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Reporter speaks to Professors Paul Freemont (Life Sciences) andRichard Kitney (Bioengineering), who lead the EPSRC Centre for Synthetic Biology and Innovation (CSynBI) at Imperial, to learn what synthetic biology is and how Imperial is leading the way in using engineering and biological principles to systematically design new biological devices and systems.
Reporter speaks to Professors Paul Freemont (Life Sciences) andRichard Kitney (Bioengineering), who lead the EPSRC Centre for Synthetic Biology and Innovation (CSynBI) at Imperial, to learn what synthetic biology is and how Imperial is leading the way in using engineering and biological principles to systematically design new biological devices and systems.
The field of synthetic biology has been developing rapidly since the early 2000s, when the human genome was first sequenced. Paul (pictured below left) and Richard (below right right) became interested in the potential that this offered for building biological devices and systems from scratch and, in 2003, heard from colleagues at Massachusetts Institute of Technology (MIT) that similar work had started under the title ‘synthetic biology’. Paul explains: “With our incredibly strong engineering and life sciences departments at Imperial, we knew we had the potential to have a huge impact on the field and were excited that it would provide incredible opportunities for our students.”
In synthetic biology, bacterial DNA is modified according to the function you want the cell to perform. The DNA is then placed in a host cell to make a biological device that responds according to its engineered design. The ultimate aim of synthetic biology is to turn cells into programmable factories that can manufacture a wide range of products. These already include biofuels, leading to environmental benefits, and medical devices that save lives. “We believe we are on the cusp of a new revolution whose impact could be similar to the industrial revolution of the nineteenth century,” says Richard.
Traditionally, if scientists wanted a gene from an organism for research purposes, they had to grow the organism, extract its DNA, use polymerase chain reaction to copy the gene in huge quantities, then insert it into some carrier DNA and place it in the desired host cells.
Today, gene synthesis companies use the principle of synthetic biology to reduce the time and effort required for this process, by providing DNA sequences to scientists to order.
At Imperial, synthetic biology has been gathering increased momentum since April 2010, when Richard and Paul set up CSynBI with just seven researchers and their PhD students. Today the Centre brings together over 60 researchers from the Departments of Life Sciences and Bioengineering, in addition to social scientists and ethicists from the London School of Economics and Political Science (LSE). The Centre also collaborates with smaller groups at the Universities of Cambridge, Newcastle and Edinburgh.
One of the key research areas in synthetic biology is the creation of biosensors – detection devices that can be used in the manufacturing and healthcare industries. Paul describes one of CSynBI’s current projects, which he is leading: the development of a biosensor to prevent elderly people with urinary catheters from developing a severe bacterial infection. Catheter infections are normally caused by a build-up of bacteria on the outside of the catheter where they congregate into a pathogenic colony and spread up inside the device. The resulting infection in the bladder can lead to a high fever, that can be particularly serious for elderly patients. Under Paul and Richard’s supervision, a team of undergraduates designed a simple biological sensing device that, when applied to the outside of a hospital catheter, glows red to alert doctors to earlystage infection. This basic design has now been developed so that it can, with small modifications, be used to detect other bacterial infections.
Lecturer Dr Karen Polizzi (Life Sciences) is another researcher working on biosensors within the Centre. Her team is using synthetic biology to understand how to optimise the metabolism of cells that fight cancer, using biosensors to monitor the cell’s progress. “The biosensors are really useful because they give us a window into what is going on inside the cell and help us to detect any changes early on,” she explains. Karen says she enjoys working in synthetic biology, as it feels like anything is possible. “There is so much potential to revolutionise biobased manufacturing, to develop new therapeutics, to solve a lot of ‘grand challenges’, and to do it quickly, which is really important. Traditional biology might eventually get there, but synthetic biology will be able to do it faster,” she adds.
Another strand of synthetic biology research underway at the Centre involves translating electronic engineering principles to biology, to develop biological logic gates. Led by Richard, the team, including Dr Baojun Wang (Bioengineering) and Professor Martin Buck (Life Sciences), last year successfully demonstrated that they could build the biological equivalents of AND and NAND logic gates – the basic building blocks of computers and microprocessors. “Synthetic biologists can now begin to develop the biological equivalents of electronic digital devices – biological versions for biological applications,” Richard explains. Although still a long way off, he suggests that these biological logic gates could one day be used as the foundations of microscopic biological computers. Applications could include sensors that detect and destroy cancer cells inside the body, or which swim inside arteries, detecting the build-up of harmful plaque and rapidly delivering medications to the affected zone. The principles could be used in pollution monitors that can be deployed in the environment, detecting and neutralising dangerous toxins like arsenic.
Working alongside the Imperial scientists and engineers who are pioneering the field of synthetic biology is a team of societal and ethical researchers from the LSE. This partnership between traditional and social science means that the ethics of manipulating biological cells is considered at every step, ensuring that any concerns about the risks of releasing genetically altered material or bioterrorism are minimised. “The LSE team consider how to make the discipline environmentally and socially acceptable, and work out how we can modify the design to overcome any issues or risks from the beginning,” Paul says.
As a new field, synthetic biology offers students unique opportunities to contribute to cutting-edge research and the final year optional module for biochemistry, biomedical engineering and biology students is run by Paul and Richard, with colleagues in CSynBI. “Synthetic biology is a field driven by students,” muses Paul.
“It’s very unusual to have a field with so much energy and youth behind it. I think it appeals to students as it really allows them to be creative.” Postgraduate student, James Field (Bioengineering) says: “I have always found living systems breathtaking but before taking the synthetic biology module, I never truly appreciated the extent to which they can be re- engineered to solve realworld problems.” He describes how the students were plunged into a brave new world in which the lecturers challenged them to pick a problem and design a biological machine to solve it. “The next few weeks were spent stitching nature’s DNA into devices and computationally modelling their performance,” he says.
One of the activities that draws students to Paul and Richard’s module is the chance to get involved in the annual International Genetically Engineered Machine (iGEM) competition, held at MIT in the USA, in which thousands of undergraduates from across the world attempt to build biological devices and systems from standard DNA parts and operate them in living cells. Imperial has an outstanding record of winning the top prizes each year. After competing in the iGEM project, many of the students remain in the synthetic biology community, going on to do MPhils and PhDs.
Paul and Richard hope the CSynBI will be at the heart of the synthetic biology revolution, as more and more researchers start applying the techniques and recognising its immense potential. There is clearly a lot of buzz around the field and, as James says: “If I have learnt anything, it’s that the potential of synthetic biology is limited only by the human imagination.”
— Emily Ross-Joannou, Communications and Development
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