Research Projects
RNA Biology and Genome Engineering

We aim to understand RNA-based gene expression regulation mechanisms and to develop new technologies that can be used in biology and medicine. We apply an integrative approach by combining CRISPR-Cas systems, high-throughput sequencing, and human cell-based protein purification.

On-going projects:

1. Small RNA-based high-throughput screening (coupled with CRISPR systems)
2. Transposases and transposable elements for genome engineering

Previous studies:

1. A comprehensive model for primary microRNA processing (Molecular Cell 2019)
   In the recent work, we tested ~40,000 primary microRNA variants using high-throughput sequencing and elucidated the comprehensive processing rules of DROSHA. Therefore, now we know how DROSHA accurately finds the cleavage site on primary microRNAs, and we can use this information for designing short hairpin RNAs (shRNAs) to regulate genes of interest specifically.
2. The first crystal structure of DROSHA (Cell 2016)
   MicroRNAs are ~22-nt-long RNAs that regulate the expression of specific mRNAs in diverse biological and pathological contexts. In the canonical pathway, a primary transcript of microRNA is sequentially cleaved by DROSHA and DICER to generate a mature microRNA. Understanding the processing mechanism of DROSHA is crucial because the DROSHA cleavage step determines the target specificity of microRNA. Although DROSHA had been identified as a microRNA biogenesis factor more than a decade ago, the structure of DROSHA was not available because no group had succeeded in the purification of a soluble and homogeneous DROSHA protein. In contrast, by using an optimised human cell expression system and deep knowledge on the biochemical property of DROSHA, we successfully purified the DROSHA protein and solved its crystal structure. The structure enabled us to start the complete understanding of the substrate recognition mechanism of DROSHA. The paper was praised by the Cell referees as ‘a very welcome addition to the microRNA field’s canon’ and ‘an important milestone.’
3. Whole RNA-binding protein repertoire of embryonic stem cells (Nature Structural & Molecular Biology 2013)
   RNA-binding proteins regulate the gene expression program, and many of them are linked to human diseases. In spite of their biological significance, our understanding of RNA-binding proteins had been limited to proteins with known RNA-binding domains. To reveal the comprehensive repertoire of RNA-binding proteins in embryonic stem cells, We carried out an experiment called ‘interactome capture’ in collaboration with the Matthias Hentze group at EMBL. The interactome capture utilises UV light to induce covalent crosslinks between RNA and nearby proteins, and the RNA-crosslinked proteins are purified and identified by mass spectrometry. As a result, We reported 555 RNA-binding proteins including a subset of stem cell-specific novel RNA-binding proteins. This paper has been cited >200 times and served as one of the three core datasets for a mammalian RNA-binding protein list (Nature Reviews Genetics 2014, 15:829).

Dr SC Kwon, School of Biomedical Sciences

Biography
chul@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.