Structural insights into the mechanism of CRISPR-Cas9 genome editing
Event details
| Date | 10.11.2015 |
| Hour | 16:15 › 18:00 |
| Speaker |
Prof. Dr. Martin Jinek, Universität Zürich Bio: Martin Jinek was born in Czechoslovakia in 1979. He studied Chemistry and Natural Sciences at Trinity College, University of Cambridge (UK). In 2006, he received his PhD from the European Molecular Biology Laboratory (EMBL) in Heidelberg where he conducted his thesis in the lab of Dr. Elena Conti. He then moved to the University of California in Berkeley for postdoctoral research with Prof. Jennifer Doudna. Martin joined the Department of Biochemistry in February 2013 as Assistant Professor on tenure track. He is interested in the molecular mechanisms that orchestrate cellular regulation through protein-RNA interactions. His studies include biochemical and structural approaches to investigate these processes at the atomic level. |
| Location | |
| Category | Conferences - Seminars |
Chemical Biology Seminar Series
The CRISPR-Cas9 system provides a simple yet versatile technology for modifying the genetic information in cells and organisms and is set to revolutionize biotechnology and biomedicine. We previously showed that the CRISPR-associated protein Cas9 associates with an unusual dual-RNA guide structure and cleaves double-stranded DNA sequences complementary to a 20-nucleotide sequence in the guide RNA. Aiming to establish Cas9 as a genome editing tool, we also demonstrated that the enzyme can be programmed using single-molecule guide RNAs to induce double-strand DNA breaks in human cells, paving the way for RNA-guided genetic engineering using CRISPR-Cas9.
Our current work focuses on obtaining structural insights into the molecular mechanism of Cas9-mediated DNA cleavage, which is critically dependent on the presence of a short Protospacer Adjacent Motif (PAM) in the target DNA. Recently, we determined the structure of Cas9-sgRNA complex bound to a PAM-containing DNA target. The structure reveals how the PAM motif is read out by sequence-specific interactions and suggests a mechanism for PAM-dependent guide-target heteroduplex formation.
These studies provide the framework for understanding Cas9 function at the molecular level and for ongoing development of CRISPR-Cas9 for genetic engineering applications.
The CRISPR-Cas9 system provides a simple yet versatile technology for modifying the genetic information in cells and organisms and is set to revolutionize biotechnology and biomedicine. We previously showed that the CRISPR-associated protein Cas9 associates with an unusual dual-RNA guide structure and cleaves double-stranded DNA sequences complementary to a 20-nucleotide sequence in the guide RNA. Aiming to establish Cas9 as a genome editing tool, we also demonstrated that the enzyme can be programmed using single-molecule guide RNAs to induce double-strand DNA breaks in human cells, paving the way for RNA-guided genetic engineering using CRISPR-Cas9.
Our current work focuses on obtaining structural insights into the molecular mechanism of Cas9-mediated DNA cleavage, which is critically dependent on the presence of a short Protospacer Adjacent Motif (PAM) in the target DNA. Recently, we determined the structure of Cas9-sgRNA complex bound to a PAM-containing DNA target. The structure reveals how the PAM motif is read out by sequence-specific interactions and suggests a mechanism for PAM-dependent guide-target heteroduplex formation.
These studies provide the framework for understanding Cas9 function at the molecular level and for ongoing development of CRISPR-Cas9 for genetic engineering applications.
Links
Practical information
- Informed public
- Free
Organizer
- Prof. Beat Fierz
Contact
- beat.fierz@epfl.ch