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13 July 2012
In a series of articles we will be highlighting the work of some of the leading synthetic biology researchers in the UK. Here we profile Professor Dek Woolfson of the University of Bristol, Professor Jamie Davies of the University of Edinburgh and Professor Richard Cogdell of the University of Glasgow.
Flat pack proteins – Professor Dek Woolfson, University of Bristol
Professor Dek Woolfson is hoping to use synthetic biology to create new structures out of proteins with uses ranging from wound repair to water purification.
- Proteins play many important roles in nature.
- Proteins can assemble into complicated structures like tiny pumps and motors.
- Scientists are hoping to combine proteins in new ways using synthetic biology to create useful new tools for uses as diverse as water filtration and medicine.
Proteins are like nature's robots working tirelessly in the cells of every plant, animal and microbe to do virtually all of the important functions that make life tick. Each individual protein can twist and fold into an incredibly complex 3D shape, with holes, cracks and protrudances giving it its function. Groups of proteins then combine with one another and other types of molecules to create bigger and more complicated structures still. Understanding how proteins assemble and combine is at the heart of Professor Dek Woolfson's research at the University of Bristol.
Professor Dek Woolfson
This work is important for our understanding of biology because by figuring out how to make parts these molecular machines from scratch scientists can get a much better understanding of how they work in nature. It could also have a range of possible applications.
Professor Woolfson and his team are working on a toolkit of newly designed proteins that could be used as building blocks to produce biological machines. This is a key pillar of a synthetic biology approach. Scientists like Professor Woolfson hope to create catalogues of modular parts so that biological structures can be built from flat pack rather than being crafted from scratch each time.
One such structure that Professor Woolfson's team are working on is a synthetic version of the extracellular matrix, the scaffold that surrounds our cells.
A synthetic extracellular matrix could be used in regenerative medicine to help generate tissues like skin, nerves or bone in the test tube that could then be transplanted into patients. Professor Woolfson is currently working with clinical scientists exploring applications for the technology in wound repair.
Another project in their lab is attempting to use rational protein design to produce new technologies for water purification and desalination. The team have discovered a new cylindrical protein structure which they call CC-Hex which they think could be engineered into biological membranes to filter water. These devices would be particularly valuable for producing small scale products that could be used easily by people who do not have access to clean water in the developing world.
This research is being developed 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.
Prof Woolfson explains "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."
Designer tissues – Professor Jamie Davies, University of Edinburgh
Stem cells offer incredible medical promise because they can turn into virtually any tissue in our bodies; but what about tissues that do not exist in our bodies or even in nature?
- During development, a simple group of cells multiplies and rearranges to form complicated tissues and organs and eventually a whole plant or animal.
- Currently, scientists are working to coax stem cells to produce human tissues in the lab to repair damaged organs.
- Using synthetic biology, scientists could put new programming in to cells so that they develop into never-before seen types of tissues with a range of medical uses.
Professor Jamie Davies of the University of Edinburgh is working to use synthetic biology to control cell and tissue shape, research which he calls 'synthetic morphology'. His work could lead to a future where cells can be programmed to self assemble into new structures and tissues which have never existed before in nature.
Professor Jamie Davies
This science is in its infancy and there are a number of technical hurdles still to be overcome. However it promises to give us a far greater understanding of how organisms develop which might give scientists insights that could help prevent developmental abnormalities like conjoined twinning.
As well as increasing our understanding of development this work could allow the production of useful new tissues that would not be possible with stem cells. You could imagine, for example, that tissues grown in this way could provide an interface to allow a person to control movement in an artificial hand or even to see through an artificial eye.
These developments are still some way off. However in the nearer term Professor Davies hopes to be able to improve medical technologies like dialysis machines by developing tissues that can live happily inside medical machinery. Dialysis machines are very good at replicating the mechanical functions of a kidney but they cannot perform the biochemical functions that are important in properly filtering blood. By designing tissues that could grow along the tubes of a dialysis machine researchers could produce a more effective artificial kidney.
Professor Davies explains "The development of even really complex tissues can be broken down into a series of simple events like the multiplication, clumping together or movement of cells. There are about ten of these simple behaviours and we think that by programming cell circuitry to carry them out in different orders we can coax cells into new types of tissues in ways that we can predict."
The immediate value of this work to scientists is that it will give them a much deeper understanding of the process of development. How relatively unorganised populations of cells assemble precisely into something as complex as a person is one of the big outstanding questions in biology. By developing synthetic systems that cause cells to organise and assemble themselves, the researchers can begin to understand how it happens in nature.
One of the immediate challenges that Professor Davies and their team faced when starting this work was that they wanted to work with animal cells. Most synthetic biology to date has been in simple organisms that are easy to work with like bacteria or yeast. Mammalian cells are much bigger and more complex than those of bacteria which make them considerably harder to work with.
However this work is not just limited to human or animal cells. It should be possible to programme bacteria, yeast or plant cells to form new multicellular structures which could have an enormous range of uses in medicine and industry.
The artificial 'leaf' – Professor Richard Cogdell, University of Glasgow
Professor Richard Cogdell is hoping to use synthetic biology to create an artificial "leaf" capable of converting the sun's energy into sustainable liquid fuels.
- Plants use photosynthetisis to capture energy of the sun to create fuel to power the plant's growth.
- We use this fuel ourselves in the form of wood, coal, oil and gas.
- By using the tools of synthetics biology, scientists hope to create an artificial system that can do photosynthesis,
- This could capture the sun's energy like a solar panel but would produce liquid fuel rather than electricity.
We have always relied on plants to provide us with energy. For millennia, burning wood was humanity's main, sometimes only, source of power. Later, more energy dense fuels – coal, oil and gas, drove the development of modern society.
Professor Richard Cogdell
By burning these fuels we are tapping into the stored energy of the sun. In the case of wood this might have been captured months or years before. When we burn fossil fuels we are releasing energy that fell as sunlight on the world of the dinosaurs hundreds of millions of years ago.
Only plants, algae and some bacteria have the amazing ability to capture and store the sun's rays as sugars using photosynthesis. While amazing, photosynthesis is actually quite an inefficient process. A plant is not a machine for producing fuel, rather a machine for producing plants, and as such scientists think that they might be able to tweak photosynthesis to produce fuel more efficiently. The researchers, based at the University of Glasgow, hope to deliver the next stage in our long relationship with photosynthesis by taking it out of the leaf and into the lab.
Professor Cogdell, who is leading the research project, explains: "More energy hits the surface of the Earth in the form of sunlight in the space of one hour than the entire human race uses in a whole year. This abundant energy is given away for free but making use of it is tricky. We can use solar panels to make electricity but it's intermittent and difficult to store. You can't fly an aeroplane or send a ship round the world using batteries, you need a fuel. What we are trying to do is to take the energy from the sun and trap it so that it can be used when it is needed most."
The researchers hope to use a chemical reaction similar to photosynthesis but in an artificial system. Plants take solar energy, concentrate it and use it to split apart water into hydrogen and oxygen. The oxygen is released and the energy from the hydrogen used to lock carbon into a fuel. The latest research aims to use synthetic biology to replicate the process outside of the cell.
Professor Cogdell added: "We are working to devise a chemical system that could replicate photosynthesis artificially on a grand scale. This artificial leaf would use solar collectors and produce a fuel, as opposed to electricity."
Professor Cogdell hopes that his team's artificial system could also improve on natural photosynthesis to make better use of the sun's energy. By stripping back photosynthesis to a level of basic reactions, much higher levels of energy conversion could be possible.
Ultimately, success in this research could allow the development of a sustainable carbon neutral economy arresting the increasing carbon dioxide levels in the atmosphere from fossil fuel burning. In fact, if successful, this research could allow for carbon to be harvested from the atmosphere and returned to the ground, reversing the accumulation of carbon caused by burning fossil fuels.
The research is funded through a joint EU funding scheme "EuroSolarFuels" which aims to produce fuels from light. The BBSRC funds the UK part of this research.
What is synthetic biology?
Synthetic biology is the science of designing, engineering and building useful new biological systems which have not existed before in nature.
Using our ever-increasing understanding of genetics and cell biology synthetic biologists are able to design complicated biological parts, systems and devices to act as sensors, tissues or to produce useful chemicals. These technologies could deliver advances in a wide range of fields including medicine, biofuels and renewable materials.
A synthetic biology approach offers incredible promise but also poses many ethical, legal and even existential questions for the scientific community, policymakers and for all of us to think about. Some of these questions were explored in a public dialogue carried out by BBSRC and the Engineering and Physical Sciences Research Council in 2010.