Leslie BEH

Genome and Epitranscriptome Engineering

PhD – Biology, Princeton University, USA

LinkedIn: https://www.linkedin.com/in/leslie-beh/

SUMMARY

Leslie Beh is a Principal Investigator at the Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR) since September 2022.

Prior to joining IMCB, Leslie pursued a career in industry, joining Illumina to lead a research group for developing novel epigenetics assays. Driven by the desire to do biological research and make an impact on students, Leslie joined IMCB, A*STAR as a Principal Investigator.

Leslie earned an A.B. in Biology at Harvard University as a John Harvard scholar, where he trained with Nicole Francis on the biochemistry of Polycomb group proteins. He then obtained his A.M. and PhD in Biology from Princeton University as a Petrie fellow with Laura Landweber and Tom Muir, where he developed methods for assembling synthetic chromosomes with custom epigenetic modifications. Using genomics and biochemical fractionation approaches, he identified a novel DNA methyltransferase complex with evolutionary links to the canonical RNA N6-methyladenosine (m6A) methyltransferase, METTL3/14. Following this, Leslie embarked on a short postdoctoral stint with Sam Sternberg at Columbia University, where he used genomic, structural, and biochemical approaches to study CRISPR-Cas systems that mediate RNA-guided DNA integration.

AWARDS & GRANTS

2024: National Research Foundation Fellowship (NRFF Class of 2024)
2023: National Medical Research Council Open Fund – Young Individual Research Grant (OF-YIRG)
2015: Petrie Fellow (Princeton University)

RESEARCH

Mechanistic studies and applications of DNA and RNA modifying enzymes
DNA and RNA-modifying enzymes constitute the bedrock of modern molecular biology, spanning restriction enzymes to CRISPR-Cas systems. There still exist vast troves of enzymes with spectacular biochemical activities that remain to be discovered and repurposed for biotechnology. Our lab seeks to identify these enzymes, understand their mechanistic basis of function, and harness them as new tools for curing human diseases. We adopt a diverse set of techniques, ranging from protein purification and biochemical assays to genome-wide studies of enzymatic activity in human cells. One active area of research in our lab involves engineering enzymes for understanding mRNA modifications in human disease.

PUBLICATIONS

Selective TnsC recruitment enhances the fidelity of RNA-guided transposition.
Hoffmann, F. T.*, Kim, M.*, Beh, L. Y.*, Wang, J., Vo, P. L. H., Gelsinger, D. R., George, J. T., Acree, C., Mohabir, J. T., Fernández, I. S., & Sternberg, S. H. (2022)
Nature. 609(7926): 384-393
*Co-first authors
Evolutionary and mechanistic diversity of Type I-F CRISPR-associated transposons.
Klompe, S. E., Jaber, N., Beh, L. Y., Mohabir, J. T., Bernheim, A., & Sternberg, S. H. (2022)
Mol Cell. 82(3): 616–628
Identification of a DNA N6-Adenine Methyltransferase Complex and Its Impact on Chromatin Organization.
Beh, L. Y.*, Debelouchina, G. T., Clay, D. M., Thompson, R. E., Lindblad, K. A., Hutton, E. R., Bracht, J. R., Sebra, R. P., Muir, T. W., & Landweber, L. F. (2019)
Cell. 177(7): 1781–1796
*First author. Cover Story

Functional crosstalk between histone H2B ubiquitylation and H2A modifications and variants.
Wojcik, F., Dann, G. P., Beh, L. Y., Debelouchina, G. T., Hofmann, R., & Muir, T. W. (2018)
Nat Commun. 9(1): 1394

DNA-guided establishment of nucleosome patterns within coding regions of a eukaryotic genome.
Beh, L. Y.*, Müller, M. M., Muir, T. W., Kaplan, N., & Landweber, L. F. (2015)
Genome Res. 25(11): 1727–1738
*First author, Co-Corresponding authors

A core subunit of Polycomb repressive complex 1 is broadly conserved in function but not primary sequence.
Beh, L. Y.*, Colwell, L. J., & Francis, N. J. (2012)
Proc Natl Acad Sci U S A. 109(18): E1063–E1071
*First author

Leslie BEH

A*STAR celebrates International Women's Day