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Bacteria of the Clostridium genus are of pathogenic, medical and industrial importance. Development by University of Nottingham School of Life Science researchers of three patented methods for genetic manipulation of clostridial species has led to licensing agreements for commercial exploitation of the methodology to enhance strains for chemical commodity and biofuel production and for targeted cancer therapy. These methods are providing significant world-wide impact by facilitating commercial R&D investment and technology developments in fields ranging from healthcare, through chemicals manufacture, to the environment.
Dr Brettschneider and collaborators proposed a conceptual framework for high-dimensional gene expression data quality assessment (QA) and developed a QA statistical toolbox tailored to short oligonucleotide microarray technology. The work has deepened understanding of sources of variation and has helped in removing noise and bias in microarray data sets. This has accelerated the invention of clinical instruments for molecular cancer diagnosis/prognosis. The toolbox has been applied widely, leading to impact through:
(A) process improvement in microarray facilities saving running costs, and standardisation of data quality targets ensuring reproducible research;
(B) individualisation of treatment decisions supported by enhanced data quality, thereby reducing healthcare costs through avoidance of unnecessary surgery and improved patient welfare.
The wheat-breeding industry, including some of the largest plant breeders and seed-development companies in the world, has benefited from decreased production costs and increased productivity as a result of research led by the University of Bristol and carried out between 2009 and 2011. The Bristol researchers developed the tools necessary to differentiate point mutations in the complex DNA structure of wheat. This was a critical step in wheat genotyping and led to the public release of 95% of the wheat genome in 2010 and the development, by Bristol, of a cheap, easy-to-use assay for industry. These advances were quickly embraced by industrial wheat breeders aiming to deliver new varieties of wheat with improved yields and desirable traits such as disease resistance. Limagrain, the world's fifth-largest producer of field seeds (including wheat) with €595 million in sales of seeds, realised a ten-fold reduction in costs and a ten-fold increase in throughputs in their breeding laboratory. With the wheat-seed business worth over £16 million annually in the UK and over £1.8 billion globally, the new genotyping tools generated by Bristol have had, and continue to have, a major impact on the wheat industry and its ability to respond to the challenges of climate change and population growth.
Impact on society (non-profit organisations) and public attitudes: The discovery of the reversibility of Rett syndrome in a mouse model for the disease has changed attitudes and awareness amongst families of sufferers and has led directly to the formation of two new charities: the Rett Syndrome Research Trust (US) and ReverseRett (UK).
Impact on health and welfare: Two new clinical interventions are being trialled with Rett syndrome patients.
Beneficiaries: Families living with Rett syndrome worldwide.
Significance and Reach: The research has given hope to thousands of families world-wide and has prompted an active philanthropic drive to fund research into a cure based on the UoE findings. The RSRT has raised $15 million since 2008. The incidence of Rett syndrome is 1 in 10,000 females. Some 16,000 individuals have Rett syndrome in the USA, and an estimated 2,400 in the UK.
Attribution: The research was carried out at UoE led by Adrian Bird. The critical underpinning paper was the UoE demonstration of reversibility (2007).
Genetically engineered plants are increasingly used to over-express foreign genes, including those for pharmaceutically valuable polypeptides. However, expression of transgenes is repressed via RNAi, a system that probably evolved to combat viral pathogens. In response, viruses themselves encode a "silencing suppressor protein" that counteracts this defence response. This was discovered by David Baulcombe and colleagues at the Sainsbury Laboratory at UEA, who exploited this phenomenon by introducing the suppressor gene into plants and improving them as hosts for transgene expression. RNAi Suppression Technology was patented worldwide and licensed for fees >£500k to several companies, including Medicago, that use it to generate plants that effectively produce pharmaceuticals.
Professor Dickson's research group at Royal Holloway has pioneered the enabling technologies for the development of genetic therapies for the incurable disease Duchenne Muscular Dystrophy (DMD). Dickson's group has, (i) cloned replacement copies of the normal DMD gene, (ii) identified a natural substitute for the defective gene, and (iii) demonstrated that synthetic DNA can be used to correct the defective gene. The work has created impact on health and welfare through the development and clinical trials of a series of investigational medicinal products for this hitherto incurable disease, several clinical trials, and impact on commerce through industrial investment and licensed patents.
Our research has established that Trimethylaminuria (TMAU) — a rare and distressing disorder where affected individuals excrete large amounts of odorous trimethylamine (TMA) in their breath, sweat and urine — is a genetic disorder, and is not, as previously thought, due to poor hygiene. This has transformed understanding in the medical community and the wider public of why some people have an extremely unpleasant `fishy' body odour, and has been crucial to helping individuals with TMAU who often suffer social isolation, rejection, depression and higher than normal suicide rates. The findings have led to genetic diagnosis and genetic counselling for TMAU in the UK, Europe, USA and Canada and the publication of guidelines for the diagnosis and treatment of the disorder.
Research by Professor Elizabeth Shephard at the UCL Research Department of Structural and Molecular Biology has led to identification of the genetic origin of Trimethylaminuria (TMAU), commonly known as fish-odour syndrome. This has led to genetic diagnosis and genetic counselling for TMAU in the UK, Europe, USA and Canada, and the publication of guidelines for treatment and diagnosis. Shephard has engaged closely with patient groups over the years to publicise her findings. There is now an increased understanding among medical practitioners and the public that the body odour produced is due to a metabolic defect of genetic origin, and is not due to poor hygiene.
Impact on commerce: A patented technique for separating methylated and non-methylated DNA has been licensed and a kit brought to market, along with other commercial reagent licenses.
Impact on health and welfare: The demonstration that two mechanisms of epigenetic gene regulation, DNA methylation and histone acetylation, are linked, has led to trials of separate drugs known to affect each mechanism as a combined treatment for high-risk patients with myelodysplastic syndromes (MDS).
Beneficiaries: Companies have gained commercial benefit from licensing UoE IP to market products. High-risk MDS patients will benefit from improved treatment.
Significance and Reach: Commercial earnings across 4 companies from international sales in the period estimated at over [text removed for publication], mainly since 2010. Commercial significance includes the first commercially-available technique for separating methylated and non-methylated DNA.
The incidence of MDS is estimated at 3-4 cases diagnosed annually per 100,000 of the population in Europe (an estimated 26,000 individuals) and up to 20,000 new diagnoses per year in the USA. Incidence increases with age — up to 15 new cases annually per 100,000 in individuals aged over 70 years. MDS occurrence is increasing as the age of the population increases, so the significance of new therapies is high.
Attribution: All research was led by Adrian Bird at UoE. Reik (Babraham Institute) contributed to development of one of the licensed antibodies.
Research carried out by the University of Southampton into the genetic causes of diseases, and the gene mapping techniques and applications derived from this research, has benefited patients worldwide through improved prediction, diagnosis and treatment for common diseases with a complex genetic basis. A particularly striking example is age-related macular degeneration which is a common cause of blindness. Commercially, the research provides cost-effective strategies for genotyping DNA samples, and marker-based selection strategies for economically relevant animal species, such as cattle. The work underpins the development of the personal genomics industry, which specialises in individual genetic risk profiling.