- Total grants
- Total funders
- Total recipients
- Earliest award date
- 10 Apr 2001
- Latest award date
- 30 Sep 2018
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Grant awarded to Community Service Volunteers (Training and Enterprise NE) (Tyne & Wear) 10 Mar 2009
To provide support and mentoring to people with mental health problems to help them volunteer in Newcastle.
Grant awarded to Community Service Volunteers (Training and Enterprise NE) (Tyne & Wear) 13 Jul 2004
To provide daycare services to older people living in high rise flats in Newcastle.
Positive Futures London 18 Nov 2015
This project, based on a established youth-led volunteering model is expanding as a result of self-referrals and is being delivered in Hackney, Haringey and Tower Hamlets. It will support young people aged 13 to 25 to deliver volunteering and social action projects which they have identified to be of benefit to the local community. The aim of project is that all of the young people who are participating in it will develop key skills and have positive experiences that will shape their personal development.
An Extended Pilot for the Human Cell Atlas: Adult tissues, human development and inflammation-mediated pathologies 30 Sep 2018
The Human Cell Atlas (HCA) is an international, collaborative effort that "...aims to define all human cell types in terms of their distinctive patterns of gene expression, physiological states, developmental trajectories, and location". Here, we will contribute directly to the first phase of the HCA by forming an ‘extended pilot’ to implement UK infrastructure for large-scale, high quality human cell atlas experiments. We will generate a high-level atlas, with spatial resolution, for multiple adult human tissues along with matched data from human fetal material. We will then illustrate the power of a deep and focused investigation of a single tissue (skin) to produce highly-detailed data describing its cellular composition and spatial organisation. Finally, for selected tissues that have been profiled in adults and fetal material, we will analyse samples from immune-mediated disorders as a comparison with our reference data to gain deeper understanding of the pathological mechanisms. This will demonstrate the utility of the HCA as a ‘healthy reference’ for comparison with disease. Throughout, we will generate profound biological insight from primary human cells and lay a foundation of technology development and optimisation with a set of hardened and scalable methods for single-cell RNA-sequencing, spatially-resolved gene expression, and tissue imaging.
Origins of bone and cartilage disease. 17 Apr 2013
In a pilot study of 100 knockout mouse lines we developed a rapid-throughput skeletal phenotyping platform and identified nine new genes with diverse, unrelated and unpredictable functions that determine bone mass and strength. We hypothesise that large-scale phenotyping of knockout mice will identify novel susceptibility alleles for bone and joint disorders and genes that underpin skeletal physiology. Thus, we will extend our platform to identify phenotypes affecting cortical and trabecular b one structure and strength in female mice from 1160 knockout lines generated by the Wellcome Trust Sanger Institute (WTSI) Mouse Genetics Project. In parallel, we will validate a rapid-throughput screen to identify abnormalities of joint morphology, articular cartilage integrity and subchondral bone mineralisation in male mice. Comprehensive studies in selected mutants will incorporate (i) disease-provocation models to determine whether gene deletions affect the onset or progression of bone lo ss and cartilage destruction, and (ii) transcriptome analyses to identify gene networks that control skeletal development, maintenance, and function. Collaborations with international consortia studying bone density, fracture and osteoarthritis in human populations will translate gene identification to human disease. Rapid dissemination of annotated data will be achieved through the WTSI and a new Origins of Bone and Cartilage Disease website.
Two major limitations of single cell genomics is (i) the loss of information about the original location within the sample of the sequenced cell and (ii) low throughput at high cost with only hundreds of cells analysed per day. Miniaturising single cell analysis to pico-litre volumes will critically facilitate higher throughput (10^4 - 10^6cells) at lower costs and sidesteps restrictions in handling. Combined with genetic technologies to record lineage history and spatially localise cells this w ill allow questions to be address at single cell resolution that are essential to understand cell diversification following tissue-contextual interactions and the impact it has on gene transcription. 1) We will develop microfluidics based devices to increase sequencing throughput by increasing the number of cells processed at a low cost, and at the same time enabling the complex handling and manipulation of small cell numbers with minimal loss. 2) We will develop genetic technology to: i) record within the genome the lineage history of each cell, for readout at any stage of interest and ii) to provide a unique fluorescent signature to cells to enable us to provide spatial and temporal context to their transcriptional profiles.
Exploring the biological processes underlying mutational signatures identified in cancers. 20 Nov 2012
Somatic mutations in cancer genomes have been generated by multiple DNA damage processes, the effects of which may have been mitigated by the cellular repertoire of DNA repair mechanisms. Each process will leave a characteristic imprint, or mutational signature, on the cancer genome. Our understanding of these signatures and their underlying mutational processes is remarkably limited. The overarching theme of this proposal is to explore the biological basis of mutational signatures that emerge f rom sequencing whole cancer genomes. The first aim is to systematically manipulate components of the DNA repair/replicative machinery in model systems, by targeted disruption or over-expression, followed by re-sequencing of clones to define genome-wide mutational signatures generated by these engineered abnormalities. The second main aim is to establish a resource of induced pluripotent stem cells (iPSCs) and/or lymphoblastoid cell lines (LCLs) from patients with naturally occurring germline defects in genes involved in DNA repair/replication to study mutational patterns in these patients. Thirdly, the large projected datasets generated from these experiments will require computationally demanding exploration and downstream analyses. Ultimately, experimentally generated datasets will be compared to mutational signatures extracted from large-scale sequencing of cancer genomes, giving us insight into the perturbations that happen during cancer development.
Generation and validation of isogenic TP53 knock-out AML cell lines for use in genome-wide drop-out screens 01 Apr 2016
Acute myeloid leukaemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed significantly for decades. To identify new therapeutic targets in AML, Dr Vassiliou's group recently performed CRISPR-Cas9 dropout screens and identified 492 AML-specific cell-essential genes, including several established anti-leukaemic drug targets and many novel therapeutic candidates. Going forward they will apply this technology to AML subtypes defined by particular somatic mutations. One subtype of AML is defined by TP53 gene mutations and is associated with an abysmal prognosis, with For this, I will design and test different gRNAs for their effectiveness in knocking-out TP53. Cas9-expressing MOLM13 and MV4-11 cell lines will be transfected (separately) with lentiviruses carrying TP53-targeting or control gRNAs. Pooled cells will then be single-cell-sorted and clones assessed for TP53 knock-out efficiency using qRT-qPCR and western blotting. The best clones will then be used for downstream genome-wide screens.
We will exploit the opportunities of the UK National Health Service to generate a national resource of human iPS cells and associated data. We will generate and bank lines from 700 healthy and 800 disease-associated individuals, optimising techniques for iPS cell production and quality control. Cells will be subjected to extensive analysis of genome, epigenome, gene expression and proteome. For cells from healthy individuals, in-depth analysis of inter-individual variability will provide an open access platform for association studies of cellular function, and for distinguishing pathological from physiological variation. Patient collections will be selected via an open call, focusing initially on well-characterised conditions, where a single genetic lesion underlies a pleiotropic clinical phenotype. To characterise cellular phenotype we will construct high throughput artificial microenvironments. We will evaluate cell death, differentiation, morphology and division and specific signall ing pathways. We will collaborate to produce protocols to differentiate iPS cells into disease-relevant cell types. These approaches will provide in vitro readouts of inter-individual variation and disease and a platform for gene correction and engineering specific mutations into different genetic backgrounds. Our proposal will give researchers in the UK and beyond access to iPS cells and technology linked to extensive genetic, cellular and clinical information.
Population genomics of the mouse. 06 Oct 2009
The mouse is the leading model mammal in genetics and biomedical research, yet little is known about how variation in its genome translates to variation in reproductive fitness. This is important because the fitness effects of nucleotide variants are closely related to the nature of quantitative genetic variation, such as susceptibility to genetic disease in humans. We propose to study the population genetics of Mus m. castaneus, a highly variable subspecies from the ancestral range of the house mouse subspecies complex. We shall generate accurate, whole genome nucleotide polymorphism data for the genomes of a sample of wild-caught individuals. Using this data in conjunction with the mouse genome annotation and the rat genome, we shall apply new methods developed by the PI and others that analyse within population polymorphism and between species divergence to infer the fitness consequences of nucleotide variation. We propose to estimate the frequency distributions of effects of new mu tations for both coding and noncoding DNA, and the frequency of adaptive substitutions in the genome. We shall analyse the spatial correspondence between selected-site divergence and neutral diversity to estimate both the rate and strength of selection associated with selective sweeps.
The Genomics of host adaptation in campylobacter 23 Jun 2009
A comparative functional genomics approach will describe the genetic basis and ecology of host specificity and niche adaptation in Campylobacter and how this relates to the emergence of virulence. Recent advances in Illumina GA resequencing technologies, specifically isolate multiplexing, enable high-throughput sequencing of multiple genomes and open the new field of population genomics . Large in-house isolate collections, genotyped at 7 loci, are the starting point for this multidisciplin ary fellowship studying the evolution and ecology of pathogens, in three major types of experiment: (i) Genome-wide association mapping in natural populations; (ii) Quantifying adaptability and generalism in in vitro experimental evolution systems; (iii) in vivo competition experiments in specific-pathogen free chickens. Genomic experiments will describe the mechanisms and nature of adaptations to host. The competition experiments will assay the absolute fitness differences of strains with diffe rent degrees of host-adaptation and allow rigorous tests of specific adaptive hypotheses. The laboratory experiments will help to elucidate variation in genome plasticity and its relationship to host adaptation. Experimental results will feed into the Genome Evolution by Recombination and Mutation (GERM) program, designed for this project to provide a systems approach to the investigation of niche adaptation and population structuring in bacteria.
Our goal is to understand how natural genome variation in human, Plasmodium and Anopheles populations affects the epidemiology and biology of malaria, and to use this knowledge to develop more effective ways of controlling the disease. This requires a concerted effort by many research groups around the world. We propose to establish a resource centre that will support this community effort by: - developing genome technologies and statistical methodologies to underpin global efforts to inv estigate genome variation in human, Plasmodium and Anopheles populations - building informatics systems and open-source web software for integrating and sharing large genetic and epidemiological datasets, to enable malaria researchers around the world to collaborate effectively to investigate how genome variation affects patterns of disease and biological phenotypes - providing scientific leadership in trans-ethnic genome-wide association studies of human resistance to malaria, and in de veloping a global system for monitoring Plasmodium populations by next-generation sequencing.
Community Healthy Living Advisor Volunteers 22 Jun 2006
The Manchester branch of Community Service Volunteers runs a range of projects that encourage people to take up learning via its Media Clubhouse. With this award it will deliver workshops, led by a qualified nutritionist, aimed at individuals who want to become volunteer healthy living advisors. The volunteers will be recruited from groups with multiple disadvantages as well as minority groups based in and around the City Centre.
Older people volunteering at primary schools 11 Jan 2005
The project will empower older people to take an active part in their communities by giving them the opportunity to take the lead in designing and delivering voluntary services to support the development of children in Hackney and Tower Hamlets. Older volunteers will work in primary schools to provide support for pupils, especially those for whom English is an additional language.
The project is a three day canoe camp for young people from an alternative curriculum Group. The money is for canoes, shelter and food and supervising staff costs.
Cole Haven 07 May 2007
This group will develop area of woodland located within the heart of Birmingham's inner city, and create an outdoor education available to local schools and the wider community.
This project works with parents and children aged 12-16 to help parents engage with and understand youth sub-culture through multimedia activities including film, radio, multi-media, music and arts projects. Issues of identity and behaviour will be explored by using 'Life Story' books, video diaries and talking families through a journey of their heritage.