Structure-Function Analysis and Protein Engineering of Cas13d for RNA Targeting Applications

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9:30am - 10:30am
Zoom ID: 962 7365 4335 Passcode: 072668
https://hkust.zoom.us/j/96273654335?pwd=N254OTRlWVJuZUtLbG9uTXgxeS81UT09

ABSTRACT

Over the past decade, programmable Cas9 nucleases have revolutionized basic research and clinical applications. However, compared to Cas9-based DNA targeting tools, there is a lack of simple and effective tools for studying and manipulating RNA. The Type VI CRISPR-Cas13 system is currently the only known efficient programmable system exclusively targeting RNA. My research is focused on the type VI-D effector protein Cas13d, which is one of the smallest effectors in the Cas13 family, making it more advantageous for packaging into adeno-associated viruses. We utilized cryo-electron microscopy (cryo-EM), biochemical approaches, and hydrogen-deuterium exchange mass spectrometry to explore the conformational landscape of Cas13d during RNA processing, and utilized the structural insights to guide Cas13d protein engineering. Additionally, we established in vitro and cellular assays of using Cas13d to achieve mRNA knockdown, pre-mRNA splicing regulation, and RNA detection, providing proof-of-concept for future RNA-centric applications. Overall, our findings have the potential to significantly advance the field of transcriptome engineering and lead to more effective gene therapies.

https://hkust.zoom.us/j/96273654335?pwd=N254OTRlWVJuZUtLbG9uTXgxeS81UT09
活动形式
研讨会, 演讲, 讲座
讲者/ 表演者:
Cheng ZHANG
Scientist, Amgen Inc.

BIOGRAPHY

Cheng Zhang was trained as a structural biologist and biochemist. He received his Ph.D. in 2014 from National Institute of Biological Sciences, Beijing, where he utilized biochemical and structural biology techniques to investigate the functions of ribosome assembly factors. In 2016, he joined the Lyumkis lab at the Salk Institute for postdoctoral training. During his time there, he developed a method for characterizing small RNA structures using cryo-EM and collaborated with the Hsu lab to elucidate the structure-function relationship of the RNA-guided RNA-targeting CRISPR-Cas13d system. Since September 2021, Cheng has worked as a scientist at Amgen, where he conducted research at the intersection of targeted protein degradation and structural biology. He obtained high-resolution structures of various E3 ligase/ligand complexes that enabled bifunctional small molecule development. These experiences have led to Cheng’s current and future research interests, which will focus on applying state-of-the-art tools to understand CRISPR structural biology and develop novel therapeutics for targeted RNA degradation.

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英文
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研究生
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Bioscience and Biomedical Engineering Thrust, HKUST(GZ)
科学及科技
科大（广州）
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