.00

Map

 Project objective

Microbes in natural ecosystems are under constant evolutionary pressure from viruses. To survive in this hostile environment microbes have evolved an adaptive immune system called CRISPR-Cas. The immune system is based on incorporation of invader DNA sequences in a memory locus (CRISPR), the formation of guide RNAs from this locus, and the degradation of invading target DNA using CRISPR RNA-guided protein complexes. Invaders escape immunity by making point mutations in the targeted region of their DNA, but hosts quickly restore immunity by integrating new memory sequences against the same invader in a process called priming. Recently, I have made the remarkable discovery that hosts mount a primed immune response even when facing heavily mutated invaders. This implies that the memory of the CRISPR-Cas system not only functions in the short term against relatively recent threats, but also remembers a range of revisiting old foes in the long term, providing a huge evolutionary benefit for the host in the arms race with their invaders. This proposal sets out to determine the mechanism of the enigmatic process of primed memory formation against heavily mutated invaders. Using a combination of genetic, biochemical and structural approaches, including state-of-the-art single molecule imaging of CRISPR immunity in living Escherichia coli cells, I will investigate the driving hypothesis that perfectly matching and degenerate targets are differentially recognized, and trigger either target DNA degradation or priming. Moreover, I will test the supposition that degenerate priming is a universal phenomenon among different CRISPR-Cas types. If this is the case, degenerate priming will impair the use of viruses as therapeutic agents to treat antibiotic resistant bacterial infections. To prevent CRISPR resistance I propose to screen for organic molecules that inhibit the formation of CRISPR resistance. These molecules can be co-administered with viruses to potentiate treatments.

 Publications

year authors and title journal last update
List of publications.
2015 John van der Oost, Stan J. J. Brouns
CRISPR sabotage
published pages: 1-3, ISSN: 1474-760X, DOI: 10.1186/s13059-015-0820-0
Genome Biology 16/1 2019-05-29
2016 Tim Künne, Sebastian N. Kieper, Jasper W. Bannenberg, Anne I.M. Vogel, Willem R. Miellet, Misha Klein, Martin Depken, Maria Suarez-Diez, Stan J.J. Brouns
Cas3-Derived Target DNA Degradation Fragments Fuel Primed CRISPR Adaptation
published pages: 852-864, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2016.07.011
Molecular Cell 63/5 2019-05-29
2015 Chaoyou Xue, Arun S. Seetharam, Olga Musharova, Konstantin Severinov, Stan J. J. Brouns, Andrew J. Severin, Dipali G. Sashital
CRISPR interference and priming varies with individual spacer sequences
published pages: 10831-10847, ISSN: 0305-1048, DOI: 10.1093/nar/gkv1259
Nucleic Acids Research 43/22 2019-05-29
2015 Kira S. Makarova, Yuri I. Wolf, Omer S. Alkhnbashi, Fabrizio Costa, Shiraz A. Shah, Sita J. Saunders, Rodolphe Barrangou, Stan J. J. Brouns, Emmanuelle Charpentier, Daniel H. Haft, Philippe Horvath, Sylvain Moineau, Francisco J. M. Mojica, Rebecca M. Terns, Michael P. Terns, Malcolm F. White, Alexander F. Yakunin, Roger A. Garrett, John van der Oost, Rolf Backofen, Eugene V. Koonin
An updated evolutionary classification of CRISPR–Cas systems
published pages: 722-736, ISSN: 1740-1526, DOI: 10.1038/nrmicro3569
Nature Reviews Microbiology 13/11 2019-05-29
2017 Simon A. Jackson, Rebecca E. McKenzie, Robert D. Fagerlund, Sebastian N. Kieper, Peter C. Fineran, Stan J. J. Brouns
CRISPR-Cas: Adapting to change
published pages: eaal5056, ISSN: 0036-8075, DOI: 10.1126/science.aal5056
Science 356/6333 2019-05-29
2018 Sebastian N. Kieper, Cristóbal Almendros, Juliane Behler, Rebecca E. McKenzie, Franklin L. Nobrega, Anna C. Haagsma, Jochem N.A. Vink, Wolfgang R. Hess, Stan J.J. Brouns
Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation
published pages: 3377-3384, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.02.103
Cell Reports 22/13 2019-05-03
2018 Marnix Vlot, Franklin L. Nobrega, Che F. A. Wong, Yue Liu, Stan J. J. Brouns
Complete Genome Sequence of the Escherichia coli Phage Ayreon
published pages: , ISSN: 2169-8287, DOI: 10.1128/genomea.01354-17
Genome Announcements 6/2 2019-05-03
2018 Franklin L. Nobrega, Marnix Vlot, Patrick A. de Jonge, Lisa L. Dreesens, Hubertus J. E. Beaumont, Rob Lavigne, Bas E. Dutilh, Stan J. J. Brouns
Targeting mechanisms of tailed bacteriophages
published pages: 760 - 773, ISSN: 1740-1526, DOI: 10.1038/s41579-018-0070-8
Nature Reviews Microbiology 16 2019-05-03
2018 Tim Künne, Yifan Zhu, Fausia da Silva, Nico Konstantinides, Rebecca E McKenzie, Ryan N Jackson, Stan JJ Brouns
Role of nucleotide identity in effective CRISPR target escape mutations
published pages: 10395-10404, ISSN: 0305-1048, DOI: 10.1093/nar/gky687
Nucleic Acids Research 46/19 2019-05-03
2018 Luuk Loeff, Stan J.J. Brouns, Chirlmin Joo
Repetitive DNA Reeling by the Cascade-Cas3 Complex in Nucleotide Unwinding Steps
published pages: 385-394.e3, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.03.031
Molecular Cell 70/3 2019-05-03
2017 Marnix Vlot, Joep Houkes, Silke J A Lochs, Daan C Swarts, Peiyuan Zheng, Tim Kunne, Prarthana Mohanraju, Carolin Anders, Martin Jinek, John van der Oost, Mark J Dickman, Stan J J Brouns
Bacteriophage DNA glucosylation impairs target DNA binding by type I and II but not by type V CRISPR–Cas effector complexes
published pages: 873-885, ISSN: 0305-1048, DOI: 10.1093/nar/gkx1264
Nucleic Acids Research 46/2 2019-05-03
2018 Patrick A. de Jonge, Franklin L. Nobrega, Stan J.J. Brouns, Bas E. Dutilh
Molecular and Evolutionary Determinants of Bacteriophage Host Range
published pages: , ISSN: 0966-842X, DOI: 10.1016/j.tim.2018.08.006
Trends in Microbiology 2019-05-03
2018 Ana Rita Costa, Stan J. J. Brouns, Franklin L. Nobrega
Complete Genome Sequences of Two T4-Like Escherichia coli Bacteriophages
published pages: , ISSN: 2169-8287, DOI: 10.1128/genomea.00586-18
Genome Announcements 6/26 2019-05-03

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