From: "Thomas Jacobs" <thomas.jacobs@psb.vib-ugent.be> To: "research" <research@psb.vib-ugent.be> Cc: "seminar" <seminar@psb.vib-ugent.be> Sent: Monday, October 21, 2024 10:16:22 AM Subject: Re: Special Solvay Institutes Scholar seminar-- Alexis Komor Nov 6

Dear all,

Just a reminder about the special seminar on November 6. Please see the attached flyer.

cheers,

Tom

----- On 7 Oct, 2024, at 09:23, Thomas Jacobs <thomas.jacobs@psb.ugent.be> wrote:

Dear all,

On November 6, Alexis Komor will be visiting VIB-UGent as part of the prestigious Solvay Institutes New Horizons Lectures in chemistry http://www.solvayinstitutes.be/html/new_horizons.html . Alexis is probably best known for her development of CRISPR Base Editing technology during her postdoc in David Liu's lab at the Broad (more information below). I am currently putting the program together and are looking for any PIs, postdocs or students who would be interested to meet with her. If you are interested, please send me an email. Students and postdocs, we will also arrange a lunch to meet and discuss with Alexis.

More details on her research and talk below.

cheers,

Tom

Dr. Alexis Komor, Assistant Professor, UCSD

Title: Engineering and Evolving Nucleic Acid Modifying Enzymes

Base editors (BEs) are comprised of a catalytically inactivated Cas9 (dCas9 or Cas9n) tethered to a single-stranded DNA (ssDNA) modifying enzyme, which directly chemically modifies target nucleobases within a “base editing window”. Two classes of base editors exist, which use cytosine and adenine deamination chemistries to catalyze the conversion of C•G base pairs to T•A (CBEs), and A•T base pairs to G•C (ABEs), respectively. These transition mutations (purine-purine or pyrimidine-pyrimidine) are mediated by uracil (cytosine deamination) or inosine (adenine deamination) intermediates, and occur with high efficiencies (up to 90% conversion) with little to no competing indel formation. Expansion of the BE toolbox to include transversion editors will require engineering of new nucleic acid editing enzymes. As ABEs were developed by engineering and evolving a tRNA adenosine deaminase enzyme, TadA, into a ssDNA adenosine deaminase enzyme, TadA7.10, the development of future BEs may be accomplished by converting additional tRNA modifying enzymes into ssDNA editing enzymes. In this talk I will describe my lab’s efforts to mechanistically understand how current BE enzymes function. The enhanced understanding of how known DNA editing enzymes function, and in particular how wtTadA was converted into TadA7.10, can inform the development of future DNA editing enzymes.

Background

The Komor lab focuses on four main research programs: 1, Development Of New Precision Genome Editing Methodologies; 2, Mechanistic Characterization Of Nucleic Acid Editing Enzymes; 3, Mechanistic Understanding Of Cellular Processing Of Genome Editing Intermediates; and 4, Clinical Characterization Of Human Genetic Variants.

Alexis received her B. S. degree in chemistry from the University of California, Berkeley in December of 2008. She then joined the lab of Jacqueline K. Barton at the California Institute of Technology for her doctoral studies. While at Caltech, she worked as an NSF Graduate Research Fellow on the design, synthesis, and study of DNA mismatch-binding metal complexes and received her Ph.D. in 2014. She pursued postdoctoral work as a Ruth L. Kirschstein NIH Postdoctoral Fellow in the laboratory of David R. Liu, where she developed base editing, a new approach to genome editing that enables the direct, irreversible chemical conversion of one target DNA base into another in a programmable manner, without requiring double-stranded DNA backbone cleavage. Alexis joined the Department of Chemistry and Biochemistry at the University of California at San Diego in 2017, where her lab develops and applies new precision genome editing techniques to the functional genomics field. Alexis’s contributions in teaching, mentoring, and research have been recognized through many awards, including the Cottrell Scholar Award, the “Talented 12” recognition by C&EN News, an NSF Faculty Early Career Development (CAREER) award, an NIH early stage investigator Maximizing Investigators’ Research Award (MIRA), and a “40 under 40” recognition in healthcare by Fortune Magazine.

Thomas Jacobs - Group leader Plant Genome Editing

VIB-UGent Center for Plant Systems Biology Ghent University Technologiepark-Zwijnaarde 71 - 9052 Ghent - Belgium Tel. +32(0)9 331 38 60 [ http://www.psb.ugent.be/ | www.psb.ugent.be ]

Genome editing, cutting-edge technology for a sustainable agriculture