Mapping the G-quadruplex in the human transcriptome

9 November 2015

Dr Kwok Chun Kit (Croucher Fellowship 2014) is working on the development and application of innovative molecular biology tools and next-generation sequencing technologies at Cambridge University.

Kwok is a chemist and molecular biologist who believes that scientists are on the brink of unlocking the secrets of ribonucleic acids. He is interested in developing next-generation sequencing technologies as well as chemical approaches to understand the structure-function relationship of ribonucleic acids at the genomic scale. Recently, his research started to examine the ribonucleic acid G-quadruplex structure nucleic acid sequences, which form four-stranded structures, and their functions.

Now a Croucher postdoctoral fellow, Kwok’s current research under Professor Shankar Balasubramanian FRS FMedSci at the University of Cambridge aims to answer a set of fundamental questions about ribonucleic acid G-quadruplexes, including but not limited to figuring out which transcripts they are found in; which binding partners, such as proteins, chromatin or other ribonucleic acids, they interact with; and their exact position inside a cell. Kwok said, “Solving these problems will help us to better understand the biological functions of the G-quadruplex in humans, as well as revealing if they play a key part in causing diseases and cancers. For instance, if they are found to exist in disease-causing genes, it is possible that they play a crucial role in the molecular basis of certain diseases.” They are already linked to some neurological diseases such as amytotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, which degenerates motor neurons, and fragile X syndrome, which causes developmental problems. The short-term aim of the research is to map the G-quadruplex in the human transcriptome for the first time, while the long-term goal is to develop molecular tools to target them specifically, with potential diagnostic and therapeutical applications. Kwok himself is interested in the diagnostic applications, which might include creating an assay which would emit a signal when binding to the G-quadruplex in order to aid the early detection of diseases.

During his time at the University of California, Kwok developed an interest in ribonucleic acids and chose to continue this research in his PhD work. Kwok explains, “Ribonucleic acids can do everything, so if there is something that can make life simpler, it’s ribonucleic acids.” He enjoys this subject as so little is known about it that researchers are constantly on the edge of the unknown. After completing his undergraduate degree at the Chinese University of Hong Kong, he returned to the United States for his PhD, which explored how ribonucleic acids structure is related to its function in a transcriptome-wide sense. This groundbreaking research provided the first evidence that in vivo ribonucleic acid structure regulates gene regulation pathways, which prior to this had only been speculated, in addition to being the first time ribonucleic acid structure in a cell was accurately determined. As a result, the Bevilacqua and Assmann labs established ‘DMS/SHAPE-LMPCR’, an in vivo RNA structure probing assay, and Structure-Seq, the first in vivo transcriptome-wide ribonucleic acid structure probing platform, which utilises chemical probing and next generation sequencing to report the structure of tens of thousands of transcripts simultaneously in the model plant organism Arabidopsis thaliana. These results were reported in journals such as Nature, Nature Communications, and Nature Protocols.

At the Cell Symposia, which will be held in Singapore in November of this year, Kwok will present his current research on the G-quadruplex, made possible by the support of the Croucher Foundation, who also nominated him to attend the 65th Lindau Nobel Laureates’ Meeting in Germany earlier this year. Kwok’s long-term ambition is to start his own research lab in Hong Kong with the aim of understanding more about ribonucleic acids and their roles in biological processes. He also hopes to help cultivate a stimulating learning and research environment in Hong Kong, particularly for students and young scientists.

Kwok gained his BSc in Chemistry from the Chinese University of Hong Kong in 2009, where he also achieved several awards such as the Swire Scholarship. Having enjoyed the different environment provided by his year abroad at the University of California, Los Angeles in 2007-2008, Kwok applied for a PhD program at Pennsylvania State University in the United States in 2009, where he expanded his interest in ribonucleic acid biology and plant biology research and was awarded the Alumni Association Dissertation Award from Pennsylvania State University. Following this, Kwok began a postdoctoral fellowship as a Croucher fellow (2014-2016) at the University of Cambridge, United Kingdom, where he studies G-quadruplexes and potential links to diseases and cancers, led by Professor Shankar Balasubramanian.

To view Kwok Chun Kit’s personal Croucher profile, please click here