Consortium Groups list

Principal Aims and Objectives: 

The MRC Mouse Network has been created in order to provide UK scientists with a forum to engage with a new and exciting international program systematically mutating every gene in the mouse genome and determining the resultant phenotypes of the mouse lines - the International Mouse Phenotyping Consortium or IMPC (www.mousephenotype.org).

All scientists are welcome to join the MRC Mouse Network where you will receive regular updates about access to

  1. MUTANT MICE a steadily growing collection of strains which are multifunctional in terms of their application to genetic research (eg null alleles, reporter gene expression, conditionality)
  2. PHENOTYPIC DATA from a variety of therapeutically relevant systems collected for each mutant strain (primary phenotyping data)
  3. COLLABORATIVE RESEARCH & TRAINING opportunities between members of the network, where we encourage scientists carrying out basic or clinical research in academia or industry to take this opportunity to advance their research programs.
Principal Aims and Objectives: 

Aim: Capitalising on data provided by IMPC to further investigate a selected group of genes in mouse important in six key areas of disease-related neuroscience research: (1) ion channels and epilepsy, (2) mitochondrial disease, (3) neurodegeneration, (4) neuromuscular diseases, (5) neuropsychiatric disease, (6) sensory systems.

This aim will be achieved by a well-organised integrated group of basic scientists and clinicians, with input from human geneticists, who have outstanding track-records in working with mouse models to understand human disease. This highly experienced group will take data from a carefully selected list of genes/mutants and pursue investigations that arise from the novel information provided by IMPC/MRC.

To achieve a successful outcome (as measured by new collaborations and insight, as well as conventional metrics such as publications and grants) we have six objectives:

  1. A clear organizational structure that integrates key researchers.
  2. Scientifically and clinically insightful selection of candidate genes.
  3. Extending findings in our specific research areas, based on IMPC data and our existing expertise and facilities.
  4. Integration and discussion of results across all Consortium member laboratories for novel insight into different research themes.
  5. Future research and applications arising from the initial Neuromouse Consortium bid.
  6. Transformative science with translational impact to tackle human neurological disorders.
Principal Aims and Objectives: 

Amongst all of the body systems that can be accessed for the description of phenotype, myeloid cells of the innate immune system are unique in that it is practical to obtain them in large numbers from stored bone marrow progenitors. We aim to establish an in vitro screening panel to investigate the effect of a large number of gene-knockouts on innate immunity, leading to functional annotation of the mouse genome.
Objectives:

  • Establish an in vitro screening panel to examine the impact of knockouts on myeloid differentiation, innate immunity and antigen presentation
  • Identify the functions of a large number of genes (>20% of total protein coding genes) expressed specifically in cells of the innate immune system
  • Identify the function of a large number of genes involved in more general cell functions (proliferation, apoptosis, cell motility)
Principal Aims and Objectives: 

The overall aim of this proposal is to establish mouse disease models for human bone and cartilage disorders that include osteoporosis, osteoarthritis, skeletal trauma, chondrocalcinosis, Paget’s disease and skeletal dysplasia that will help to elucidate the underlying biological mechanisms and provide in vivo models for pre-clinical studies. Thus, our consortium will have a world-leading impact in the development of novel approaches for the prevention and treatment of the major diseases of bone and cartilage.
Objectives:

  • Establish mouse models of bone and cartilage disorders
  • Characterise the phenotypes and pathophysiology, using established high-throughput primary and secondary phenotyping platforms (including: dual-energy X-ray absorptiometry (DEXA) and faxitron and quantitative digital X-ray analysis of bone mineral content, ; 3D and micro CT analysis of bone structure and bone mineral density (BMD); in vivo fluorescent imaging; high resolution MRI; biomechanical characterisation of bone in bending and compression of fracture analysis; histological assessments; and clinical chemistry). The consortium will work with MRC Harwell to develop and improve where possible the primary phenotyping pipeline.
  • Make use of these models to elucidate underlying biological mechanisms, develop biomarkers and facilitate translational research
  • Evaluate translation of findings to the human population level by comparison to large scale GWAS datasets (GEFOS and TREAT-OA)
Principal Aims and Objectives: 

To accelerate drug discovery through the use of mouse knockout models, beginning with the ubiquitylation system. The UK-China network will bring together academic, governmental, and industrial researchers who are experienced and committed to applying mouse models towards developing innovative new medicines. The network will focus on generating and phenotyping knockout mice for genes of the protein ubiquitylation system.
Objectives:

  • Prioritization of ALL genes of the deubiquitylases, E2 conjugating enzymes, F-Box substrate targeting subunits of cullin containing E3 ligases and HECT E3-ligases – The first systematic screen of this novel class of drug targets.
  • 100 GLT knockout Mice with phenotypic information – China and UK will contribute equally to the production and analysis of mutant strains (50 strains each), doubling output.
  • Discover novel 3D structural information of candidate targets by crystallizing a significant number of DUBs and HECT type E3 ligases.
  • Advise and interpret results from the phenotyping pipeline - Regular scientific and operational feedback from renowned experts, including the Nobel prize winning discoverer of protein ubiquitylation, will ensure optimal effectiveness and value of the screen.
  • Promote translational studies to increase value of the MRC IMPC program - Partners will use the strains and associated information to advance their own research programs.
  • Novel phenotypes discovered through these KOs could point to disease association and previously unrecognised targets for drug discovery.
  • Supplemental funding will be secured and used to expand and exploit the MRC IMPC program.
Principal Aims and Objectives: 

The primary goal of the UK GoLD consortium will be to translate genetic association into a mechanistic understanding of the pathogenesis of liver disease and onwards to the identification of novel therapeutic targets. The UK GoLD Consortium will focus on three areas: (1) Mechanisms of Addiction Behaviour – an initiator of liver disease risk; (2) Mechanisms of Metabolic Liver Disease (e.g. Non-Alcoholic Fatty Liver Disease), Inflammation and Hepatocellular Injury; (3) Modifiers of Hepatic Fibrosis Progression and Liver Regeneration.
Objectives:

  • To identify genes that confer susceptibility to risk behaviours and determine disease severity
  • To understand mechanisms by which genes & gene-environment interactions cause disease
  • To validate GWAS and candidate gene associations through translational research
  • To identify and exploit novel potential therapeutic targets.
Principal Aims and Objectives: 

We aim to use mouse models to define early events associated with neurodegenerative disease and ageing, thereby identifying intervention strategies to prevent cognitive decline and disease progression in humans.
Objectives:

  • Identify key genes and proteins involved in triggering neurodegeneration in vivo
  • Examine contribution of neuronal, synaptic and glial dysfunction to neurodegeneration
  • Identify phenotypic biomarkers of cognition and behaviour capable of reporting and tracking neurodegeneration
  • Investigate the impact of stress, infection and age on neurodegenerative processes, including their role as precipitating factors
  • Elucidate the extent to which common and distinct molecular mechanisms underlie the early stages of a range of neurodegenerative diseases
  • Identify strategies for blocking neurodegenerative processes, particularly before overt pathology occurs
Principal Aims and Objectives: 

The aim of the Respiratory development and disease consortium is to utilize mice obtained through the IMPC to generate novel in vivo models of respiratory disease and to further the existing research programs of participating P.I’s and the wider respiratory research community.
Objectives:

  • To explore resilience to disease and degeneration, understanding how it may be exploited for new interventions that ameliorate disease processes
  • To advance knowledge in the biology of aging and degeneration of human tissue
  • To understand the mechanism and impact of chronic inflammation
  • To translate burgeoning knowledge in regenerative medicine into new treatment strategies
Principal Aims and Objectives: 

We aim to understand the molecular determinants of nutrient sensing and energy balance (homeostatic and hedonic control of food intake, energy expenditure, nutrient utilisation and partitioning, adiposity and body composition); to determine how alterations in these pathways can lead to obesity, diabetes and associated metabolic complications; to advance understanding of the pathogenesis of Type 2 diabetes through characterisation of mechanisms involved in beta-cell dysfunction and insulin resistance; to identify and develop specific therapeutic approaches that could prevent or reverse obesity, diabetes and associated metabolic complications.
Objectives:

  • Nominate for priority targeting and phenotyping candidate genes that are not only highly relevant to obesity and diabetes research based on genetic, genomic, functional, and literature evidence but also have translational potential
  • Provide advice for the primary phenotyping of these animal models at MRC Harwell. The MODO consortium will link with MRC Harwell to maximise the likelihood of relevant metabolic characteristics becoming manifest and detected
  • Capitalise on these primary data by planning/undertaking more detailed secondary phenotyping studies through a collaborative network incorporating MRC Harwell and selected academic groups in the UK with demonstrable track records in metabolic research in rodents and humans. These groups will use shared protocols and approaches to secondary phenotyping to ensure standardization between centres. The MODO consortium has the capacity to optimise the information obtained from selected GM models through our in vivo, cellular and molecular phenotyping expertise, guided by our strengths in human genetics and metabolism.
Principal Aims and Objectives: 

The aim of the consortium is to improve our understanding of normal and malignant haematopoiesis, with the particular goal of identifying genes and pathways that control the development and homeostasis of the normal haematopoietic system, as well as genes that cause and modify malignant haematopoietic syndromes.
Objectives:

  • To pass mouse lines of interest through a secondary phenotyping platform designed to complement the IMPC pipeline and detect relevant genes that would otherwise be missed (exp. ~20 lines of interest)
  • To develop two tertiary phenotyping platforms (normal and malignant haematopoiesis) for further examination of interesting lines (exp. 3-5 lines through each platform)
Principal Aims and Objectives: 

The aims of the consortium are to facilitate directed phenotyping of mouse models within four themes of renal and urogenital dysfunction: glomerular, tubular, developmental, and cystic. Cross-theme interactions will be encouraged to identify pleiotropic effects (renal and systemic) of targeted genes. The development of systems permitting ready dissemination of data will, therefore, be prioritized, so that each individual member can draw on the wider expertise of the consortium. This will be of particular importance, because it is anticipated that individual genes will influence multiple renal phenotypic traits.
Objectives:

  • To establish theme-based steering committees and develop methods for intra-network communication
  • To develop robust experimental procedures for sample collection/handling and data analysis/storage
  • To plan the extension of the GUDMAP database (see CV of Prof. Jamie Davies) for network data curation, and identify routes for core and response mode funding
  • To host a network strategy meeting in London (which would be the responsibility of the lead coordinators to organize and fund) to meet these objectives
Principal Aims and Objectives: 

The aim of our consortium is to functionally characterise a series of new mouse models for candidate genes derived from human GWAS studies (BP and ECG traits) and functional experimentation (LVD, HF and CAD). The traits we have selected represent the research activities of the applicants, many of whom are regarded as world leaders in their field. Development of novel treatment strategies is hindered by the limited number of potential targets for treatment. Thus there is an urgent need to elucidate novel aspects of basic pathophysiology of hypertension, cardiac arrhythmias and HF. The results of such studies will likely facilitate innovative drug development aimed at preventing these traits and will improve prognosis.
Objectives:

  • To establish whether the KO mouse has the CV phenotype we predicted based on the reason for selecting the gene
  • To establish additional phenotypic deviations from normal, including target-organ damage (heart, brain, kidney)
  • To generate detailed characterization on the functional consequences and pathways affected by the absence of the KO gene
Principal Aims and Objectives: 

Fibrotic diseases are a leading cause of morbidity and mortality and are relatively intractable to current treatments. The response of any organ, to tissue damage involves a carefully choreographed series of cellular interactions between immune (haematopoietic) and non-immune stromal cells. Therefore understanding the effect of modifying the biology of leukocytes, endothelium or fibroblasts in terms of their effect on tissue fibrosis is a vital area of research. The aims of this consortium are to define the critical regulatory networks underlying the pathogenesis of organ/tissue-based fibrosis and tissue remodelling processes, delineate the cellular and molecular links between tissue injury, subsequent remodelling and the development of fibrosis, and to identify organ-selective and common anti-fibrotic targets. By combining are expertise we will utilise novel gene knockout mice to discover and develop novel therapies for the treatment of fibrotic diseases translating our findings into the clinical arena to enhance patient management and treatment.
Objectives:

  • Utilise a panel of gene knock-out mice generated by IMPC to determine molecular mechanisms initiating spontaneous fibrotic pathology in a range of different tissues using histopathology
  • For each gene knock-out mouse line utilise at least one in vivo model of fibrosis initiated by either tissue injury, infectious disease (viral, bacterial or parasitic), surgical manipulation, autoimmune disease, wound healing, cardiovascular and pulmonary inflammation or chemical administration to study the influence of gene deletion in different organs and tissues
  • Utilise an integrated research approach combining systems biology approaches with primary human tissues, experimental mouse models and the gene knock-out mice to discover and define pathways underlying the pathogenesis of fibrosis and tissue remodelling
  • Where appropriate apply cutting edge image analysis to understand cellular process involved in tissue fibrosis in gene knock-out mice
  • To adopt conditional allele deletion to refine our understanding of leading candidate genes in fibrosis and tissue remodelling using tissue specific, temporal or cell specific Cre recombinase mice to micro-dissect the pathogenic process
Principal Aims and Objectives: 

We are aiming to identify the pathways that underlie normal eye function and how these are disrupted in disease as well as providing platforms for therapeutic developments. This will be done by generating mouse models of human vision and eye disease for investigation of disease mechanisms and therapies.
Objectives:

  • To organise collaborative meeting in early 2012 to prioritise genes and models in the pipeline
  • To establish phenotyping infrastructure at each centre
  • To process lines in parallel in collaborative centres, depending on disease model
  • To attract additional EU funding
Principal Aims and Objectives: 

The Developmental Anomalies Consortium aims to identify, develop and analyse the IMPC mouse models of congenital malformations (birth defects) in order to understand the development of birth defects affecting a range of organ and other body systems in the mammalian embryo and fetus, and establish tools (e.g. biomarkers, bioactive molecules, nutritional supplements) that could be translated into clinical diagnosis, therapy and prevention of human birth defects.
Objectives:

  • To analyse tissue and stage-specific gene effects using Cre-deleter strains and, where relevant, to evaluate gene-environment interactions (e.g. effect of nutritional folate deficiency)
  • To refine our understanding of the pathways in which the genes operate with extension to downstream regulated genes (e.g. via transcriptome analysis)and upstream regulatory mechanisms
  • To use the mouse models to develop biomarkers and therapeutic interventions that could test hypotheses on the mechanism of birth defect development in the model system and potentially be translated into novel clinical diagnostic or treatment initiatives
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