Faculty of Natural Sciences explores transforming science into innovation

Professor Sir Shankar Balasubramanian delivered this year's FoNS Dean's Annual Lecture

Professor Sir Shankar Balasubramanian delivers this year's lecture: “We could see a way to sequence the scale of a human genome in a matter of days.”

Chemist and co-inventor of the leading next-generation DNA sequencing methodology, Professor Sir Shankar Balasubramanian, highlighted the importance of basic science research funding to future innovation in industry and technology.

Speaking at this years’ Dean’s Annual Lecture, he spoke about his own experience translating his DNA replication research into a cutting-edge sequencing technology, which has been used to study the genetic origins of disease and track emerging virus strains during the COVID pandemic. 

Professor Balasubramanian is currently the Herschel Smith Professor of Medicinal Chemistry at the University of Cambridge and co-invented Solexa sequencing, a technology that was acquired by biotechnology giant Illumina for £600M in 2007 and that continues underpins large research initiatives such as the International Cancer Genome Project.

Starting from basic science

It became clear to us that we should pursue this because it would really be transformative... Professor Sir Shankar Balasubramanian Herchel Smith Professor of Medicinal Chemistry at the University of Cambridge

Professor Balasubramanian says his story started in 1995, near the start of his academic career in Cambridge, when his research group submitted a research proposal to observe a biological machine in action: a DNA polymerase. This machine, he explained, is responsible for copying an entire genome – which comprises of over three billion base pairs in a human – every time a cell divides.

DNA is composed of the iconic double helix structure, first imaged by Rosalind Franklin in 1953 and then studied by James Watson and Francis Crick. The letters used to write our genome are called ‘nucleotides’, molecules that bind in pairs to form the rungs that run along the entire helix. Adenine (A) always pairs with thymine (T), and cytosine (C) always pairs with guanine (G). 

Together, these four chemicals code instructions to create the building blocks of life in our bodies: proteins, enzymes and more. Each cell contains a copy of these instructions.

To create a copy, the DNA’s double helix structure is unwound into separate strands, each strand containing only one half of a ladder rung, one half of each base pair. These strands would form ‘templates’ upon which new DNA could be synthesised. Professor Balasubramanian’s group observed how a polymerase slowly built a new DNA strand using a template, matching each base with it corresponding pair one at a time.

Two years later, Professor Balasubramanian joined fellow chemist David Klenerman in a pub near to his office called the Pantom Arms, discussing the work happening down the road at the Sanger Institute. 

Both scientists were aware of the limitations of the then-prevailing method of Sanger sequencing, which was hitting a ceiling in cost and speed. Soon, the two realised the connection between Professor Balasubramanian’s basic science research and a groundbreaking new idea.

The polymerase that was duplicating DNA was also, in essence, reading it. It was how polymerases knew how to pair each nucleotide with a matching base pair.

Using polymerases modified with fluorescent dyes, scientists could see each nucleotide being added onto a growing strand of DNA, allowing them to sequence the entire genome. The reading process could be sped up even more by splitting the entire genome into fragments, and then reading different fragments in parallel.

The two scientists took their idea to the Sanger Institute and went on to found Solexa in 1998: “It became clear to us that we should pursue this because it would really be transformative if we could make it work so we had a lot of discussions over many weeks to formulate how we going to take this idea forward.”

Turning an idea into reality

Professor Balasubramanian joined a panel to discuss the future of innovation within academic research spaces, moderated by Professor Oscar Ces, Head of Department of Chemistry at Imperial College London. 

The panel included: Sir Mark Walport, Chief Executive of UK Research and Innovation; Dr Malcolm Weir, former CEO of Heptares Therapeutics Ltd; Sarah Haywood, Managing Director at Advanced Oxford; and Richard Broyd, an Advisory Director of Blenheim Chalcot and Chairman of Brightcure, a biotechnology start-up based in Imperial’s White City campus. 

The panel discussed how to unlock the potential of UK university spinouts. Professor Balasubramanian urged policymakers to continue funding academic research in the long-term.

“Unless we strongly fund basic science, innovation is dead a few years down the line… I don’t think this is not fully understood by some of the decision-makers. Everything I’ve just described would not have happened if we didn’t get the basic science funding at the beginning," he said.

No “magic bullet” to university innovation

Sir Walport added that there is no “single magic bullet”, stating the need to not only have an incubator space, like the one within Imperial, but also resources that can scale-up spinouts once they hit a certain size.

Affordable spaces for expansion as well as a ready supply of labour were critical, he said: “The skills that you need in the laboratory to discover things are not entirely the same skills as you need to create companies, and particularly to grow them.

Dr Chiara Heide, who completed her PhD at Imperial and went on to found biotechnology company P.Happi, shared her own experiences with creating her start-up in an accelerator where her group encountered many challenges from taking their idea from a proof-of-concept stage to a marketable product. 

She pointed out some cultural differences in the start-up ecosystem in the US versus that in the UK and Europe: “When it comes to investment, I think often US investors [are] more open generally from conversations – we’re still early on, but I think [they’re open to] thinking about the bigger picture and the bigger idea, whereas in the UK and Europe, it's more about all the risks and the problems they see, which can be quite limiting.”

Whilst the UK may lack the angel investors present in the UK, Miss Haywood noted that the UK often was rich in the components required in the soft infrastructure needed for innovation.

She said, “I think this is one of the things that we don't shout about enough in the UK, is the willingness of people to engage and to help… [People] are giving advice and guidance and working to help boards to be successful. To the honest brokers in ecosystems, who can just connect and make introductions, those soft elements are incredibly important.”

Enterprise within Imperial 

Mr Broyd noted the significance of having many spin-outs located within a single cluster, using Imperial’s White City Innovation District as a key example. “What’s vital, I think, for startups is to identify clusters where you can locate because the advantage of clusters is that they enable venture smaller companies to operate at the scale that larger companies can by virtue of being in a cluster,” he said. 

The White City Innovation District was launched in 2022 by a partnership between Imperial and the London Borough of Hammersmith and Fulham. Serving as a global economic hub for science-driven innovation, Imperial hosts incubator facilities and laboratories for early-stage companies.

Six spin-outs located in White City and founded by former Imperial staff and alumni showcased at the lecture.

FreshCheck, a start-up developing colour-change tools for hygiene verification, was created by Imperial PhD alumni Dr John Simpson and Dr Alex Bond. Dr Bond said: “The ability to create spin-our companies like Solexa show how important fundamental science is. We'd also like to say that events like these have been crucial for us – from our first round of investment to getting real grounded feedback on our products is critical. Imperial's help and regular events have been crucial for our company's success.” 

RFC Power, a spinout developing novel approaches to sustainable battery design, was created by a research group in Imperial’s Department of Chemistry. “Imperial College has always encouraged the culture of working on research topics that can address environmental challenges. Events like this are fantastic opportunities to increase public exposure to start-ups' commitment and their impact in solving these problems,” said Dr Ashkan Kavei, the engineering lead at RFC Power.

The event was closed by Professor Richard Craster, Dean of the Faculty of Natural Sciences, who thanked Professor Balasubramanian as well as the panellists for such an informative and engaging discussion.

Image: Flickr/Kake