Winner 2025: Chemistry Biology Interface open Prize: Khorana Prize
Professor Sir Shankar Balasubramanian M番茄社区
University of Cambridge
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2025 Khorana Prize: awarded for groundbreaking and highly influential work on the chemistry and chemical biology of nucleic acids, which has transformed our understanding of quadruplex DNA.
DNA generally forms a two-stranded double helix, in which the four DNA building blocks link across the strands through specific hydrogen bonded base pairs 鈥� guanine (G) pairing with cytosine (C), and adenine (A) pairing with thymine (T). In addition to this well-known form, a distinct four-stranded secondary structure called a G-quadruplex can form in certain G-rich regions of DNA (or RNA).
In these structures, four guanine bases hydrogen-bond together in a planar arrangement known as a G-tetrad. For the past 27 years, Professor Balasubramanian's lab has focused on the chemistry, biological presence and functional significance of G-quadruplexes in human cells. These structures can form in genomic regions that regulate gene activity, suggesting they play a role in controlling whether genes are turned on or off.
The current view is that G-quadruplexes appear to represent a previously unrecognised mechanism for regulating gene expression and cellular states. G-quadruplex formation is often associated with genes that are highly active in cancer. Small, drug-like molecules that selectively bind to G-quadruplex structures have shown promising anticancer activity and have the potential to target a wide range of cancers without the extreme toxicities associated with standard chemotherapies.
Biography
Sir Shankar Balasubramanian is the Herchel Smith Professor of Medicinal Chemistry at the University of Cambridge and senior group leader at Cancer Research UK鈥檚 Cambridge Institute. He works on the chemistry, structure and function of nucleic acids. He is a co-inventor (with Sir David Klenerman) of the leading next generation DNA sequencing methodology, Solexa sequencing (now Illumina) that has made routine, accurate, low-cost sequencing of human genomes a reality and has revolutionised biology.
He also invented chemistry to decode several modified (epigenetic) DNA bases and DNA secondary structures (G-quadruplexes) in the genome, and has made seminal contributions towards the understanding of their dynamics and function. His work on small molecule recognition of nucleic acids has revealed molecular mechanisms that can be exploited to modulate the biology of cancer. His collective contributions span fundamental chemistry and its application to the biological and medical sciences. Sir Shankar was knighted in 2017 for his services to science and medicine.
He was awarded the Royal Medal with Sir David Klenerman (2018), the Millennium Technology Prize with Sir David Klenerman (2020), the Breakthrough Prize for Life Sciences with Sir David Klenerman and Pascal Mayer (2022), the Novo Nordisk Prize with Sir David Klenerman (2024) and the Canada Gairdner International Award with Sir David Klenerman and Pascal Mayer (2024).
Experimental research on complex problems benefits immensely from different viewpoints and methodological approaches. This is only possible through collaboration and teamwork.
Professor Sir Shankar Balasubramanian
Q&A with Professor Sir Shankar Balasubramanian
How did you first become interested in chemistry?
I was interested in all science at high school, then progressively more towards the structure and property of molecules as I entered university. Subsequently, I have focused on the relationship between molecules and biological function.
Tell us about somebody who has inspired or mentored you in your career
My primary school headteacher, Brian Leitch, picked up on and fostered a deep curiosity in me at a relatively early age through his teaching and thoughtful mentoring. I owe much to many who have mentored me throughout my education and academic career.
What motivates you?
The possibility of discovery, generating new understanding and creating methods to observe what could previously not be observed.
What has been a highlight for you (either personally or in your career)?
Mentoring PhD students and postdocs who have subsequently gone on to make scientific breakthroughs and become outstanding teachers as they built their independent scientific careers.
What does good research culture look like/mean to you?
An environment where researchers are passionate and driven by curiosity
Why do you think collaboration and teamwork are important in science?
Experimental research on complex problems benefits immensely from different viewpoints and methodological approaches. This is only possible through collaboration and teamwork.