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Scientific breakthroughs and applications

BBSRC-supported scientists are world leaders in many areas of bioscience.

Although the case studies on this page are primarily of scientific impact, many will also have economic, social and policy impact.

January 2010 - Communication skills: University of Kent students write letters to the Science Minister

Dear Minister,
Model organisms further understanding of disease

Many humans are known to be carriers of infectious fungi and bacteria. A healthy individual’s immune system is able to cope with the infections caused. However, within the immuno-compromised population, if infection occurs there are extremely high mortality rates. Fruit flies are used as a model organism for humans in terms of immunity against fungal and bacterial infection. Fruit flies and humans share a remarkably similar immune system that is activated in response to fungi and bacteria. It is important to understand the interactions between the patient and the infecting disease, as understanding of these interactions will enable the development of new prevention and treatment techniques.
Richard Roberts

Dear Minister,
Models of motor neuron disease in yeast

We are using yeast cells to model genetic alterations in the enzyme superoxide dismutase (SOD), which is associated with the disease amyotrophic lateral sclerosis, a form of motor neuron disease thought to affect around 3,500 people in the UK. Mutations in the SOD molecules cause them to stop working and clump together, effectively poisoning cells in the brain stem and spinal cord. Mimicking this in yeast allows us to look at where clumping occurs and how this might be affected by ageing. Ultimately we will explore how novel proteins as well as chaperones might be used therapeutically to break up clumps or prevent them forming.
Emma Bastow

Dear Minister,
When bugs go bad

Harmless bacteria and fungi living in the normal skin flora and mucous membranes of the human body are able to attack any tissue when it is weakened, and even cause death when the immune system is compromised. These microorganisms may become pathogenic in response to a change in carbon dioxide concentration, which is approximately 150 times higher in the blood than in the air. We are exploring the effects of carbon dioxide on growth, virulence and other characteristics of bacterial and fungal populations. By using various microbial mutants we hope to find a possible signal triggered directly by carbon dioxide and determine the position of this signal in the chain of microbial communication.
Miro Janco

Dear Minister,
Helping industry produce cheaper medicines

Some patients lose their life because they cannot afford vital but expensive medication. Treatment with Herceptin, for example, costs around £20,000 a year. Other patients may die due to lack of availability of the drug at the time it is needed. We are trying to optimise the strategy for making protein-based drugs in a cost- and time efficient way. Finding optimal conditions for efficient production of these proteins requires considerable optimisation, therefore any process that facilitates the development of efficient protocols would be highly beneficial to the bio-manufacturing industry and to the patients.
Farnaz Forouzandehfard

Dear Minister,
Engineering antibody molecules for enhanced stability

This project is funded by UCB and in collaboration with the University of Kent we are working towards making a more stable therapeutic antibody. Antibodies are prime candidates as therapeutics in areas such as auto immune diseases. However, there are problems associated with the molecule: certain antibody molecules tend to be unstable and can clump together. We are using the principles of protein engineering to alter some of the bridging bonds that hold the antibody molecule in shape to see if we can develop a more stable form which retains its activity and remains useful as a therapeutic, but is easier to manufacture.
Shirley Peters

Dear Minister,
Production of factor VIII for the treatment of haemophilia

Haemophilia is a rare blood clotting disorder resulting from either the lack of, or incorrect function of a protein found in the blood, factor VIII. Patients are treated by infusing factor VIII – so called ‘replacement therapy’. Currently the production of factor VIII is difficult and costly due to its large size and complexity. We are working to improve the production of factor VIII in animal cells with the aim of increasing the yield and lowering production costs. This will significantly improve the availability of treatment to haemophilia patients worldwide.
Caroline Tolley

Dear Minister,
Eukaryotic proteins undergo many post-translational modifications, some of which when not properly regulated can lead to conditions such as infertility, blindness and cancer. Bacteria such as Escherichia coli are used to produce proteins as it is relatively cheap and produces a good yield of protein. However when produced in E.coli eukaryotic proteins are rarely post-translationally modified correctly. This is because E.coli does not possess the appropriate machinery to carry out these changes. We are developing a novel system that permits the production of therapeutically relevant post-translationally modified eukaryotic proteins from E.coli.
Matt Johnson

Dear Minister,
With an increasing number of disease-causing microbes developing resistance to current antibiotics, the need for a new strategy to both detect and eliminate infectious agents is urgent. Radiation is known to kill cells, and this has been applied to medicine; for instance, it is currently used in a range of cancer therapies. This project aims to apply these therapeutic principles by selectively delivering toxic radiation to the infectious agent, using suitable molecular “delivery vehicles”. This could be a new way of combating infections by targeting specific microbes with radiation, without affecting the patient’s own tissues.
Claudia Rathje

Dear Minister,
Proteins fold to 3D-shape to allow their function. If proteins misfolding and subsequently aggregate and if this occurs in the brain it can cause severe neurodegenerative diseases such as Alzhimer’s disease. Chaperones are proteins required to maintain the shape of a protein to prevent inappropriate aggregation. How chaperones play a role in pathway of proteins folding. One useful model organism to explore the activities of chaperones is yeast Saccharomyces cerevisiae. Several different molecular chaperones have been identified in this yeast. Consequently, the function of chaperones will be investigatedin S. cerevisiae for a better understanding of their role in proteins folding.
Jintana Wongwigkarn

Dear Minister,
Bacterial Microcompartments
My research is in the area of synthetic biology, and the application of modifying bacterial cells to form valuable products, such as those with nutritional or therapeutic use. I am looking at bacterial cells and how they segregate into microcompartments to produce different chemicals and how the cells can be adapted to contain the selected compartments that make the desired products. If the bacterial cells can be tailored to manufacture high levels of these compounds, the cells can be used as mini-factories for their production.
Sarah Newnham

Dear Minister,
Understanding proteins that clump together
With funding from the Thai government, BBSRC and UCB in collaboration with the University of Kent we are able to study the effect of human disease using models. We are using baker’s yeast as a model organism to understand the function of chaperone proteins which are needed to ensure that proteins fold up properly as they are being made. This is important because when proteins are mis-folded they clump together and this clumping can occur in the brain causing serious neurodegenerative diseases such as Alzheimer’s disease.

Many chaperones found in humans have also been discovered in yeast, making it a good system in which to study how they work.

Yeast cells can also be used to model genetic alterations in the enzyme superoxide dismutase (SOD), which is associated with the disease amyotrophic lateral sclerosis, a form of motor neuron disease thought to affect around 3,500 people in the UK.

Mutations in the SOD molecules cause them to stop working and clump together, effectively poisoning cells in the brain stem and spinal cord. Mimicking this in yeast allows us to look at where clumping occurs and how this might be affected by ageing. Ultimately we will explore how novel proteins as well as chaperones might be used therapeutically to break up clumps or prevent them forming.

We are also looking into this clumping effect in proteins by working towards making a more stable therapeutic antibody. Antibodies are prime candidates as therapeutics in areas such as auto immune diseases. However, there are problems associated with the molecule: certain antibody molecules can be unstable and tend to clump together. We are using principles of protein engineering to alter some of the bridging bonds that hold the antibody molecule in shape to see if we can develop a more stable form which retains its activity and remains useful as a therapeutic, but is easier to manufacture.
Jintana Wongwigkarn, Emma Bastow, Shirley Peters

October 2009 - Honeybees to join creative counter-terrorism arsenal

Scientists have recruited some unlikely allies in the quest to enhance security. The honeybee, Apis mellifera, can be trained to react to the tell-tale odours of explosives. Quicker, cheaper, and easier to train than sniffer dogs, enlisting bees at airport security checkpoints could save lives and make travel safer across the world.

It’s all down to the bees’ incredibly sensitive sense of smell that can detect molecules at parts per trillion – orders of magnitude greater than human-made electronic detectors – which can be fine-tuned to react to the presence of explosives by feeding the bees sugar while they are exposed to the smell of the targeted explosive, such as TNT or even the synthetic plastic explosive C-4 which is notoriously difficult to detect.

Since 2003, Inscentinel Ltd., a technology spin-out company based at Rothamsted Research – an institute of the Biotechnology and Biological Sciences Research Council (BBSRC) – has busied itself honing the technology and prototype equipment. The company is supported by private investors such as Oxford Technology and also the Rainbow Seed Fund, which specialises in commercialising innovative research, and has recently completed Government trials by attracting the support of the UK Home Office.

The technology has already found its way to the US military when it was tested at Los Alamos under a project called the Stealthy Insect Sensor Project.

Finding mines and debugging bombs is worthy work, but it’s not all military. Bees can seek out dry rot, be trained to work toward improving food quality and safety, in drug detection, and one day may even be able to diagnose diseases such as cancer and diabetes from a person’s breath.

August 2009 - Spin-out looks to repair torn cartilage with stem cells

Azellon describes itself as a' virtual company'. But it has already attracted seed funding of over £1.5M. It is planning clinical trials next year of its technique for repairing torn meniscal cartilage in the knee with a 'bandage' containing new cartilage cells derived from patients' own stem cells.

The technology has been developed by Professor Anthony Hollander and colleagues at the University of Bristol and is another example of how the team is translating its science into clinical applications. In 2008, they were part of the team that successfully transplanted a piece of windpipe (trachea) coated with her own stem-cell derived cartilage cells into a patient in Spain.

The technique for making the cartilage cells was originally developed several years ago through BBSRC-funded research at the University. Professor Hollander is Chief Scientific Officer and co-founder of Azellon.

July 2009 - Award-winning test for herbicide-resistance

A rapid way of testing and quantifying the degree to which weeds have become resistant to herbicides is a crucial tool in enabling arable farmers to  manage resistance. The ‘Rothamsted Rapid Resistance Test’ was originally devised by Dr Stephen Moss (pictured) in 1999, and has been progressively refined and revised as new types of resistance have evolved and new herbicides have become available. The test is now deployed extensively as a ‘standard’ by organisations and companies across the UK, and abroad, and has underpinned new strategies for preventing, defining and managing herbicide-resistance.

Grass weeds such as blackgrass, ryegrass and wild oats cause serious problems for arable farmers in many countries. Resistant forms of the weeds have evolved extensively in fields where herbicides have been used regularly. For example, resistant blackgrass has been found on over 2000 farms across 32 English counties. 

The resistance test developed by Dr Moss and colleagues requires no sophisticated equipment, which is a primary reason why it has been widely used.  The practical interpretation of the results is greatly enhanced by the inclusion of standard reference populations which have been fully characterised, not only at the whole plant level, but also at the biochemical and molecular level.  

A resistance rating system describes the severity of resistance and this provides a standard framework for monitoring resistance and for ensuring that farmers receive the most appropriate advice.  This is particularly important as the threat from resistant weeds is likely to increase with more autumn sown crops, earlier planting, more reduced tillage and the withdrawal of some herbicides on environmental grounds.  The lack of any herbicides with new modes of action in the near future makes farmers increasingly dependent on a smaller armoury of existing herbicides, which increases the threat from resistance.        

Crucially, the Rothamsted test can alert farmers to resistance to new or ‘low resistance risk’ herbicides before problems become apparent in the field. This enables them to take early action to contain the problem by using more non-chemical weed control methods and reducing their reliance on herbicides. 

Dr Moss won the 2009 Technology Award of the Royal Agricultural Society of England (RASE) in recognition of the practical impact of his research which was considered fully in keeping with the RASE motto, ‘Practice with Science’.   

March 2009 - Innovator of the Year

This awards honours top UK bioscientists who have turned world-class research into a product, company, service or advice, which has an impact on our lives.

Prof Stephen Jackson from the University of Cambridge won the inaugural 2009 award, and a cheque for £10,000.

Prof Jackson established KuDOS Pharmaceuticals in 1997 after discovering the possibility of developing drugs that prevent certain DNA repair proteins from working in cancer cells, leaving normal cells unaffected. With an applied genomics LINK grant, KuDOS developed an inhibitor of the DNA repair enzyme PARP. The drug kills BRCA-defective cancer cells, and is less toxic to normal cells than most other drugs.

AstraZeneca purchased KuDOS in 2005 for £120M.

Earlier impacts

'Medicines' in animal milk

Scientists at the then Institute of Animal Physiology and Genetics Research (now Roslin Institute) were the first to demonstrate, in the late 1980s, that medically important human proteins could be produced in the milk of transgenic animals (i.e. animals into which copies of human genes have been introduced). Initial work using mice showed that yields could be increased by inserting non-coding introns into the DNA sequences used to produce the transgenic animals.

Antibiotics chemistry and genetics

Biochemists and chemists and the University of Cambridge and geneticists at the John Innes Centre have characterised biosynthesis and the nature of natural polyketide antibiotics. This has opened up new opportunities for the design of a range of novel therapeutics including novel antibiotics and anti-cancer drugs.

Biology of stem cells

Researchers at the University of Edinburgh pioneered the study of how stem cells regulate themselves either to replicate as unspecialised cells or differentiate into specialised types of cells. They have identified several key regulatory proteins involved in these pathways. For example, they showed for the first time that proteins that switch genes off are directly involved in committing embryonic stem cells to specialise. Institute for Stem Cell Research (ISCR) researchers were also among the first to grow specialised nerve cells from stem cells in the laboratory.

Body clocks

In the 1970s and 80s, scientists at several UK universities and research institutes located the biological clocks in mammals and birds, and showed the major centre to be a concentration of cells in the hypothalamus, a small region at the base of the brain. For example, scientists at the University of Bristol characterised the interplay of light, receptor cells and hormones in day-length driven effects in birds. More recently, researchers at Imperial College London found receptor cells in the mammalian eye that gather information about the time of day, a function previously imagined to be the job of the rod and cone cells of the retina. This has opened up new approaches to exploring the nature and healthcare implications of mammalian body clocks, for example in areas such as night time shift working and Seasonal Affective Disorder.

BSE, scrapie and CJD

Scientists at the former Neuropathogenesis Unit (now part of Roslin Institute) and other BBSRC-supported researchers played a major role in identifying the nature of the family of diseases that includes BSE. This built upon a longstanding research programme on the sheep disease scrapie. By the mid 1980s at least 20 strains of scrapie had been identified. Later in the decade, data on amino acid sequences and patterns of protein glycosylation revealed strong similarities between prion proteins in BSE and their counterparts in scrapie. In the mid 1990s glycoform signatures showed that proteins in variant CJD resemble BSE proteins more than proteins in other types of CJD.

Cell signalling

Professor Sir Michael Berridge established a world leading laboratory at the then Institute of Animal and Physiology Research (now Babraham Institute) that characterised  the 'second messenger system' by which chemical messages arriving at a cell are relayed from receptors on the outside of the cell, through the membrane and into the cell's interior. This signalling cascade proved to be ubiquitous in living systems and to regulate a wide range of processes including secretion, contraction, neural activity and cell proliferation.  This work was the basis of the second most cited paper in the world's scientific literature of the 1980s.

In the mid 1990s collaborative research between microbiologists at the Universities of Nottingham and Warwick revealed an unexpected chemical language (signalling) based on small molecules by which bacterial cells communicate with each other. Until this time, it had been imagined that individual cells were self-sufficient entities that operated independently. The finding revolutionised ideas about how to control disease-causing bacteria, how to screen and use bacteria as biological factories for antibiotics and other high-value compounds and how to detect species that cannot be cultured in the laboratory.

Cloning (nuclear transfer technology)

Research at Roslin Institute showed for the first time, with the production of the cloned sheep Dolly, that fully specialised mammalian cells from tissues in adult animals can be reprogrammed to form a new embryo from which a new animal can be produced. The technology involves inserting the nucleus, which contains the chromosomes, from a specialised cell into an unfertilised egg cell from which its own nucleus has been removed. This technology has led to a completely new area of biological research and opened up the possibility of therapeutic cloning to support novel cell- and tissue-based treatments.

Epigenetics

Researchers at Babraham Institute identified a mechanism that explains how, for some genes, the copy from one parent is silenced in the offspring while that from the other parent is active. This phenomenon is known as imprinting. It is important in several hereditary disorders.

The same group has shown that faulty imprinting in a gene that helps regulate cell growth results in a rare condition (Beckwith-Wiedemann syndrome) leading to babies with abnormally large birth weights and an increased risk of some childhood cancers.

Gene and genome mapping

Bioscientists in UK universities and research institutes have been leaders in gene mapping and genome analysis in plants, animals and microbes, often as part of large multinational research consortia. They have also contributed greatly to the understanding of synteny (i.e. the extensive similarity of genes and genetic organisation across species which makes it possible to use data from relatively simple organisms as guides to more complex species including humans). Examples include Arabidopsis, which is a model for brassicas and other crops and was the first plant genome to be sequenced (2000), and yeast. About 40% of the genes responsible for heritable diseases in humans have counterparts in yeast.

UK researchers are also international leaders in the sequencing and analysis of genomes of strategically important species including rice (genome sequenced 2005); chicken (genome sequenced 2004); and Streptomyces (genome sequenced in 2002), part of the family of microbes that provide over half of the worlds antibiotic medicines.

Glycoproteins

Researchers at Imperial College London are world leaders in structural analysis of sugar molecules that are attached to proteins and which are important in cell-to cell recognition and communication. The sugars, which are potential targets for novel vaccines and drugs, determine a range of functions including immune responses to invading pathogens and sperm-egg recognition.

Insect semiochemicals (behaviour-controlling chemicals)

Scientists at Rothamsted Research elucidated the chemistry of signalling processes that determine interactions between invertebrates, and between plants and invertebrates. This has led to new insights into the relationships between crops and pests, and between predator and prey species. This knowledge informs the design and implementation of biological control systems and other environmentally friendly practices in land management.

Liposomes

Research into the properties of phospholipids at the then Institute of Animal Physiology (now Babraham Institute) led in the 1960s to the discovery of liposomes. These small artificial vesicles became versatile tools for research in biology, biochemistry and medicine. They were also taken up in a variety of commercial applications, for example in the pharmaceutical and cosmetics sectors.

Plant molecular biology

Plant scientists in the UK have made a major contribution to advances in the understanding of genes that control flowering, plant development, and resistance to pests and diseases, as well as in the development of DNA-based technologies to accelerate the introduction of beneficial traits into crops. Examples include the pioneering of 'antisense' technology to study and manipulate plant gene function (University of Nottingham) and elucidation of the genetic regulation of flowering time, flower shape, pigmentation and location (John Innes Centre, University of Edinburgh).

Plant molecular biology at the John Innes Centre and the University of York has also revolutionised understanding of the role of plant hormones in plant growth, and provided a basis for the application of this knowledge in crop breeding. For example, in 1999 scientists at the John Innes Centre characterised in Arabidopsis a dominant dwarfing gene, and so provided an explanation of the processes behind the development of short-stemmed wheats in the 1960s and 1970s. The Arabidopsis gene might be used as a guide to identify similar genes in other crop species. This offers plant breeders a way to convert any locally-adapted, low-yield variety of crop into a higher yielding form, without disturbing the plant's adapted genetic background.

Structural basis of photosynthesis

Combined chemistry and structural biology at the University of Glasgow on the light harvesting complex from photosynthetic bacteria helped to reveal how the complex can absorb energy and feed it into the reaction centre.

The integration of protein structure science and biochemistry at Imperial College London provided a detailed picture of the photosynthetic reaction centre complex that is responsible for splitting water into hydrogen and oxygen - the reaction in which life on Earth ultimately depends.

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