BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Center for RNA Biomedicine - ECPv6.16.2//NONSGML v1.0//EN
CALSCALE:GREGORIAN
METHOD:PUBLISH
X-ORIGINAL-URL:https://rna.umich.edu
X-WR-CALDESC:Events for Center for RNA Biomedicine
REFRESH-INTERVAL;VALUE=DURATION:PT1H
X-Robots-Tag:noindex
X-PUBLISHED-TTL:PT1H
BEGIN:VTIMEZONE
TZID:America/Detroit
BEGIN:DAYLIGHT
TZOFFSETFROM:-0500
TZOFFSETTO:-0400
TZNAME:EDT
DTSTART:20220313T070000
END:DAYLIGHT
BEGIN:STANDARD
TZOFFSETFROM:-0400
TZOFFSETTO:-0500
TZNAME:EST
DTSTART:20221106T060000
END:STANDARD
BEGIN:DAYLIGHT
TZOFFSETFROM:-0500
TZOFFSETTO:-0400
TZNAME:EDT
DTSTART:20230312T070000
END:DAYLIGHT
BEGIN:STANDARD
TZOFFSETFROM:-0400
TZOFFSETTO:-0500
TZNAME:EST
DTSTART:20231105T060000
END:STANDARD
BEGIN:DAYLIGHT
TZOFFSETFROM:-0500
TZOFFSETTO:-0400
TZNAME:EDT
DTSTART:20240310T070000
END:DAYLIGHT
BEGIN:STANDARD
TZOFFSETFROM:-0400
TZOFFSETTO:-0500
TZNAME:EST
DTSTART:20241103T060000
END:STANDARD
END:VTIMEZONE
BEGIN:VEVENT
DTSTART;TZID=America/Detroit:20231120T160000
DTEND;TZID=America/Detroit:20231120T170000
DTSTAMP:20260525T021557
CREATED:20230801T170218Z
LAST-MODIFIED:20231030T193356Z
UID:11214-1700496000-1700499600@rna.umich.edu
SUMMARY:RNA Innovation Seminar: George Lisi\, Brown University
DESCRIPTION:“The Invisible Dance of CRISPR-Cas9 through Molecular Space and Time”\nGeorge Lisi\, Ph.D.\nThomas J. & Alice M. Tisch Assistant Professor\nDepartment of Molecular Biology\, Cell Biology & Biochemistry\nBrown University \n  \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: This talk will focus on long-range signaling in CRISPR-Cas9\, a cutting-edge genome editing tool. The transformative potential of Cas9 as a precision therapeutic cannot be realized without an understanding of its interdomain communication and the mitigation of deleterious off-target cleavage\, which is being characterized at the atomic level in the group. A series of vignettes will highlight NMR studies of Cas9 through a “divide-and-conquer” approach using engineered protein constructs and first demonstrate that multi-timescale motions in the catalytic nuclease of Cas9 propagates chemical information that regulates cleavage of double-stranded DNA. The talk will also highlight specificity-enhancing mutations in Cas9 that rewire its regulatory mechanism and RNA interactions at the molecular level to mitigate off-target DNA cleavage. Critical energetics of the mechanism will be discussed\, including the importance of metal ions and the protonation state of the catalytic histidine\, studied via catalytic pocket mutations that limit conformational sampling of the Cas9 active state. Lastly\, insight from canonical Cas9s will be expanded to highly stable thermophiles that are more promising for genome engineering and offer tunable high-temperature DNA editing and RNA binding. The underlying chemistry and atomic level dynamics of Cas9 will be linked to its nucleic acid interactions and biological outcomes\, hopefully opening new avenues for intuitive manipulation of its function and precision therapeutic properties.
URL:https://rna.umich.edu/events/george-lisi/
LOCATION:MI
END:VEVENT
END:VCALENDAR