We are pleased to announce the development of a new machine learning approach to data analysis that is robust, more sensitivity and increases our understanding of gene-phenotype relationships. The method, recently published in PLoS One (http://dx.plos.org/10.1371/journal.pone.0052410), is adaptive to the complex data collected in high-throughput phenotyping pipelines. Applying this analysis method further optimizes the phenotyping work flow by using knockout mice in small independent batches and comparing this to a baseline control dataset. These changes have significant economical and ethical benefits as it reduces the use of animals, increases throughput, and decreases cost while improving the quality and depth of knowledge gained. Further work will refine the method to encompass all data types from the phenotyping process, validate the output and develop interpretation tools for biologists. These tools combined with IMPC data will create an unparalleled resource for gene function that will fuel future discoveries in mammalian and biomedical sciences.
News
The International Mouse Phenotyping Consortium (IMPC) announces that Taconic (www.taconic.com), a leading provider of life sciences solutions, has agreed to help support the mission of the IMPC by becoming a Corporate Sponsor. Taconic is a provider of mouse models and advanced scientific services and shares the scientific vision of the IMPC to determine the function of every gene in the mouse genome. The IMPC recently released a call for industrial partnerships for industry to work with the IMPC at a variety of levels. As a result Taconic has become the first corporate sponsor of IMPC. The call for partners is still open and IMPC welcomes further industrial partners and sponsors to support the efforts of IMPC.
Taconic desires to support the IMPC’s worldwide efforts, namely producing knockout mice, conducting phenotyping of each line, and making those lines readily available to the research community for use in basic scientific research and the generation of new models for human disease. Taconic can support the IMPC in two essential ways: by offering mouse models with stable and genetically consistent backgrounds, and by offering advanced breeding technologies to IMPC members and the research community in order to have fast and easy access to study-ready cohorts of mice.
Among others, Taconic offers its C57BL/6NTac mouse, a standard background for genetically modified models and the genetic background of a considerable number of KO mice produced for phenotyping by IMPC. This partnership will allow IMPC to gain information and access to Taconic’s capabilities in generating study ready cohorts of mice from ES cells, as well as advanced embryology services and breeding support, drawing on its 60-year history as a leader in mouse breeding.
See enclosed document for further information on the partnership and Taconic.
The International mouse Phenotyping Consortium (IMPC) would like to welcome input from and form partnerships with the private sector. We seek to engage with industry at several levels - Institutional Membership, Corporate Sponsorship and Corporate Partnership. The IMPC currently comprises 16 Research and 6 Funding members, and together makes a substantial customer base and opportunity for scientific synergy with industry. We request any interested parties submit proposals to the IMPC for consideration. For more information please see the attached document.
Professor Steve Brown of MRC Harwell has been elected Chair of the IMPC for a second term. Steve Brown led the successful Eumodic project which was funded by the European Commission as pilot for the IMPC. He is Director of the MRC Harwell which is a leading international centre for mouse phenotyping. He also heads a research group investigating the molecular genetics and pathobiology of deafness.
Steve Brown said, “ I am delighted to continue as chair of the IMPC. We had had a successful first year and have extended the number of full partners of the IMPC to sixteen. The phenotyping pipelines are in operation at many of the centres and phenotyping of the first lines is nearing completion. During this next year we hope to attract more members to IMPC and increase the output of fully phenotyped lines.”
On 29th June, Prof. Luigi Nicolais, President of CNR (Italian National Research Council), authorized the plans to initiate the construction of the CNR EMMA-International Monterotondo mouse clinic. The Monterotondo mouse clinic (MMC), supported in Italy by both CNR and ISS (Italian Higher Institute of Health), is a member of the International Mouse Phenotyping Consortium (IMPC) and plans to participate in the generation of mutant mice from the International Knockout Mouse Consortium (IKMC) mouse mutant resource, followed by broad based primary phenotyping. The IMPC expects the ongoing programme to provide new insights into mammalian gene function and to be a major source of novel models of human disease, providing substantial information on the underlying genetic mechanisms of disease processes. As well as contributing to the IMPC programme, the MMC will be a centre for Italian scientists to access expertise in mouse phenotyping and the identification of novel disease models.
Prof.Glauco Tocchini-Valentini said:
“ The Monterotondo mouse clinic represents an important step in the involvement of Italy in the International Mouse Phenotyping Consortium. The MMC will act as a major centre both to deliver our contribution to the IMPC, but also to help Italian scientists with the identification of new disease models, playing a vital role in the wider biomedical science community.”
An international project to create one of the largest libraries of mammalian genetic function data is to be launched on 29th September 2011.
The International Mouse Phenotyping Consortium (IMPC) is building a library of mammalian gene function which will describe the function of every gene in the mouse genome. Around 99 per cent of the genes in a mouse have an equivalent gene in humans. By understanding the function of all the genes within the mouse, scientists can improve their understanding of the role that genes play in human diseases such as heart disease and diabetes.
The IMPC programme will allow researchers from across the world to easily access all of the resources and information created by the programme on `knockout mice` - that is, mice in which scientists have inactivated (or `knocked out`) a gene in order to discover what that gene does. This will substantially shorten the time between basic research and clinical application. Dr Mark Moore, IMPC Executive Director, explains: "We want to characterise each line of mice broadly with no assumptions about what the gene may be doing."
"If you think of the function of a gene as a needle in a haystack, we`re removing the haystack so scientists can see what the needle does," he added.
The IMPC is a worldwide consortium comprising fifteen research institutions along with national funders from six countries, including the Medical Research Council (MRC) Harwell (UK), the National Institutes of Health (US), the Wellcome Trust (UK), the Wellcome Trust Sanger Institute and EMBL-European Bioinformatics Institute in Hinxton (UK), Helmholtz Zentrum München, German Mouse Clinic (Germany), Toronto Centre for Phenogenomics (Canada), Institute Clinique de la Souris (France), Australian Phenomics Network (Australia), RIKEN BioResource Centre (Japan), CNR Monterotondo (Italy), Baylor College of Medicine (US), University of California Davis (US), Charles River Laboratories (US), Children`s Hospital Oakland Research Institute (US), the Jackson Laboratory (US), Genome Canada (Canada), MARC Nanjing University (China) and Canadian Institutes of Health Research (Canada). This strong international partnership hopes to increase its membership as the programme moves forward.
"Our drive is to understand the role of genes in disease and use that understanding to improve healthcare," explains Dr Bill Skarnes, Senior Investigator at the Wellcome Trust Sanger Institute. "The cells and DNA resources we have developed for IMPC have already proved their value in identifying genes involved in a form of anaemia. The integrated resources delivered by IMPC will make a real difference to researchers' work around the world."
Funding has been awarded to members of the consortium by a number of national funding agencies. Recently, several members of the consortium have been awarded US $110m over five years by the NIH to work on the project; which includes the Knockout Mouse Phenotyping Project 2 (KOMP2) and MPI2. The first phase of this ten-year project will knock out 5000 mouse genes and describe their physical characteristics or phenotypes.
Each mutant will pass through a series of examinations similar to the examinations patients might experience at a doctor`s surgery or in hospital to diagnose their condition. All members of the IMPC will use standard agreed procedures to perform the biological investigations and the data will be deposited in a single international database. The set of tests is designed to give information on human disease, such as heart disease, diabetes, and deafness, and the results will determine if that gene has a part to play in those diseases. The mice and the data generated from them will be freely available to the scientific community.
Dr Francis Collins, Director of the NIH, says: "The addition of detailed clinical information for each knockout mouse line will be a boon to disease researchers who want to determine the function of genes and improve mouse models of human disease."
Professor Steve Brown, Director of MRC Harwell and Chair of the IMPC Steering Committee says: "The launch of the IMPC represents an outstanding example of international cooperation in the biomedical sciences. IMPC is an unprecedented and unique international biological research endeavor that brings together diverse expertise and facilities to tackle the enormous challenges of understanding the relationship between gene and disease. This latest funding boost from NIH along with the funding available from other funding agencies means the first phase of the project is on track."
Professor Martin Hrabé de Angelis of Helmholtz Zentrum München and coordinator of Infrafrontier, a world class pan European research consortium for systemic phenotyping and archiving of mouse models, says: "This is an outstanding and unique opportunity to leverage existing know how and infrastructures in different continents by running a so far unmatched global programme to unravel gene functions of human diseases."
Data generated by the IMPC will be used by pharmaceutical and biotechnology companies to speed-up the development pipeline of new drugs. Dr Tom Weaver, Director of the MRC Mary Lyon Centre which is one of the IMPC production and phenotyping centres, explains: "There are literally hundreds if not thousands of drug targets that have yet to be discovered. The application of mouse genetics in combination with phenotypic analysis is recognized as an essential method for identifying and validating drug targets and drugable pathways. They will serve as tools to understand the mechanisms of action of drugs in vivo, and efficacy testing prior to expensive clinical trials."
Underpinning the IMPC project has been a lengthy period of planning and technical preparations. A fundamental component of this has been the planning for a data coordination centre (DCC) which will allow unrestricted public access to IMPC data. Dr Ann-Marie Mallon, Head of Informatics at MRC Harwell explained "We are committed to make data from IMPC public in an accurate, timely, and intuitive manner to ensure any institution or researcher around the world can access this data and the genetically modified mice".
Dr Paul Flicek, of EMBL-EBI, added: "The open resources created by IMPC will be integrated with many other molecular databases at EMBL-EBI and elsewhere, and benefit from advanced search functionality. This will ensure that researchers can make use of detailed data and high-level summaries of mouse phenotypes and other relevant biological information - for example human disease associations - well into the future."
The IMPC is building on the successful and ground-breaking EUMODIC project (funded by the European Commission under grant LSHG-CT-2006-037188) which developed the SOPs and IT systems needed to store the vast amounts of data generated and piloted the production and phenotyping of the mice. IMPC is therefore building upon years of planning and technical preparation.
NIH to make a mightier mouse resource for understanding disease ($110 million funding announced), September 29, 2011 News Release - National Institutes of Health (NIH).
We are pleased to announce the appointment of Dr. Mark Moore as Executive Director for the International Mouse Phenotyping Consortium. Mark brings extensive experience in mouse genetics and mouse phenotyping from industry and the IMPC Steering Committee are delighted to have him on board. Mark worked at Genentech in the early 90's where he used gene knockouts as drug discovery and validation tools. His work included the potential targets Her2 and Vegf, and his work helped in the development of the blockbuster cancer drugs Herceptin and Avastin. Mark subsequently founded Deltagen whose mission was to perform high throughput gene targeting and phenotyping to discover novel drug targets; under his direction, the company reached an output of over 250 lines per year. For the past 6 years, he has worked as a Senior Consultant for the NIH (US) on the Knockout Mouse Project (KOMP). We believe that Mark's background and enthusiasm for the IMPC make him an excellent fit, and we look forward to his taking forward the plans of the IMPC and working with the international community to bring to fruition the goals and ambitions of the consortium.
A report distilling the conclusions of the Industry Workgroup meeting is available to download.
A report distilling the conclusions of the Phenotyping Workgroup meeting is available to download. We are seeking feedback on the reports conclusions and it is possible to post comments to the IMPC website.
A meeting to discuss IMPC-Industry collaboration will be held on April 7, 2011 at the Wellcome Trust, London, UK. Participants include representatives from Pharma, Biotech, Mouse Vendors and CROs, Platform and IT Providers, Academic and Government Research Organizations, Tech Transfer Officers and Specialist Consultants. Visit the Industry Work Group section.
A report distilling the conclusions of the Phenotyping Workgroup meeting is in preparation and will be posted shortly. We will be seeking feedback on the reports conclusions and it will be possible to post comments to the IMPC website shortly.
A group of internal and external experts discussed the ideal test systems available for many disease areas and how to best arrange them into a phenotyping pipeline.
A group of internal and external experts discussed the informatics requirements for the IMPC programme and was asked to investigate the likely costs for the funding agencies.
It was published in September 2010 with a deadline for submission on 10.11.2010
The Business plan was finished on 02.08.2010 and a revised version from 15.11.2010 can be downloaded from this website in the background section
NIH announced a $110M investment into IMPC in May 2010 at a meeting held at the Royal Society. Nature picked up on this and reported it online 25 May 2010 | Nature 465, 410 (2010) | doi:10.1038/465410a
