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Investigation of conformational dynamics involved in genome editing events by CRISPR-Cpf1

Research Scholar

Chun Chan, PhD candidate, City University of Hong Kong (Hong Kong)
Xiaolin Cheng, faculty mentor

Background

  • Hometown: Hong Kong
  • Degrees received: PhD in computational biophysics from City University of Hong Kong.

What is the issue or problem addresses in your research?

CRISPR (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) proteins are part of the adaptive immune system of bacteria and archaea. We are interested in rationally modifying the CRISPR-Cpf1 system to improve its genome editing efficiency. The target efficiency and specificity of the CRISPR technology are influenced by multiple factors. In particular, several guide RNA design strategies have been proposed, together with the tools to optimize the design.

What methodology did you use in your research?

Our specific objective is to first perform large-scale molecular dynamics (MD) simulations to elucidate various conformational states involved in the Cpf1 catalysis and the interconversion rates between different states. We further aim to use these MD simulations to uncover the molecular mechanisms underlying the higher genome editing efficiency of certain crRNAs.

What are the purpose/rationale and implications of your research?

We will systematically explore how the incorporation of chemically and structurally modified nucleotides in crRNAs may affect the genome editing efficiency and off-target effects and to establish comprehensive structure-activity (genome editing efficiency) relationships of crRNA analogs.