An alchemical symbol with the words ‘εν το παν’ (‘one is the all’) which inspired Kekulé in a dream to discover the structure of benzene.
Yujia Qing  

Yujia Qing: “The DCA gave me a unique opportunity to distill my abstract thoughts, which emerged during daily research, into a systematic plan.”

An interview with Yujia Qing (University of Oxford, UK), the winner of the Dream Chemistry Award 2019 with the project “Sequencing Life”.

What was the impulse that brought you to biochemistry?
I was trained as a chemist during my undergraduate studies and later moved on to pharmacology for a master’s degree and chemical biology for my PhD. However, strictly speaking, I am researching on single-molecule chemistry through a biophysical approach. I think it is the interdisciplinary training that eventually led me to an interdisciplinary research theme, which I would call a natural course, and not an impulse.

How was preparing your Dream Chemistry Award project different from your day-to-day research work? Do you feel it gave you anything else than the prize?
Absolutely. In shaping the proposal for the DCA, I got to take a step back and review my research from a distance. It is different from my day-to-day work as I needed to focus on the big picture rather than a specific experimental question. The Dream Chemistry Award gave me a unique opportunity to distill my abstract thoughts, which emerged during daily research, into a systematic plan. This is invaluable as a guide to my future research, even more so than the generous prize money.

Your project dealt with massively parallel single-molecule biopolymer sequencing. How did you come up with it?
I would say the big dream of a massively parallel single-molecule sequencer for biopolymers is always there in the field. I never set out to achieve such an ambitious goal as there were no clear paths towards it. Instead, I started off by investigating chemical reactions of interest at the single-molecule level, which serendipitously provided a potential design for the dream. To be more specific, in studying a specific chemical reaction known as the thiol-disulfide interchange, I established control over its regioselectivity and further exploited it to construct a mobile molecule, termed as the molecular hopper. Our hopper steps directionally on a track of multiple cysteine residues through consecutive regioselective thiol-disulfide interchange while carrying an oligonucleotide cargo. The chemical ratcheting motion exhibited by the hopper is analogous to the enzymatic ratcheting underpinning the nanopore sequencing technology. The step size is comparable to the contour length of individual building blocks in the information-rich biopolymers, such as DNA, RNA, and protein. The simple design of the hopper and its remarkable performance led us to dream that one day, millions of hoppers can work simultaneously on a surface to ratchet diverse individual biopolymers through single-molecule detectors for sequence identification.

How does the research you do and your chemistry dream relate?
My research mainly looks at chemical reactions at the single-molecule level. It is rooted more in basic science as I am curious about how chemistry works between individual molecules and how we can manipulate chemistry in a confinement. My dream, on the other hand, is more application-oriented with the ultimate goal to develop a new generation of biopolymer sequencers. However, I am a firm believer that discoveries made while researching on basic science will pave the way towards new technology. Hopefully, my single-molecule chemistry research will keep inspiring my chemistry dream till it is realised.

How important do you think is imagination and the ability to dream for a scientist?
For scientific research, imagination is the ability to come up with creative solutions to identified problems, often through integrating different research strategies and methods into a research plan. On the other hand, a scientist with the ability to dream has constant motivation to solve the big problems. Therefore, they are very important, if not necessary, for every scientist who aims to push the boundaries of science.

Unlike the other members of the DCA Top 5, you don't run your own research group yet. Is your dream chemistry project what you will pursue once such time comes?
Yes, it is what I would like to pursue once the time comes. One thing I like about my dream chemistry project is that it encompasses many fundamentally interesting questions and all of them come together for a big goal of new technology. I think the first step will be to address the individual basic science questions, such as if we can establish a proof-of-concept for protein sequencing or if we can generate surfaces that allow our chemical machine to move stepwise for a long distance.

How did you enjoy your stay in Prague?
It was absolutely delightful. Prague is a historic city with a vibrant culture, which I believe is necessary to foster the dreaming character of a scientist. As a first-time visitor to Prague, I am also lucky to have experienced the scientific side of this beautiful city by visiting IOCB. I am very impressed by the world-class academics and facilities in the institute and I look forward to future interactions with the brilliant scientists there.

Is there anything else you would like to tell us?
I would like to take the chance to thank my supervisor, Prof. Hagan Bayley. I am very fortunate to have been working with someone who dared to dream big decades ago and now his dream of nanopore sequencing has come true. This really encouraged me to draw up a dream of my own and work with belief to realise it one day.

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