- Total grants
- Total funders
- Total recipients
- Earliest award date
- 10 Apr 2001
- Latest award date
- 07 Jun 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.
Cargo transport by dynein/dynactin 10 Apr 2018
Eukaryotic cells rely on motor proteins for their internal organization and movement. I want to ask how one cytoplasmic dynein, together with its cofactor dynactin, can be responsible for almost all of the minus-end directed microtubule transport in our cells. My group will focus on endosome transport as a model system to understand which adaptor proteins are needed to link dynein to cargos. We will use in vitro reconstitution and cryo-EM to ask how different candidate adaptors interact with dynein/dynactin. We will also use structural approaches to understand how the different adaptors are themselves linked to membrane surfaces. To complement this approach we will purify endosomes and use cross-linking and mass spectrometry to search for any missing components required for dynein binding. We will take advantage of recent advances in cryo-electron tomography (cryoET) to ask how dynein/dynactin complexes and their associated connections are arranged on endosomes, both in vitro and in axons of cultured neurons. These studies will uncover the principles governing dynein/dynactin interactions with cargos and will allow us to ask how the process can be hijacked by pathogens such as herpes or rabies viruses.
We know surprisingly little about the basic logic, topology or origins of eukaryotic cell architecture even though such an understanding is fundamental to most biomedical research. Until recently, the proteins responsible for shaping eukaryotic cells (including Actin/Tubulin/coatamers/ESCRTIII) were thought to be unique to eukaryotes. This changed with the discovery of close homologues in TACK/Loki-family archaea. Despite the important part played by these proteins during eukaryogenesis, we know little about their functions in the context of archaea. To determine how these cytoskeletal systems with origins in archaea contributed to the emergence of internal compartments that define eukaryotes, our team will use metagenomic sampling and phylogenomics to trace their evolutionary history, and a combination of approaches, including live super-resolution microscopy and electron tomography to carry out a comparative analysis of their ultrastructure, dynamics and function in both archaea and eukaryotes. Ultimately, we expect this evolutionary cell biological analysis to make a start towards an understanding of archaeal cell biology, to reveal the likely path of eukaryogenesis, and to reveal underlying principles of eukaryotic cell biology that so far have eluded us. In doing so, we expect this fundamental research to have a signficant impact in the future on human health and disease.
Neural circuits underlying parental behaviour. 19 Nov 2014
The aim of my proposed research programme is to uncover the neural circuit logic underlying parental behaviour. Galanin-expressing (Gal+) neurons in the medial preoptic area (MPOA) were recently shown to control parental behaviour in male and female mice. At the initial stage of the project I will trace the axonal projections and presynaptic partners of MPOA Gal+ neurons and characterize the input-output relationships and functional diversity of this population in both sexes (Aim 1). Subsequentl y, I will use optogenetic stimulation to investigate which MPOA Gal+ target areas control parental behaviour and whether different MPOA Gal+ neurons control discrete aspects of parental behaviour, such as pup retrieval, grooming or nursing (Aim 2). Finally, I will perform high-resolution functional mapping of parenting circuits in virgin males and fathers to reveal how social experience affects the structure and function of these circuits (Aim 3). These experiments aim to obtain a mechanistic un derstanding of parental behaviour at the level of neural networks.
Despite many years of study, the molecular mechanisms underlying several humansenses, in particular hearing, touch, and sour and salt taste, remain poorly understood. Each of these processes relies on ionotropic receptors that are directly gated by the sensory stimulus; however, the mechanisms underlying this gating, and in many cases even the identities of the the relevant receptor molecules, remain unknown. Recently, work from our lab and others has implicated members of the TMC family of putative ion channels as sensory receptors for taste and hearing[1,2]. In the planned research, we will characterize the in vivo roles and functional properties of worm and mammalianTMCs and determine how they respond to sensory stimuli. Since mammalian sensory receptors often retain functionality when heterologously expressed across phyla[2,3], we will use the genetic tractability of C. elegans to dissect functional domains of mouse and worm TMCs in an in vivo context. In addition, since known families of ionotropic sensory receptors are largely conserved in the worm, we expect that novel receptors with conserved roles in mammals can identified by worm genetics. We will therefore screen for novel ionotropic sensory receptors by highthroughput phenotyping of C. elegans mutants. Specific aims include: 1. Characterize the functional properties of mammalian and worm TMC proteins by heterologous expression in C. elegans neurons. 2. Investigate the relationship between TMC protein structure and function through analysis of chimeras and mutant proteins. 3. Using the information from heterologous expression studies, study the in vivo functions of mouse TMCs in knockout animals. 4. Identify novel sensory receptors by high-throughput phenotyping of C. elegans knockout strains.
Focussed ion beam and scanning electron microscope for 3D reconstruction of large volumes in neuro- and cell biology and nano engineering of electron cryotomography samples. 25 Jun 2014
We are proposing to acquire a FIB/SEM dualbeam instrument at the MRC Laboratory of Molecular Biology in Cambridge (LMB). LMB will provide dedicated, newly fitted-out facility space, staff support, a service contract and half of the instrument cost. Access of the wider community is ensured through the inclusion of Cambridge University's imaging centre and our dedication to make up to 30 % of time available to outside users. The focussed ion beam (FIB) is exceptionally useful for the removal of ma terial from samples for subsequent electron microscopy, at sub 5 nm resolutions not achievable by any other means. The machine will have two principal uses: firstly, the FIB will be used to serially remove very thin layers from large blocks of embedded tissues, with the electron beam producing images of each layer. This will allow automatic three-dimensional reconstruction of large volumes of whole tissues, making it possible to trace neurons and their connections or sub-cellular membrane domain s (FIB/SEM 'slice-and-view'). Secondly, milling of samples for electron cryotomography will enable us to visualise the interior of cells at isotropic resolutions approaching individual molecules and this application of the instrument will make heavy use of LMB's recent investment in high-resolution electron cryomicroscopy.
RNA-binding proteins in health and disease. 10 May 2011
Our research focus on the role of RNA-binding proteins (RNABPs) in gene expression at different levels during the RNA processing cascade from splicing in the nucleus to translation in the cytoplasm. RNAs in cells associate with RNABPs to form ribonucleoprotein (RNP) complexes. There is a great variety of RNABPs, each with unique RNA-binding activity giving rise to a unique RNP for each RNA. They have a profound impact on cellular gene expression networks, affecting processes as diverse astranscription, pre-mRNA splicing, microRNA (miRNA) biogenesis and function andtranslation.
Investigation of the PTB-dependent RNA operon that regulates cytoskeletal organisation and cell migration. 14 Jun 2010
Messenger RNAs are subject to post-transcriptional control by a number distinct of mechanisms. Expression of the corresponding proteins can be regulated by changes in the rate of the mRNA degradation, and by transport of the mRNA to a specific cellular location. Cytoplasmic post-transcriptional control is tightly regulated by defined groups of mRNA binding proteins and it has been suggested that specific RNA-operons , comprised of RNA motifs and their cognate RNA binding proteins, ensure co-r egulated synthesis of proteins with common functions. To define the PTB-operon we have carried out polysome profiling following a reduction in PTB expression in conjunction with RNA co-immuno-precipitation using a PTB specific antibody to identify the mRNAs that bind to PTB and/or are dependent upon this protein for efficient translation. Approximately 25% of the mRNAs identified by these screens have a role in cytoskeletal organisation/cell migration. Our data suggest that PTB controls both the translation and the localisation of these mRNAs. The overall aims of this project are to identify the RNA elements and the proteins (in addition to PTB) that comprise the PTB operon and are involved in the post-transcriptional regulation of mRNAs that have a role in cytoskeletal organisation and cell migration.
Auxiliary factors for microRNA processing. 31 Oct 2007
We have discovered the existence of auxiliary factors for miRNA processing. Here, we will investigate the mechanism by which hnRNP A1 facilitates the Drosha-mediated processing of miR-18a. We will investigate how the abundance of hnRNP A1 correlates with miR-18a expression and influences the regulation of miR-18a mRNA targets. More importantly, these experiments should shed light on what makes a particular miRNA require an auxiliary factor for its processing. We aim to identify other miRNAs that require hnRNP A1 for their processing and to define the generality of RNA-binding proteins as auxiliary factors for miRNA processing.
Structural and functional analysis of interactions involving the nuclear transport machinery that generate nuclear RNA and protein export and orchestrate mitotic spindle assembly. 01 Nov 2006
My overall goal is to understand how nuclear transport factors interact with their cargoes and other components of the transport machinery to (i) export macromolecules from the nucleus during interphase and (ii) orchestrate spindleassembly during mitosis. These aims share a common focus on nuclear transportfactors and their interaction with different partners, and build on my previous work that established the structural basis for key steps in the nuclear protein import cycle. Molecular recognition by transport factors is fundamental to the nuclear export of proteins, mRNA, pre-microRNA, and tRNA, and is also crucial in mitotic spindle organization. My primary goal is to usethe interdisciplinary approach I developed for studying nuclear protein import, in which structural, biochemical, molecular and cellular methods will be used in concert to investigate the key complexes involved in each process and establish interaction interfaces. This information will then be used to define how each function is generated by a precisely orchestrated series of interactions, employing structure-based engineered mutants that alter specificinteractions. These mutants will be used to establish the spatial and temporalpattern of interactions that generate function and so enable these important cellular processes to be understood at the molecular level.
Type 1 diabetes is considered a Th1 mediated disease. Recently the role of Th1T cells in a number of autoimmune diseases, notably EAE and arthritis, has been questioned, since it became clear that the principal effector cells in these diseases are a novel subset of CD4 T cells, termed Th17 T cells, which as we have recently shown differentiate from naïve precursors in response to acombination of TGFb1 with IL-6, further amplified by TNFa and IL-1b?. Th17 T cells and Th1 T cells are mutually inhibitory and any differentiation step that favours the development of Th17 will compromise generation of Th1.The involvement of IL-17 in diabetes has so far not been addressed and there are observations that suggest Th17 might not be pathogenic in diabetes and that onthe contrary their induction at the expense of Th1 might be beneficial. We will attempt to causally link the protective effect of immune modulators such as schistosome egg extract and zymosan to differential activation of DC that would favour the development of Th17 at the expense of Th1 cells and predict that Th17 cells do not cause pathology in diabetes, but may rather interfere with pathological Th1 responses.
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.