Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.1.1-2 | Award Amount: 16.07M | Year: 2011
Embryonic stem (ES) cells have the potential to differentiate into any type of cell as well as to renew indefinitely in culture. They hold great potential for the development of personalized medicines. However, the molecular mechanisms underpinning cell fate decisions by individual cells are poorly understood. There is compelling evidence that two large multi-protein machines, the Nucleosome Remodelling and Deacetylation (NuRD) complex and the Polycomb Repressive Complexes (PRCs), modulate chromatin structure to control stem cell renewal, lineage commitment and differentiation. Moreover, they are clearly implicated in cancer. The goal of 4DCellFate is to understand how the PRC/NuRD complexes and their plethora of interactions (protein/protein, protein/nucleosome, protein/nucleic acids) regulate cell fate. To obtain this global, quantitative and dynamic 4D understanding of the structure/functions of these two multi-protein machines during ES cell differentiation and in different disease states, we propose a large scale multi-disciplinary data-gathering approach combining European excellence in interactomics (affinity purification, quantitative mass spectrometry-based proteomics, ChIP-seq analysis, light microscopy), structural biology (X-ray crystallography, NMR, native-state mass spectrometry, Electron Microscopy, biochemistry/biophysics), cellular, tumour, and computational biology. We expect to significantly advance the technology, mainly in the fields of proteomics, structural biology, and small molecule screening, and to make our knowledge, reagents and data publicly available to the scientific community. The ultimate outcome of 4DCellFate will be to lay the foundations for understanding the role of the PRC/NuRD complexes in ES cell differentiation and cancer, specifically in leukaemogenesis. Three SMEs and one large multi-national pharma will be actively involved ensuring that our findings can be translated into new ways to control complex diseases.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.2-1 | Award Amount: 7.88M | Year: 2013
Atherosclerosis and its most disabling sequelae, coronary artery disease (CAD) and stroke, are leading causes of death in Europe. Until now, preventive and therapeutic interventions for these diseases aim at ameliorating the effects of established cardiovascular risk factors. More recently, results of genome-wide association (GWA) studies added to our perception of mechanisms leading to atherosclerosis. At present, over 40 CAD and several genomic risk loci have been identified, the majority through efforts led by the applicants. Some genes at these loci work through known risk factors such as lipids and, in fact, are already established or evolving treatment targets. However, this is not true for the majority of risk variants, which implies that key pathways leading to atherosclerosis are yet to be exploited for therapeutic intervention. This EU network (CVgenes@target), which brings together an equal number of SME- and academic partners, will utilize genomic variants affecting atherosclerosis risk for identification of both underlying genes and affected pathways in order to identify, characterize, and validate novel therapeutically relevant targets for prevention and treatment of CAD and stroke. In programme 1 we will investigate molecular mechanisms at the genomic loci in order to further unravel causal genes, in programme 2 we will explore in vitro and in vivo whether the pathways disturbed by causal genes are suitable for therapeutic intervention, and in programme 3 we will establish assays and initiate high throughput screens to tackle therapeutically attractive targets. Our resources including large OMICs and state-of-the-art bioinformatics platforms as well as multiple, already established in vitro and in vivo models support the feasibility of the approach. In fact, two genomic risk loci (ADAMTS7 (CAD); HDAC9 (stroke and CAD)), both identified in GWA studies under direction of the applicants, already revealed attractive targets for therapeutic intervention.
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.3.2-01 | Award Amount: 9.93M | Year: 2012
SeaBioTech is a 48-month project designed and driven by SMEs to create innovative marine biodiscovery pipelines as a means to convert the potential of marine biotechnology into novel industrial products for the pharmaceutical (human and aquaculture), cosmetic, functional food and industrial chemistry sectors. SeaBioTech will reduce barriers to successful industrial exploitation of marine biodiversity for companies more accustomed to terrestrial biotechnology. SeaBioTech directly addresses five key challenges to remove bottlenecks in the marine biodiscovery pipeline, leading to (1) improvements in the quality of marine resources available for biotechnological exploitation, (2) improvement in technical aspects of the biodiscovery pipeline to shorten time to market, and (3) developing sustainable modes of supply of raw materials for industry. The two last challenges centre on enabling activities to enhance the marine biodiscovery process: first, clarification of legal aspects to facilitate access to marine resources, their sustainable use, and their secure exploitation; second, to create an improved framework for access to marine biotechnology data and research materials. To achieve its goals, SeaBioTech brings together complementary and world-leading experts, integrating biology, genomics, natural product chemistry, bioactivity testing, industrial bioprocessing, legal aspects, market analysis and knowledge exchange. The expertise assembled within the consortium reflects the industry-defined needs, from the SME partners initial definition of market and product opportunities to their ultimate proof-of-concept demonstration activities. SeaBioTech will have significant impact on research and technology, on innovation, on European competitiveness and on economic growth. It will provide a model to accelerate the development of European biotechnology into a world leading position.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.1-8 | Award Amount: 8.20M | Year: 2011
Effective and long term treatment of cancer is now in sight, but will ultimately require an increasingly personalised approach where the right combination of drugs will be administered to the right patients, based on a detailed understanding of their genetic background and their co-associated sensitivity or resistance biomarkers. Efforts are specifically required to identify validated risk and patient-response stratification criteria, which can then be used to rationally develop companion diagnostic assays and more stream-lined clinical trials. COLTHERES will address these key issues by: 1) Molecularly profiling colon cancer patient samples using multiple omics based technologies for co-segregating lesions that could impart resistance to existing and emerging targeted therapies 2) The building and screening of predictive in vitro models based on this data, to enable the rapid and empirical determination of drug resistance biomarkers 3) The use of these models and of the clinical studies to prospectively screen for genes mediating resistance and sensitivity to targeted therapies in CRCs 4) The building of new algorithms to significantly accelerate the design of rational therapies, by integrating more predictive models, assays and biomarkers into all phases of drug discovery; including novel phase-0 (xenopatients) studies 5) The design of innovative and focused biomarker driven phase II trials based on knowledge gathered within the project COLTHERES has assembled a unique consortium, from both academia and industrial SMEs, of world- experts in the areas of; clinical design of innovative biomarker trials and improved therapeutic strategies omics technologies including genomic, transcriptomic, epigenomic and proteomic profiling Functional genomic and disease model-generation Bio-informatics and data analysis, to handle and interrogate the complexity of the data generated through the various approaches
News Article | February 22, 2017
— Mice models are indispensable in research activities dealing with human disease processes due to striking similarities between the anatomy, physiology, and genetics of humans and mice. These advantages promote scientific discovery, understanding of the functions of individual genes, mechanisms of different diseases, and the effectiveness and toxicities of various drug molecules. Mice models are the most popularly used animal models due to their small size, short generation time, accelerated lifespan, low cost, and requirement of less space. These factors help in accelerating the research and development of drug therapies. Complete report on mice model market spread across 269 pages, profiling 11 companies and supported with 116 tables and 46 figures is now available at http://www.rnrmarketresearch.com/mice-model-market-by-type-inbred-knockout-conditioned-technology-microinjection-embryonic-stem-cell-disease-oncology-immunology-cns-service-breeding-cryopreservation-quarantine-c-market-report.html . The market players are continuously focusing on innovations in mice models for research on various human diseases. The major factor driving the growth of the market is the growing innovations and advances in mice models providing increased options to researchers to conduct research activities in particular diseases. Even the popularity of technologies like CRISPR, used in creating gene knockouts, is expected to be a major growth opportunity for the market. On the other hand, factors like advancements in genetic techniques for the development of genetically modified rats have led to the increased usage of rat models, thereby restraining the mice model market to some extent. In addition, increased benefits from cryopreservation, and regulations & laws for the ethical use of animals are some factors expected to restrain the growth of the market. Moreover, the continuous need for improved mice models, advancements in zebra fish model development, and alternative methods to animal testing is some of the major challenges for the market. In 2016, the inbred mice are estimated to account for the largest share of the market, by type while genetically engineered mice models are expected to be the fastest-growing market segment, owing to high investments in the development of new and innovative knockout models that also increases the application areas for the models. Charles River Laboratories International, Inc. (U.S.), The Jackson Laboratory (U.S.), Taconic Biosciences, Inc. (U.S.), Envigo (U.K.), Laboratory Corporation of America Holdings (U.S.), JANVIER LABS (France), Harbour BioMed (China), TRANS GENIC, Inc. (Japan), genOway (France), and Horizon Discovery Group plc (U.S.) are some of the key players in the market. Order a copy of Mice Model Market by Type (Inbred, Knockout, Hybrid), Technology (CRISPR, Microinjection), Application (Oncology, Diabetes), Service (Breeding, Quarantine, Genetic testing) & Care Products (Bedding, Feed) - Analysis & Global Forecast to 2021 research report at http://www.rnrmarketresearch.com/contacts/purchase?rname=140183 . In 2016, North America is expected to account for the largest share of the market, followed by Europe, Asia-Pacific, and the Rest of the World (RoW).North America’s large share is attributed to the rising demands for monoclonal antibody production, continued and responsible use of animals ensured by animal care organizations, rising preclinical activities by CROs and pharmaceutical companies, growing stem cell research in Canada, and government support for the development of protein drugs in Canada. RnRMarketResearch.com is your single source for all market research needs. Our database includes 500,000+ market research reports from over 100+ leading global publishers & in-depth market research studies of over 5000 micro markets. For more information, please visit http://www.rnrmarketresearch.com
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.1-8 | Award Amount: 7.96M | Year: 2011
The strategic development of accurate biomarkers to predict response to therapy in cancer medicine will enhance clinical outcome and reduce the health economic impact of drug resistant disease. The PREDICT consortium will identify and validate predictive biomarkers for two drugs which have direct anti-tumour cell and anti-angiogenic activity and for which no established predictive biomarkers of tumour response exist: sunitinib, a multi-targeted tyrosine kinase inhibitor, and everolimus, an mTOR pathway inhibitor. Renal cell carcinoma (RCC), a disease sensitive to these agents, will serve as the model tumour type to identify predictive response biomarkers suitable for widespread application across diverse tumour types. PREDICTs biomarker discovery approach is based on the integration of genomics data from pre-operative RCC therapeutic clinical trials with novel personalised functional genomic screen datasets. We will systematically collect tumour tissue from monotherapy pre-operative window RCC clinical trials of 240 patients treated with everolimus or sunitinib and determine expression profiles, copy number aberrations, and genome-wide exon sequences of tumours before and after drug treatment. We will perform two types of RNA interference drug- and hypoxia-resistance screens: one using reverse transfection of commercial siRNA libraries into previously established RCC cell lines, and one using a novel approach through personalised tumour cDNA derived-shRNA library transduction of ex-vivo cultured autologous tumour cell lines. Bioinformatics integration of these complementary individualised clinical and experimental datasets will enable the rapid and cost efficient identification of predictive biomarkers and simultaneously define molecular mechanisms contributing to intrinsic and acquired drug resistant disease in vivo, yielding additional targets for therapeutic intervention.
Moore J.D.,Vernalis |
Moore J.D.,Horizon Discovery
Nature Reviews Cancer | Year: 2013
Cyclin-dependent kinases (CDKs) are regulated by both cyclin abundance and cyclin localization. Increased cyclin expression in cancer was first observed two decades ago, and its role in pathogenesis has been investigated in great depth. This Opinion article focuses on the spatial deregulation of cyclin expression and its potential link to oncogenesis. It describes the contexts in which particular cyclins have been reported to be mislocalized in neoplasia, reviews the mechanisms underlying the dynamic subcellular localization of CDK-cyclin complexes in normal cells, and discusses how these controls can be disrupted in cancer. It also outlines the mechanisms by which cyclin mislocalization might disrupt cell cycle control and interfere with faithful chromosome segregation. Finally, it discusses the extent to which cyclin mislocalization might facilitate tumorigenesis in human cancer.© 2013 Macmillan Publishers Limited. All rights reserved.
Moore J.D.,Horizon Discovery
Drug Discovery Today | Year: 2015
The addition of an RNA-guided nuclease, Cas9, to the gene editing toolbox has increased the accessibility of gene editing technologies by greatly simplifying the design of editing reagents. Only a single 75-100 nucleotide RNA is required to guide Cas9 to the target gene of interest, which has meant that the established infrastructure of short-hairpin RNA interference screen could be readily adapted to genome-wide knock out screens. Cas9-based editing technology should streamline the generation of animal and cell-line models, make the generation of activity-dead mutations in target validation routine, and enable the discovery of a new generation of targets across therapeutic areas. © 2015 Published by Elsevier Ltd.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 349.88K | Year: 2014
This project will deliver innovative products that drive the development of enhanced analytical systems to meet the changing needs of diagnosis and stratification of cancer patients. This will allow patients to benefit from recent advances in molecular pathology by delivering more reliable and earlier diagnosis, personalized therapies and disease monitoring to achieve improved outcomes. The project will develop, test and validate materials derived from cell lines that will be engineered to reflect the genetic modifications seen in different cancers. This approach will enable the project partners to produce new and highly innovative reference standards (including formalin fixed paraffin embedded cell blocks and genomic DNA) as well as methods and protocols that can be used in all laboratories to increase efficiency and sensitivity of diagnostic testing and enable standardized, controllable proficiency testing across all geographical locations.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Collaborative Research & Development | Award Amount: 1.23M | Year: 2015
This project will deliver a pipeline of engineered Chinese Hamster Ovary (CHO) cells with characteristics and performance that will enable improved manufacture of novel biologic products. Recent research has identified critical metabolic check points that control CHO cell growth, and characterised pathways controlling product integrity and yield. In this project we will use this knowledge to deliver multiple and combinatorial gene ‘edits’ in CHO cells to produce cells that deliver efficiency and cost gains in manufacturing processes for biotherapeutic products, and broaden the product range that can be manufactured in this system. The improved performance of the cells will be assessed in fermentors and scaled-up to “manufacture ready” processes to ensure that project outputs are translatable into the manufacturing setting and outcomes are widely disseminated to the UK academic and commercial bioprocessing communities.