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Kinases, the enzymes that catalyse phosphorylation events, have been implicated in hundreds of different diseases, and hold rich promise for drug development. In 1998, The University of Dundee developed the first systematic assay to analyse the selectivity of protein kinase inhibitors, termed `kinase profiling'. This technology has been crucial for the development of new therapeutic drugs targeting protein kinases. In order to promote drug discovery in the area of kinases, the Division of Signal Transduction Therapy (DSTT) was formed and provides a unique collaboration between the University and six of the world's leading pharmaceutical companies.
The Institute of Cancer Research (ICR) founded the spin out company Domainex in 2002 in collaboration with UCL and Birkbeck. The company was set up on the basis of novel research into the expression of soluble protein domains to provide services to a range of bioscience-based companies. Within the period 2008-2013, Domainex has established profitability and positioned itself as a successful company employing over 30 scientists at its laboratories in Cambridge. It has established programmes and contracts with over 20 international clients in medicinal chemistry, drug discovery, monoclonal antibody development and agrochemical science, making a major commercial impact in all these fields.
PKB (protein kinase B), also known as AKT, is an enzyme in the PI3 kinase/mTOR intracellular signalling pathway, which is deregulated in many cancers. Professor David Barford's team at the ICR solved the crystal structure of PKB03b2 using innovative protein engineering. The ICR has licensed six international pharmaceutical companies with reagents to enable them to begin PKB drug discovery programmes. The Barford team has also used their structural biology expertise to advance the ICR's own PKB inhibitor drug discovery programme. Two series of inhibitors were developed that were licensed to AstraZeneca and Astex and are now both in clinical trials.
In 2003, researchers at the University of Dundee identified the tumour suppressor LKB1 as a critical upstream activator of AMP-activated protein kinase (AMPK), which provided the first link between AMPK and cancer. Metformin, the front-line therapy for type-2 diabetes, was already known to exert its beneficial effects through AMPK. An interdisciplinary collaboration at the University examined the link between metformin and cancer, and reported in 2005 that diabetics taking metformin had a reduced incidence of cancer. The impact has been clinical trials worldwide testing the benefit of metformin for cancer treatment, and development of therapeutics by pharmaceutical companies targeting this pathway.
Combinatorial Domain Hunting (CDH) technology is a technique for producing fragments of proteins that are soluble and tractable for biophysical analysis. It was developed between 1999 and 2008 at Birkbeck College, in the laboratory of Dr Renos Savva. This technology was patented in 2001 and the biotech company Domainex Ltd was then formed to commercialise it. In 2007, Domainex merged with a UCL spinout company, NCE Discovery Ltd. The company has attracted over £3m in investment and employs about 31 people. In addition to its contract research programme, it has developed an in-house drug discovery programme utilising CDH. Early in 2012 a patent was filed on a series of inhibitors of the protein kinases IKK03b5 and TBK1, which are validated drug targets for cancer and inflammation, and the first of these are expected to begin clinical trials in 2014.
Protein kinase B (PKB), also known as AKT, is an enzyme in the PI3 kinase/mTOR intracellular signalling pathway, which is found to be deregulated in many forms of cancer. Professor David Barford's team at the ICR solved the crystal structure of PKB03b2 using innovative protein engineering and licensed six international pharmaceutical companies with reagents to enable them to begin PKB drug discovery programmes. The ICR also initiated its own PKB drug discovery programme: two series of inhibitors were developed that were licensed to AstraZeneca and Astex and are now both in clinical trial. The ICR's work helped to establish PKB as a valid cancer therapeutic target. The ICR is involved in clinical research studies of multiple PI3 kinase and PKB inhibitors, and this research has led to the definition of useful clinical pharmacodynamic biomarkers.
Members of the Pharmacology Research Group identified hitherto unknown properties of G protein Coupled Receptors (GPCRs): that ligands can signal differentially through both G-protein-coupled and β-arrestin pathways. This led to the concept of GPCR `biased signalling' and development of fluorescent reporters to quantify β-arrestin signalling. These discoveries have been adopted widely by the pharmaceutical industry, attracting R&D investment and collaborative research funding, to drive discovery of new drugs operating through `biased signalling'. The commercial opportunity has also been exploited by screening reagent providers and contract screening organisations. These discoveries will ultimately produce better drugs to treat GPCR-based diseases to improve human health.
Professors Zhelev (UoA5) and Bradley (UoA15) explored the scope and demonstrated the feasibility of using light-scattering methods for quantitative analysis of macromolecular associations and aggregation, including protein-protein and protein-DNA interactions. 16 years of design and development research was translated into a marketed product — the PAM™Zero — a novel hand-held, low-cost protein aggregation monitor capable of detecting macromolecule aggregation in microliter sample volumes. Manufactured and sold through a spinout company, Norton Scientific Inc. (established in 2010 and valued at $7M), this portable instrument is used in commercial Quality Control and academic research and has been sold to a range of stakeholders e.g. drug development companies, for food safety and water pollution monitoring.
The Fuller Longer™ (FL) food range was developed by Marks & Spencer (M&S) with expertise from the University of Aberdeen Rowett Institute of Nutrition and Health. Product development was based on Rowett research into the efficacy of high protein and mixed carbohydrate diets for sustained appetite control and weight loss. Obesity is a major public health challenge; therefore it is not surprising that FL has become an established brand for M&S's 20 million customers. This industry-academia partnership to develop a food range based on scientific input, was a first for M&S, and has led to one of the UK's most popular retail healthy-eating food ranges.
Therefore the claimed impact here includes benefits to health and welfare, on commerce, business performance and the economy.
Research in protein folding and technological development at the University of Leeds led to the creation of Optim1000, a high throughput microlitre protein stability analyser, through Leeds spin-off company Avacta. Used in the early stages of R&D in the biopharma industry, Optim1000 evaluates the stability and homogeneity of complex biological drugs, using just micrograms of protein sample. This screening reduces the costly development and late-stage failure of unsuitable candidate therapeutics. The platform has been sold to a wide range of global biopharma companies; it is reported to reduce drug stability screening by months. This provides economic impact through saving the industry millions of dollars in R&D costs, along with health impact by speeding up the emergence of new products. Avacta reported revenue of over £3 million in 2012 and employs 70 staff.