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The Basidio Molecular Toolkit developed at the University of Bristol has enabled the pharmaceutical industry to achieve the efficient genetic manipulation of a group of basidiomycete fungi (mushrooms and toadstools) and thereby produce medically important antibiotics and proteins cost-effectively. For example, GlaxoSmithKline's collaboration with the Bristol team saved 70,000 hours of research and development in getting a natural antibiotic called pleuromutilin to market. In China, the system is used to produce medicinal anti-cancer proteins from fungi in commercially viable quantities. In addition, government agricultural research programmes in the US and Ireland have adopted the toolkit to increase the efficiency of their search for disease-resistant crops in the interests of farmers, consumers and economies.
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.
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.
Haemophilia, an inherited bleeding disease, is treated by frequent and extremely expensive infusions of recombinant versions of the missing factors. Advances in gene therapy have now been achieved at UCL, with successful treatment of Haemophilia B in 10 severely affected patients. The novel factor IX expression cassette has been patented and licensed to an industrial partner (UniQure). Savings to the NHS in excess of £1.5m have already been made and increase every month. Pre-clinical advances have also been made in Haemophilia A, and the factor VIII expression cassette has been patented and licensed to an industrial partner (BioMarin).
Targeted Projection Pursuit (TPP) — developed at Northumbria University — is a novel method for interactive exploration of high-dimension data sets without loss of information. The TPP method performs better than current dimension-reduction methods since it finds projections that best approximate a target view enhanced by certain prior knowledge about the data. "Valley Care" provides a Telecare service to over 5,000 customers as part of Northumbria Healthcare NHS Foundation Trust, and delivers a core service for vulnerable and elderly people (receiving an estimated 129,000 calls per annum) that allows them to live independently and remain in their homes longer. The service informs a wider UK ageing community as part of the NHS Foundation Trust.
Applying our research enabled the managers of Valley Care to establish the volume, type and frequency of calls, identify users at high risk, and to inform the manufacturers of the equipment how to update the database software. This enabled Valley Care managers and staff to analyse the information quickly in order to plan efficiently the work of call operators and social care workers. Our study also provided knowledge about usage patterns of the technology and valuably identified clients at high risk of falls. This is the first time that mathematical and statistical analysis of data sets of this type has been done in the UK and Europe.
As a result of applying the TPP method to its Call Centre multivariate data, Valley Care has been able to transform the quality and efficiency of its service, while operating within the same budget.
This case study describes the impact of discoveries by Griffin and Handyside on the universal detection of genetic disease in IVF embryos. The team used basic research to develop practicable new techniques now employed in IVF clinics around the world and culminating in a process named "Karyomapping". The impacts are far-reaching and significant: when applied to families at risk of transmitting genetic disorders the process has resulted in live births of unaffected children. The positive results of the discoveries have extended beyond clinical applications: Adaptations of the technology are now being translated to farm animal breeding regimes to improve meat yields and reduce environmental concerns. Impact also includes new product development and wealth generation, job creation, education, and influence on public policy through HFEA, plus widespread public engagement and communication.
BEAA research has impacted positively on commerce in brewing and biotechnology companies worldwide through continuous collaboration with Aber Instruments, an AU spin-out company formed to commercialise university research. Aber Instruments has supplied over 1000 fermentation monitoring systems world-wide for the on-line measurement of viable biomass concentration, providing improvements in speed and accuracy over previous off-line, culture or stain-based procedures. On-line, real-time monitoring of viability during fermentation reduces costs and improves product quality, leading to practitioners in large breweries including Anheuser Busch, SABMiller, Inbev, Coors, Diageo, Heineken, Suntory and San Miguel adopting the Yeast Monitor as part of their standard operating procedures. The new Futura instrument, which utilises the same technology developed from BEAA research, was launched in 2009 and is now used by major biotechnology companies including Genetech, Novo, Biogen Idec, GlaxoSmithKline, Centocor, Sandoz, Eli Lilly and Genzyme to monitor biomass in a much wider range of fermentations.
In genetic studies of human disease it is now routine for studies to collect genetic data on thousands of individuals with and without a particular disease. However, the genetic data collected is incomplete, with many millions of sites of the genome unmeasured. The novel methods and software (IMPUTE) developed by researchers at the University of Oxford predict unobserved genetic data using reference datasets.
IMPUTE has been adopted by the company Affymetrix in the design of custom genotyping chips. Affymetrix recently won the tenders by the UK Biobank and UKBiLEVE studies to genotype >500,000 participants, with a total study cost of ~£25M. The company states that IMPUTE gave their project bid a significant competitive advantage. Affymetrix also purchased the IMPUTE source code for £250,000. In addition, Roche Pharmaceuticals have used the software in their research on the genetic basis of drug response. The use of imputation has saved Roche ~$1,000,000.
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.
The International HapMap project was a major international research collaboration to map the structure of common human genetic variation across populations from Europe, Asia and Africa. Mathematical Scientists from the University of Oxford played key roles in the development of statistical methods for the project, along with its overall design and management of the International HapMap Project.
Companies have used HapMap as the primary resource to design genome-wide microarrays to make novel discoveries in, for example, pharmacogenetic studies. The size of this market is estimated at $1.25 billion.
One novel discovery has led to a genetic test that is predictive of sustained viral suppression in patients treated for chronic hepatitis C. An estimated 2.7 to 3.9 million people are affected by HCV infection. This test is sold commercially by the company LabCorp and is a significant contributor to the company's testing volume. Finally, the project has been important in widening the public understanding of genetic variation.