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Professor Dek Woolfson

Why don’t crabs dissolve in the sea?

Synthetic Biology is a pioneering branch of science pushing at the boundaries of what we currently understand about the building blocks of life and how this knowledge can be used and manipulated to engineer new biological parts and devices. It crosses discipline boundaries forging what are sometimes unlikely collaborations between physicists, biologists, chemical engineers, social scientist, and others.

“There is potential impact of our research, but it is near impossible to predict what it will be, particularly as we are doing basic research, and specifically de novo design of proteins. Because it is basic research some of our ideas don’t work and some of our major discoveries happen by chance, but it still adds to the sum total of human knowledge,” explains Professor Dek Woolfson, who leads the Protein Design Lab at the University of Bristol. “Our pathways to impact are very much focused on building research capacity by encouraging the next generation of researchers in the area, helping to lay firm foundations for better engineering of biology, and also, engaging with the public. Synthetic biology is a new approach to the biological sciences and it will inevitably have its detractors. It is part of our job as the scientist doing it to explain to people what we are doing, to listen to their ideas, and to be responsive to their concerns.”Professor Woolfson’s research is concerned with understanding how biology builds functional structures using molecular building blocks, specifically proteins and other biological macromolecules. He has three current BBSRC-funded research projects in the area, the first is to create a toolkit of de novo designed peptides that could be used as building blocks in synthetic biology; the second is to use some of these to generate synthetic mimics of the extracellular matrix; and the third is to explore the possibilities of a new type of protein structure that his group has discovered, called CC-Hex.

The work on synthetic extracellular matrix has potential applications in tissue engineering to help generate tissues (skin, nerves, cartilage, bone etc) in the test tube. Professor Woolfson is currently working with clinical scientists exploring applications for the technology in wound repair.

The research project with CC-Hex is attempting to use rational protein design to turn the water-soluble protein structure into a membrane-spanning protein, and then to provide a basis for engineering new ion-channel proteins. If the team is successful they could possibly produce new molecules with potential application in water-purification and desalination devices; particularly small scale products that could be used easily in homes in the developing world without access to clean water.

Professor Woolfson is pursuing this early stage research in collaboration with the University of Oxford and with an Australian water consortium that brings together a team of engineers, biochemists, chemists, materials scientist, and microbiologists. The potential of hexaporins as components of water-purification systems will be explored by the University of Bristol and the Australian Commonwealth Scientific and Industrial Research Organisation (CSIRO). The hexaporins might have commercial and humanitarian applications, and these will be considered by the University of Bristol and the other partners in any future intellectual property, spin-out, licensing and review-sharing activities and agreements.

For both of these research projects, Professor Woolfson points out that it was curiosity not the end application that drove the discoveries. Thinking about real-world applications came after serendipitous findings.

“The truth is that most fundamental science researchers don’t tend to think about application from the start: they will often discover or invent things that have no immediate or apparent use. There is usually an ‘eureka’ moment or a chance meeting with colleagues that helps to reveal the potential application, which is often with someone external to the research or who has a different knowledge base or expertise,” explains Professor Woolfson

“When we discovered CC-Hex we thought we might use it to make enzymes. It was a visiting colleague from Australia who recognised the similarity of the structure to aquaporins (a natural protein that rescues water in kidneys, the brain, and even the roots of plants). He suggested that we explore that direction too and it is now the basis of our latest BBSRC grant. We are far from achieving a working prototype but are collaborating with Australian scientists with this goal in mind.”

Public engagement also helps Professor Woolfson to think about the possible real-world applications of his research. He and his team are very active taking the opportunity to talk about synthetic biology in various settings: in schools; at public lectures organised by universities, research councils, and learned societies; and at science cafés and similar public events. Professor Woolfson is particularly fond of the informal settings of science cafés.

“Regarding synthetic biology, mostly the feedback has been encouraging and positive, but you can get mixed feedback; some people can be critical feeling that we are playing God. You have to always expect the unexpected in terms of questions. Once, after making an off-the-cuff comment about biomaterials, which I illustrated by saying that crab shells were made from sugars, I was asked ‘why don’t crabs dissolve in the sea?’ That took me into explaining polymers and how one chemistry or property can be transformed into others through polymerisation. You are also likely to get ideas of what you might do in the lab as other people’s slightly different perspectives make you think differently.

“Public engagement forces you to really understand your science from different perspectives: you have to forget all of the jargon and break it down to explain exactly what is going on. It is the same skill that you need to teach undergraduates but even more so at the public interface. I find that being forced to think in this way has a positive impact on how I think about my own research,” he explains

He points out that public engagement is a good skill to encourage the younger members of the team to acquire. The Synthetic Components Network, of which the Professor Woolfson Lab is part, has provided public engagement training to young scientists. “As well as building research capacity in what we do, it is important to ensure that the next generation of scientists is comfortable with public engagement and understand the benefits,” he says.

Professor Woolfson’s advice to a basic scientist approaching their first Pathways to Impact is not to leave that section to the last minute and pay attention to the guidance, using headings and sub-headings to help structure the section, and initiate its writing.

“Pathways to Impact are not just about translating your work into some technology; that would put a stop to much fundamental science. Remember, you are not being asked to predict applications of your research per se, although that’s a valid impact of course, but to explain what you intend to do to disseminate your discoveries, whatever they might be. Collaboration, knowledge exchange, public engagement are all valid impacts, and routes to delivering these can and should be included in pathways to impact.”

Institution:University of Bristol
Funding council:BBSRC

Links
Summary synthetic biology by the Synthetic Biology Network
Dek Woolfson’s page