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SUMMARY:The transformative genome engineering technology CRISPR-Cas9: less
 ons learned from bacteria - Dr Emmanuelle Charpentier
DTSTART:20160308T130000Z
DTEND:20160308T140000Z
UID:TALK61858@talks.cam.ac.uk
CONTACT:Ben Luisi
DESCRIPTION:The RNA-programmable CRISPR-Cas9 system has recently emerged a
 s a transformative technology in biological sciences\, allowing rapid and 
 efficient targeted genome editing\, chromosomal marking and gene regulatio
 n. In this system\, the endonuclease Cas9 or catalytically inactive Cas9 v
 ariants are programmed with single guide RNAs (sgRNAs) to target site-spec
 ifically any DNA sequence of interest given the presence of a short sequen
 ce (Protospacer Adjacent Motif\, PAM) juxtaposed to the complementary regi
 on between the sgRNA and target DNA. The system is efficient\, versatile a
 nd easily programmable.\n\nOriginally\, CRISPR-Cas is an RNA-mediated adap
 tive immune system that protects bacteria and archaea from invading mobile
  genetic elements (phages\, plasmids). Short crRNA (CRISPR RNA) molecules 
 containing unique genome-targeting spacers commonly guide Cas protein(s) t
 o invading cognate nucleic acids to affect their maintenance. CRISPR-Cas h
 as been classified into three main types and further subtypes. CRISPR-Cas9
  originates from the type II CRISPR-Cas system that has evolved unique mol
 ecular mechanisms for maturation of crRNAs and targeting of invading DNA\,
  which my laboratory has identified in the human pathogen Streptococcus py
 ogenes. During the step of crRNA biogenesis\, a unique CRISPR-associated R
 NA\, tracrRNA\, base pairs with the repeats of precursor-crRNA to form ant
 i-repeat-repeat dual-RNAs that are cleaved by RNase III in the presence of
  Cas9 (formerly Csn1)\, generating mature tracrRNA and intermediate forms 
 of crRNAs. Following a second maturation event\, the mature dual-tracrRNA-
 crRNAs guide the endonuclease Cas9 to cleave cognate target DNA and thereb
 y affect the maintenance of invading genomes. We have shown that the endon
 uclease Cas9 can be programmed with sgRNAs mimicking the natural dual-trac
 rRNA-crRNAs to target site-specifically any DNA sequence of interest. Base
 d on this harnessing principle\, we proposed that RNA-programmable Cas9 co
 uld be useful as a versatile system for genome editing in cells of all thr
 ee kingdoms of life for biotechnological\, biomedical and gene-therapeutic
  purposes. As demonstrated by a large number of studies published over the
  last 2 years\, DNA targeting by CRISPR-Cas9 has been quickly and broadly 
 adopted by the scientific community to edit and silence genomes in a large
  variety of cells and organisms\, including human cells\, plants and mice.
  I will discuss the biological roles of CRISPR-Cas9\, the mechanisms invol
 ved\, the evolution of type II CRISPR-Cas components in bacteria and the a
 pplications of CRISPR-Cas9 as a novel genome engineering technology.\n\n
LOCATION:Department of Biochemistry\, Sanger Building Lecture Theatre
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