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Protein and DNA (deoxyribonucleic acid) may sound familiar to everyone, but RNA (ribonucleic acid) is probably another story. In fact, RNA plays a pivotal role in many aspects, such as decoding the genetic codes stored in DNA and producing protein. Dr Kwok Chun Kit, Assistant Professor from the Department of Chemistry at City University of Hong Kong (CityU), is devoted to studying RNA. He hopes to reveal the structure of a specific type of RNA and its interactions in cells, as well as its biological functions and mechanism, in order to develop chemical and molecular tools for diagnostic and therapeutic applications.
Dr Kwok has received the “Croucher Innovation Awards” presented by the Croucher Foundation for his research on RNA. This is the first time CityU scholars receiving the award. And good things come in pairs: another young scholar from the Department of Biomedical Sciences has also received the award for her research on immune cells.
Dr Kwok felt glad and honoured to receive this award. He thanked the Croucher Foundation for the trust in his basic research on RNA. He also felt grateful that the Foundation has recognized the pioneering of his research project as well as his ability to carry out and complete it. He also thanked CityU, Department of Chemistry, and other funding agencies for their strong and consistent support for his research in terms of resources and funding.
Discover the unknown functions of RNA
The general understanding is that RNA only passively transcribes the information of protein production according to the genetic information stored in DNA. And then the protein produced maintains physiological functions. Dr Kwok has become deeply interested in RNA when he was studying PhD in the United States. He pointed out that in recent years, scientists have discovered that RNA not only transcribes genetic information, but also plays a regulatory role in the process of gene expression. RNA also orders protein production which can promote or suppress tumor growth. Even some virus replication and neurological diseases are also related to RNA.
Dr Kwok hopes to unravel the mystery of RNA: to understand its structure, the biochemical mechanisms behind its different functions, as well as its role in cell division and pathology. The first step of the research is to find out the RNA structure. But the conventional chemical biology technology was not that advanced in the early years, therefore scientists were unable to obtain sufficient genetic information about the RNA structure. So Dr Kwok and other researchers tried to blaze a new trail by combining conventional chemical biology technology with new high-throughput sequencing technology, and they successfully developed new technologies to identify the RNA structure.
Developing multiple new RNA high-throughput sequencing technologies
Over the years, Dr Kwok has been involved in developing different RNA high-throughput sequencing technologies, including structure-seq, rG4-seq, and COMRADES. In 2014, as a PhD student at Pennsylvania State University, he co-authored an article introducing “structure-seq” with his doctoral mentor and research team. The article was published in the highly prestigious scientific journal Nature, and even became one of the featured articles on the cover. “Structure-seq” is a high-throughput, genome-wide in vivo RNA structure probing method that can be used in any organism.
2014 was a rewarding year for Dr Kwok. Apart from his debut in Nature, he also won the Inventor Incentive Award, and the Alumni Association Dissertation Award presented by the Pennsylvania State University. In the same year, he caught the attention of the Croucher Foundation and commenced on a postdoctoral fellowship as a Croucher Fellow in University of Cambridge and started his research on RNA.
At Cambridge, Dr Kwok was inspired by his mentor and then delved into the mystery of RNA G-quadruplex, a special secondary structure formed by G-rich RNA sequences that fold into a four-stranded conformation. It can be a platform for protein binding and perform different functions. “At that time I was involved in developing rG4-seq high-throughput sequencing technology. I applied this technology and found the position of G-quadruplex in the RNA sequence, but its mechanism is still unknown,” he said. Their findings were published in the journal Nature Methods in 2016.
In October of the same year, he returned to Hong Kong from the United Kingdom and joined the Department of Chemistry at CityU. Here he has set up a laboratory to continue his research on G-quadruplex: explore its related protein, and investigate whether it is related to gene regulation, cell development as well as certain cancer genes so that it can become biomarkers and therapeutic targets.
Cancer links to long non-coding RNA
“As I have mastered the relevant high-throughput RNA sequencing technologies, why don't I apply them on different RNAs and see if I can find interesting discoveries? ” Therefore, Dr Kwok also set his sights on long non-coding RNAs (lncRNA) that he is also interested in.
Coding RNA is responsible for transcribing genetic information and producing proteins. Their quantity only accounts for less than 5% of all RNAs. The remaining 90% or more are non-coding RNA (ncRNA) that do not produce proteins. One type of non-coding RNAs is long non-coding RNA. “My research on long non-coding RNA is the focus of this Croucher Innovation Awards research project. We have a lot of non-coding RNAs in our bodies. They do not produce proteins, then what are their functions?” Dr Kwok said.
Dr Kwok pointed out that more than 15,000 long non-coding RNAs have been identified in the human body so far. Yet, functions are known in only about 200 of them. Also, recent studies have found that some cancers are linked to certain long non-coding RNAs. His research team will start with this and try to understand the structure of long non-coding RNA and its interactions with other substances such as proteins. His team will apply interdisciplinary research methods including chemical biology, molecular biology, structural biology, and genomics. They will also use high-throughput methods or develop new technologies to obtain more data. “Once we understand the mechanism, then we can try to use chemical and molecular tools to control it,” he said.
RNA research: the less popular one
Born and raised in Hong Kong, Dr Kwok has fallen in love with chemistry as he was inspired by his chemistry teacher in secondary school. He chose to major in chemistry at university without hesitation. While most of his classmates are now working in education or other industries, he is one of the few, if not the only, who has embarked on the journey of scientific research. Now at CityU, apart from concentrating on his research, he hopes to inspire the students’ interest in chemical and biological reactions related to DNA and RNA. The unique logo of Dr Kwok’s research group is printed on the lab coats of his research group students. It is a set of RNA patterns designed by his wife.
Dr Kwok said that the research community has always paid less attention to the importance of RNA, as compared with that of DNA and proteins, “I didn't know much about RNA when I was an undergraduate student. To introduce RNA to students, I am offering courses related to DNA and RNA at CityU. I hope they will be interested in related research.” To promote RNA education, Dr Kwok and other like-minded researchers founded the Hong Kong RNA Club (http://www.kitkwok.com/hk-rna-club.html) in 2017. The Club would regularly organize relevant seminars and symposia, and invite oversea scholars for sharing in Hong Kong.
Dr Kwok has received various awards for his outstanding performance, including the Selected Young Scientist Participant for the 65th Lindau Nobel Laureate Meeting in 2015, the Kan Tong Po International Visiting Fellowship of the Royal Society in 2017, and the President’s Award from CityU in 2019.
The Croucher Innovation Awards aims to identify a small number of exceptionally talented and internationally competitive scientists. It offers substantial support to these “rising stars” at a formative stage in their careers. It is designed to enable recipients to advance their expertise and engage in bold innovation, as well as to contribute to the development of education and research in Hong Kong. Winners are offered up to HK$ 5 million as research funding in five years. Another recipient of this award from CityU is Dr Chow Kwan Ting, Assistant Professor of the Department of Biomedical Sciences.