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Synthetic biology in the real world: Case studies

Posted on 25/02/2016

The wide-ranging applications of synthetic biology will play an important role in growing the UK's bioeconomy.

New synthetic biology technologies are starting to offer exciting opportunities across a range of industries including manufacturing, pharmaceuticals, biofuels and health.

Research Council funding in collaboration with a wide variety of national and international partners across academia and industry, is supporting the long-term growth of UK synthetic biology, development of a highly skilled workforce and an infrastructure to underpin and enable cutting edge research in industry and academia, as well as providing support for synthetic biology start-up companies.

The pervasive potential of synthetic biology is brought to life below through a series of case studies ranging from a biosensor toolkit with the ability to treat chronic conditions such as diabetes through to using enzymes from yeast mould to unlock cleaner routes to producing biofuel.

Detection of food spoilage organisms using bionanotechnology

Food spoilage post harvest represent a significant issue in the food production industry. For example it is estimated that in potato production a large processing house can loose over £100,000 purely from soft potato rot. A key part of addressing this issue is the development of new rapid test systems that can identify sources of microbial contamination in incoming vegetables and hence prevent spread within the facility.

Researchers in Professor Tim Dafforn’s laboratory at the University of Birmingham have established a diagnostics spinout company, Linear Diagnostics Ltd, to develop a new rapid detection system. The method underpinning this system uses synthetic biology methods to engineer novel bionano particles that can report the presence of an infection to a handheld reader. The company was founded with an initial investment from bioscience ventures limited and has been developing the test as part of an Innovate UK funded project with the Food and Environment Research Agency (Fera) and members of the potato industry.

Investing in emerging leaders

The Synthetic Biology Leadership Excellence Accelerator Program (SynBio LEAP) invests in the next generation of leaders in synthetic biology by providing the environment to learn skills for engaging a broad range of stakeholders in the development of the field with a strong ethical foundation for the future.

LEAP graduates have lead ventures such as the Synthetic Biology Standards Consortium that is driving interoperability and standards in bioengineering and SynBioBeta that showcases emerging industries, stimulating commercial investment.

With funding from the Knowledge Transfer Network and SynBiCite, six UK-based Fellows were among the twenty-three Fellows selected in 2015 on the basis of their visions and strategies to advance the responsible development of biotechnology in a global context.

‘Re-engineering cellular factories to make novel proteins not found in nature’

Professor Jason Chin’s research programme at the MRC Laboratory of Molecular Biology, Cambridge involves expanding the available repertoire of amino acids, the twenty building blocks that are strung together to make the proteins which carry out many of the processes that keep us alive. He is working on re-engineering the cellular factories that normally make proteins in a cell, to get them to make proteins containing entirely new amino acids that are not found in nature.

This provides a powerful approach for seeing what proteins get up to in a cell, tracking them rather like with the GPS on our phones to find out where they go, and which other proteins in the cell they talk to. By introducing new chemical groups into proteins, such synthetic biology approaches can help us understand and image cellular processes in unprecedented detail, and can take us a step closer to providing new molecules and therapeutics to tackle disease.

‘World’s first artificial enzymes created using synthetic biology’

Professor Philipp Holliger’s (MRC Laboratory of Molecular Biology, Cambridge) team have created the world’s first enzymes – ‘XNAzymes’ – made from artificial genetic material not found anywhere in nature.

Building on previous work in which they created ‘XNAs’ (synthetic versions of the naturally occurring DNA / RNA molecules), their ‘XNAzymes’ are capable of cutting up or stitching together small chunks of RNA, just like naturally occurring enzymes. They also discovered an XNAzyme that can stitch together short strands of XNA, a reaction that is not found in nature.

The research gives new insights into the origins of life, namely that there are a number of possible alternatives to nature’s molecules that will support both the genetic and catalytic processes required for life. Because their XNAzymes are much more stable than naturally occurring enzymes, this synthetic biology approach could provide a starting point for an entirely new generation of drugs and diagnostics for a range of diseases, particularly useful in developing new therapies against cancers and viral infections which exploit the body’s natural processes to take hold in the body.

Organoids – animal free drug testing

The UK is continually trying to reduce the use of animal testing in research, both for ethical reasons and because there are limits in the usefulness of animal-based data in predicting human safety. New testing methods, based on growing human tissues and organs in culture, might provide a much more effective and ethical alternative to animal tests.

The Jamie Davies laboratory at the University of Edinburgh is pioneering the application of the techniques of synthetic biology to the artificial control of cell shapes, cell associations and ultimately the formation of artificial tissues. This field is ‘synthetic morphology’. At present, they are at the first stage of this work: they have produced a library of molecules that can be controlled by existing synthetic genetic circuits and that result in cells undergoing one the basic events by which most biological shape is formed. They have also produced synthetic patterning systems that have the potential to organise synthetic tissues automatically.

Creative ways of generating dialogue around synbio

The Synthetic Aesthetics project paired six artists/designers with six scientists/engineers. The aim of the project was not to beautify or better communicate the science, but to explore the intersection of art, design, and synthetic biology in a way that allowed for dialogue and critique.

The collaborations involved a diverse range of activities including: extracting the logic of biology and applying it to architecture, sonifying amino acids, integrating ‘design thinking’ into synthetic biology, making cheese from bacteria that grow on human skin, and re-interpreting synthetic biology from the humbling perspective of geological time.

The project showed that involving artists and designers in synthetic biology can provoke reflection about the social, political and economic complexity of the technology. Their work can help us find new languages and metaphors, and can articulate a wider range of objectives, pathways and outcomes than would be envisaged otherwise.

Synbio health impact for developing countries

Arsenic in drinking water is an enormous public health issue in Bangladesh, West Bengal, Nepal and other areas of South Asia, with more than 100 million people at risk. Tens of millions of wells requiring periodic retesting, many in remote rural areas, current tests are expensive and unreliable.

Researchers at Cambridge and Edinburgh universities, funded by the Welcome Trust, have formed a consortium to develop a whole cell biosensor for detection of arsenic. The system shows high sensitivity and specificity and can easily detect arsenic at the 10 ppb WHO limit, results can be shared via a mobile phone app.

The consortium has undertaken extensive consultation with government organisations, NGOs and local people in Nepal and Bangladesh to ensure that the system meets stakeholder needs. The biosensor organism has been submitted to EU authorities as a test case for regulation; if successful, this will be the first chassis organism approved for use outside a laboratory under this legislation, and will open many new possibilities for other applications in synthetic biology.

YeastFab offers useful tools for industrial biotech

Dr Patrick Cai, Principal Investigator at the University of Edinburgh’s Centre for Synthetic and Systems Biology (SynthSys) and co-director of the Edinburgh Genome Foundry, along with collaborators from Tsinghua University have published their first paper on construction of YeastFab – a library of well characterised yeast genetic parts that will serve to expedite metabolic engineering of this industrial workhorse.

It is a routine task in metabolic engineering to introduce multicomponent pathways into a heterologous host for production of metabolites. However, this process is laborious taking weeks to months due to the lack of standardised genetic tools. Highly efficient protocols (termed YeastFab Assembly) have been developed to synthesise genetic elements as standardised biological parts, which can then be used to assemble entire metabolic pathways in simple steps.

The team proved that their strategy worked by reconstructing the metabolic pathway that produces carotene (Vitamin A) in a matter of days, rather than weeks using more traditional methods.

Synpromics – the power of synthetic promoters

Synpromics was founded by Dr Michael Roberts in 2010; it develops synthetic promoters which can specifically regulate gene expression. Promoters are a key element in expressing synthetic genes and need to be modified depending on the organism and product; current promoters are limited and inadequate for current needs.

In a recent Innovate UK funded grant, Synpromics worked with the University of Edinburgh’s Centre for Synthetic and Systems Biology (SynthSys) to create a panel of gene promoters that could increase productivity of biopharmaceutical production in mammalian CHO cells. This was a success with several candidates driving protein expression some 10-fold higher than the industry standard CMV promoter.

Synpromics is now discussing license terms with several multi-nationals within the Bioprocessing sector in order to evaluate the efficiency of selected synthetic promoters in an industrial setting and it is expected that these promoters will be effectively used to improve production of a vast range of biologics. Synpromics has recently raised over £2.1 million of new funding which it will use for business expansion and further development of its technology.

Standards for engineering in plants

The introduction of standards for the assembly of characterised DNA sequences and the establishment of a Registry of Standard Parts were landmarks in microbial engineering. Improvements in the ability to reprogram plants will impact a wide range of industries including textiles, fuels, sugars, fine chemicals, drugs and food.

Researchers at the OpenPlant SBRC (University of Cambridge, John Innes Centre and The Sainsbury Laboratory) have established a common genetic syntax that enables the exchange of standard DNA parts for plants and other eukaryotes. This standard has been ratified by an international consortium of scientists and is being applied to the production of parts for genome editing, the engineering of novel traits and to enable coordinated development of supporting hardware and software for bioengineering. The standard has also provided a route for the deposition of plant parts at the Registry of Biological Parts and the establishment of an inaugural plant track at in the 2016 iGEM competition.

Plants as bio-factories

The CPMV-HT (Cowpea Mosaic Virus-HyperTranslatable) expression system, developed by Prof George Lomonossoff and Dr Frank Sainsbury at the John Innes Centre, has established a unique position for the UK for rapid transient expression of proteins in plants.

The technology is extremely powerful and was used under licence by the Canadian company Medicago to produce 10m effective doses of H1N1 (swine flu) VLP Vaccine in just 30 days, while the traditional route would have taken 9 – 12 months.

Taking a synthetic biology approach, researchers at the OpenPlant SBRC (University of Cambridge, John Innes Centre and The Sainsbury Laboratory) are finding the CPMV-HT technology highly amenable for expression of plant natural product biosynthetic pathways for the production of high-value chemicals.

Boosting bioactives
Tomatoes are proving to be a great system for production of bioactive compounds that offer protection against e.g. inflammation, cancer and cardiovascular diseases.

Part of the OpenPlant SBRC, Professor Cathie Martin’s group at the John Innes Centre have taken a synthetic biology approach to introduce new metabolic pathways into the fruit of tomatoes, for example to produce resveratrol, a health-promoting compound normally found in red wineThe result: one large 100g tomato contains the same amount of resveratrol as 27 bottles of Pinot Noir. These varieties are already being used to develop skin care products in collaboration with Essex company Biodeb.

Engineering Nitrogen Symbiosis for Africa (ENSA)

During the Green Revolution nitrogen fertilisers as much as tripled cereal yields in some areas. However, these synthetic fertilisers remain unaffordable in developing countries, for example for smallholder farmers in sub-Saharan Africa whose yields are 15% to 20% of their potential.

As part of the Engineering Nitrogen Symbiosis for Africa (ENSA) project, Professor Giles Oldroyd’s group at the John Innes Centre is taking a synthetic biology approach to engineer nitrogen-fixation into cereals. Legumes are able to form symbiotic interactions with nitrogen-fixing rhizobial bacteria through formation of root nodules.

Engineering this complex interaction into cereals is highly ambitious and could not be tackled without the tools of synthetic biology. The potential impact on yields in sub-Saharan Africa without reliance on chemical fertilisers is huge.

Mould unlocks new route to biofuels

Scientists at The University of Manchester have made important discoveries that form the basis for the development of new applications in biofuels and sustainable manufacturing of chemicals. Researchers identified the exact mechanism and structure of two key enzymes isolated from yeast moulds that together provide a new, cleaner route to the production of hydrocarbons.

The team investigated the mechanism whereby common yeast mould can produce kerosene-like odours when grown on food containing the preservative sorbic acid. Using Diamond Light Source, the UK’s national synchrotron facility at Harwell, they were able to provide atomic level insights into this bio catalytic process, and revealed similarities with procedures commonly used in chemical synthesis but previously thought not to occur in nature. Research also focussed on the production of alpha-olefins; a high value, industrially crucial class of hydrocarbons that are key chemical intermediates in a variety of applications (e.g. synthetic lubricants, surfactant and detergents).

Scientists a step closer to developing renewable propane

Researchers at The University of Manchester have made a significant breakthrough in the development of synthetic pathways that will enable renewable biosynthesis of the gas propane.

This study provides new insight and understanding of the development of next-generation biofuels. Published in the journal Biotechnology for Biofuels, scientists at the University’s Manchester Institute of Biotechnology (MIB), working with colleagues at Imperial College London and University of Turku, have created a synthetic pathway for biosynthesis of the gas propane.

Their work brings scientists one step closer to the commercial production of renewable propane, a vital development as fossil fuels continue to dwindle.

Single-step fermentative production of the cholesterol-lowering drug pravastatin

University of Manchester researchers, together with industrial partner DSM, have developed a single-step fermentative method for the production of leading cholesterol-lowering drug, pravastatin.

Pravastatin is normally produced by stereoselective hydroxylation of the natural product compactin, this is an expensive process due to low yields.

The antibiotics producer Penicillium chrysogenum metabolic pathway was re-programmed to produce industrially relevant levels of pravastatin at a pilot production scale. This demonstrates the use of synthetic biology techniques to produce industrially relevant amounts of an important drug.

Enzymatic Menthol Production

Menthol isomers are high-value monoterpenoid commodity chemicals, produced naturally by mint plants. The high demand by the flavour and fragrance industries for natural sources has a high cost in terms of arable land use and expensive distillation and filtration processes, which means that alternative clean biosynthetic routes to these compounds are commercially attractive.

Researchers at the University of Manchester have engineered E. coli to efficiently convert pulegone (an essential oil produced by a variety of plants) to menthol. To achieve this they combined traditional pathway assembly techniques with classical biocatalysis methods to engineer and optimise the pathway in a “one-pot” approach.

Oxitec

Oxitec, a pioneering company founded in 2002 as a spinout from Oxford University funded by the BBSRC, has been sold to Intextron, a US based bio-technology company, for £102 million.

Oxitec has developed an innovative and environmentally friendly solution for controlling insect populations through the production of ‘sterile’, self-limiting insects whose offspring do not survive. Unlike conventional approaches to insect control using insecticides that can affect the broader ecosystem, Oxitec programmes are directed at a single species.

Intrexon Corporation intends to integrate its synthetic biology platform to advance Oxitec’s existing initiatives to combat diseases like dengue fever as well as to tackle agricultural pests that impact food supply worldwide.

Oxford Biotrans – sustainable grapefruit flavour

Oxford Biotrans is a spin-out company from Oxford University; its first process will produce nootkatone which gives grapefruit its flavour.

An alternative source of natural nootkatone is needed as extraction from grapefruit peel is difficult and the supply is limited, resulting in it being one of the most expensive flavour ingredients in the world (typically £2000 to £5000 per kg). Chemical synthesis of nootkatone is also not attractive as it is inefficient and often involves the use of toxic metals.

The key technology is a modified version of an enzyme Cytochrome P450, which was developed at the University of Oxford by Dr. Luet Lok Wong. To produce nootkatone, valencene (readily produced from orange oil) is converted to nootkatone using the enzyme P450.

The product has already created strong market interest and will be available in commercial quantities in the coming months. Oxford Biotrans has recently raised £2.5 million of new investment which it will use to establish its own laboratory and office facilities in Milton Park, Oxfordshire, recruit several additional employees (largely scientists and engineers) and thereby develop further novel processes using its patented P450 enzyme technology.

Synthace

Synthace’s purpose is universal bioscience productivity. Their deceptively simple bio-programming language, Antha is bioscience’s missing link.

Antha effortlessly spreads biological information in a repeatable way, easily linking laboratory equipment, protocols and processes to bring Design for Manufacturing to bioengineering.

The company works with international businesses such as Merck & Co. and Dow AgroSciences to develop high productivity bioprocess’s to make bio-based products, and with equipment vendors such as Gilson and CyBio to implement Antha software tools for automation.

By linking everything Antha allows vast and speedy optimization, enhancing productivity for any bioscience from pure research to volume manufacture.

Autolus – Genetically engineered cellular robots to attack cancer

Autolus is a spin out company from UCL based on the work of Dr Martin Pule. It is developing cancer therapies based on engineering immune cells (called CAR T- cells) to enable them to more effectively target cancer cells.

This technology will enable cancer to be specifically targeted, unlike current treatments which are indiscriminate and kill healthy cells as well as cancer cells.

Clinical trials have demonstrated the underlying technology to be effective, and a Company, Autolus Ltd, has been established by Syncona (a Wellcome Trust Investment Company) to further develop and commercialise next generation engineered T-cell therapies.

A sustainable source of omega-3?

The primary sources of omega-3 in humans is via the consumption of fish, however, fish do not produce omega-3 themselves, but accumulate it from the food they eat. Farmed fish are fed on fishmeal and fish-oil, which contain high levels of omega-3, however this is unsustainable and an alternative source of omega-3 is needed.

Researchers from Rothamsted have successfully engineered Camelina plants to produce omega-3. The plants recently tested in the field, and were shown to be stable and produce useful quantities of omega-3.

This provides hope for sustainable land-based sources of omega-3 fish oils, thereby releasing pressure from the oceans.

Importantly, this study represents the most complex piece of plant metabolic engineering to undergo environmental release and field-scale evaluation, a process which will be essential for any synthetic biology crops in the future.

iGEM – from student competition to spin-out company

The iGEM competition was started in 2004 and has since developed into a global competition with undergraduate and high school tracks. The competition involves using standard biological parts (BioBricks) to build genetically engineered systems. UK teams have consistently done well in iGEM, with Imperial coming 2nd overall in 2014.

Several start-up companies have been established using ideas originally conceived as UK iGEM projects such as; Bento-bioworks (UCL 2013) which is creating an all in one laboratory, Labgenius (Imperial 2014) which focuses on microbial expression optimisation, Morph Bioinformatics (UCL 2012) which focuses on genomics and bioinformatics and CustoMeM which is making customisable ultrafiltration membranes (Imperial 2014).

With several more projects developed further for example; an Arsenic biosensor which was awarded money from the Welcome Trust (Edinburgh 2006 and Cambridge 2009) and a cell-free TNT sensor (Exeter 2012) which was awarded money from DSTL. Finally GeneGuard (Imperial 2011) started off as an iGEM project and received further funding from DSTL and BBSRC to further develop it and is now influencing international GM regulations.

Antibiotic pathway engineering tools

Professors Marshall Stark and Maggie Smith from the University of Glasgow and the University of York are using phage integrases to facilitate the search for new antibiotics to combat antibiotic resistance.

Bacterial genomes contain many antibiotic biosynthesis pathways but we do not know in most cases whether their products are useful. The integrases can be used to assemble whole pathways or parts of pathways in an expression host to generate new compounds for bioactivity testing.

To demonstrate the use of the integrases they have reconstructed the pathway for erythromycin, a known antibiotic, in a Streptomyces expression host and shown how the reconstruction facilitates swapping in parts from other antibiotic pathways to generate a new antibiotic.

Sphere Fluidics

Sphere Fluidics Limited is an established Life Sciences Tool company based on Babraham Research Campus (UK). The company is focussing on developing single cell analysis systems for therapeutic discovery. This technology involves miniaturised biochips and is incredibly useful as it can screen several hundreds of thousands of samples per day by mass spectrometry (normal rates are 1-10,000 per day) and so speed up the Design-Build-Test cycle.

Sphere Fluidics has formed a collaboration with GlaxoSmithKline (GSK) to further develop this technology to detect advanced pharmaceutical ingredient production in engineered microbial libraries.

Sphere Fluidics has also received a joint Innovate UK grant with Dr Tom Ellis from Imperial College London to use this microfluidic technology to measure outputs from novel cells with sets of promoters and genes designed using synthetic biology.

Algal oils by design

Professor Johnathan Napier and Dr Olga Sayanova are leading the project on metabolic engineering of microalgae for the enhanced production of omega-3.

Omega-3 are long-chain fatty acids found in fish oils which are widely acknowledged to be beneficial components of the human diet.

They have engineered the diatom Phaeodactylum tricornutum (micro-algae) to accumulate elevated levels of the high value omega-3 DHA, increasing the amount produced 8 fold compared to the wild-type strain.

Click nucleic acid ligation

The synthesis of DNA constructs containing modified bases is becoming increasingly important due to very recent discovery of various DNA base analogues in the human genome and their central role in the epigenetic control of development, gene expression, disease and ageing. However, the assembly of genes with these modifications is beyond the scope of current methods of gene synthesis.

Tom Brown and collaborators at the Universities of Southampton and Oxford have developed a novel technology for the assembly of these constructs called click-chemistry. However, their modified DNA could not be copied accurately by DNA polymerases (these replicate DNA). To overcome these problems they used a slightly different DNA backbone, and this has so far enabled DNA constructs of over 300 bases to be made. Significantly this different backbone can be copied accurately by DNA polymerases.

Plants help clean up explosive-contaminated land

Pollution from explosives can pose a risk to both the environment and public health. A sustainable alternative to current decontamination methods is needed, as they are expensive and environmental damaging.

Research by Professor Neil Bruce at the University of York has enabled plants to remove explosive contamination, including TNT and RDX, from soil and water. This was achieved by transferring the pollution degrading abilities of certain bacteria into plants.

The research was originally funded by the BBSRC and the Ministry of Defence and has since attracted multi-million dollar backing from the US Department of Defense. Field trials at a US military site commenced in 2015.

Toolkit for a responsive biosensor

Scientists at Imperial College London, in collaboration with AstraZeneca, are currently working on generating a toolkit for biosensor networks to be used for small peptide signalling. If successful, the intention is that the toolkit could allow cells to respond to a physiological cue with the secretion of a therapeutic peptide. They are currently at the design stage and are creating a set of well-characterised standardised parts along with a streamlined assembly methodology.

As a proof of concept, they are working with a small handful of peptide hormones that could be used to design novel gene circuits for the treatment of obesity/diabetes.

Green Biologics Ltd

Green Biologics is a renewable chemicals company focussed on developing and delivering new renewable alternatives for everyday products.

A successful programme of strain and process optimisation utilising clostridial microbes to re-commercialise the acetone-butanol-ethanol (ABE) process has resulted in the recent acquisition of the company’s first commercial plant in Little Falls, Minnesota. This existing ethanol production facility is presently being retrofitted to utilise Green Biologics technology.

With unrivalled access to and understanding of an industrially proven clostridial culture collection and with the development of highly efficient proprietary genome modification technologies underpinning their strain improvement programme, GBL is now turning its focus to developing clostridia as a chassis strain for high value and specialist chemicals.

Synthetic biology approaches are being used in two ways. Firstly to generate microbes able to grow on a wide range of sustainable and renewable lignocellulose derived feedstocks for the next generation of sustainable, low cost production facilities. And secondly to build and optimise new chemical pathways for the new product opportunities identified.

Parasight – A rapid modular platform for parasite detection in developing countries

Researchers in Professor Paul Freemont’s laboratory at Imperial College London are currently developing biosensors for the detection of parasites.

The modular sensors work by detecting the action of specific proteases released by the parasites. As a proof of principle, they have successfully designed whole-cell-based biosensors that detect for Schistosoma mansoni, one of the causative agents of Schistosomiasis (bilharzia).

This is an important parasite to target in the first instance as estimates suggest 200 million people are infected by this group of parasites, with up to 700 million people at risk of infection in endemic regions. Indeed, further estimates indicate that the annual mortality rate for this disease is 280, 000 people in Sub-Saharan Africa alone. Future work will see the biosensor designs translated into an in vitro device to aid their application in the field via a collaboration with the Upstream Alliance whose aim is to reduce Schistosomiasis.

The Development of Bio-logical Devices

The development of bio-logic and bio-logical devices is an important area in the development of more advanced biological devices that are designed and built according to the application of systematic design principles.

Work by Professor Richard Kitney’s laboratory at Imperial College London in this area initially comprised the development of a range of logic gates. These are the direct biological equivalents of electronic logic gates that are the basis of all digital devices, such as smart phones and computers. The range of modular gates which were developed included stable AND, OR and NOT gates.

This work has now been successfully extended to the development of more complex biologically based digital devices, and, in particular, the development of a half adder. The half adder is an important step in the development of biological computational devices. The next step in the project is to develop a full adder.

The ability to undertake biological computation has a wide range of applications – for example, in relation to multichannel biosensors where decisions have to be made on the basis of multiple pieces of information. This also has important implications for the development of theranostic devices.

Sc 2.0 project

The Synthetic Yeast Genome Project is a global research effort aimed at completely synthesising and constructing a modern synthetic version of the S. Cerevisiae (baker’s yeast) genome. The synthetic yeast genome will be used to reprogram yeast and answer fundamental biology questions for example; how many genes can be deleted from a genome? It will also be a novel platform to synthesise commercially valuable products such as chemicals, antibiotics and vaccines.

The international consortium consists of researchers from the UK, USA, Singapore, Australia and China. The UK has contributed significantly to this project with BBSRC and EPSRC awarding £1 million to researchers working at Imperial to work on building and testing Synthetic Chromosome XI, which is 0.7 million DNA base pairs long.

Via the EraSynBio program, BBSRC has further awarded £0.7 million to researchers at the University of Edinburgh to build a new ‘tRNA neochromosome’ that is essential for the synthetic yeast genome. This is being tested in collaboration with both the Imperial team and with BGI (Beijing Genomics Institute) scientists currently based at Edinburgh who are nearing completion of Synthetic Chromosome 2.

Sentinel bacterial cells for homeostatic regulation of extra-cellular concentrations

A project led by scientists from Imperial College London (Dr Guy-Bart Stan and Dr Karen Polizzi), in collaboration with responsible research and innovation researchers at King’s College London (Dr Claire Marris) is currently engineering bacterial cells that can sense extra-cellular target molecules and, in response, take action to automatically maintain the concentration of these molecules around a desired set point.

The system is based on the in vivo implementation of an integral feedback mechanism with interchangeable sensing and production parts that can be easily modified to sense and automatically respond to different molecules. In collaboration with partners across various industries, they are exploring the use of this cell-based homeostatic regulation system for various applications, e.g. controllable cell-based therapies for the treatment of metabolic disorders, and bioreactor scale-up solutions where engineered sentinel cells could be used to monitor optimal growth conditions in bioreactors and automatically correct deviations from these.

In collaboration with researchers at King’s College London, the broader societal, economic and regulatory implications of this research are being explored, in particular in the context of its use for the development of controlled cell-based therapies. To this end, researchers at Imperial and King’s are conducting a set of key interviews and organising an international workshop gathering key stakeholders, i.e. academic world-leaders, industry and start-up CEOs, UK and US regulators, clinicians, patient groups, and social scientists. The key findings of these interviews and of the workshop will be used to further inform future regulations and anticipatory governance pertaining to synthetic biology research for cell-based therapies.

GSK

Innovate UK support is a key factor in GSK being prepared to pursue novel Synthetic Biology approaches over more traditional ‘tried and tested’ alternatives. Funding presented an opportunity to leverage UK science and lead development in an efficient and rational manner, with potential to feed directly into the existing GSK improvement programme. By stimulating research and development in this way, productivity gains can be achieved while also reducing the environmental impact of an established industrial facility, creating a more efficient UK production process.

Collaborating with UK academia has allowed engagement with world leading expertise and technology, while in return facilitated industrial support of UK science via exposure, education and training. Relationships such as this bring long-term benefits to both partners, protecting significant direct and indirect UK employment through the development of UK science and manufacturing, thereby ensuring a long-term lead in both.

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For more information about this article please contact our sector lead
Dana Heldt
Knowledge Transfer Manager – Synthetic Biology