- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 18 Jan 2019
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
LifeLines 20 Apr 2016
This is the expansion of a project supporting volunteers aged 50 plus to run activities for vulnerable older people to improve health and well-being. These have previously included art classes, creative writing, yoga and computer club. The group will expand across the city, recruiting more volunteers, supporting more than 800 new people and establishing a Menâ€™s Network to encourage older men to socialise regularly. It will also extend its HealthLink scheme to help older people get to medical appointments.
Kilkeel RBL - Saving Our Community Venue 22 Oct 2015
The group is a community and voluntary based organisation providing a range of services and activities to the local community. They received a grant of Â£10,000 to make improvements to their venue so that it can be used for more classes and activities.
Towards improving access and facilities for disabled people at the Forest Hall Ex-Servicemen's Institute.
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.
Dermatology and Genetic Medicine: A multidisciplinary research initiative aimed at translating basic science discoveries in genetic skin disease into clinical application. 17 Apr 2012
Dermatology is an under-resourced area of research, however, the University of Dundee has established a critical mass of internationally competitive researchers in genetic skin disease and cutaneous therapy development. This award will strengthen this multidisciplinary research centre and catalyze further clinically applicable research at the interface of genetics, dermatology and drug discovery. Specifically, a large collection of diverse monogenic disorders accumulated through a UK genoderma tology network will be analysed using whole exome sequencing approaches, informed by transcriptome analysis. Targeted sequence capture and next-generation sequencing of loci identified by genomewide association studies will discover new causative variants in eczema, in addition to streamlining analysis of the large, repetitive filaggrin gene. Our previous genetics work has identified a number of new therapy targets tractable by small molecule approaches, which will extended here. A profession ally-managed biotech-style cutaneous drug discovery portfolio will be developed (3 projects already initiated) and extended to run 15 high-throughput screens, supported by hit validation and early hit-to-lead chemistry, with the aim of taking at least 2 dermatology targets through to pharmaceutical partnering. Animal and cell-culture platforms for assessing cutaneous drug/siRNA delivery/efficacy will be established. This award will also strengthen our capacity for patient outreach and training of new investigators.
This bioinformatics research project will focus on the development of methods to predict the effects of non-synonymous single nucleotide polymorphisms on protein function. The project will evaluate current methods, develop a "meta-predictor" that combines the best methods and develop a new approach that includes data from recently published techniques in protein structure prediction and sequence analysis. The new predictor will be integrated with the Jalview multiple alignment workbench and be applied to novel whole exome and genome datasets produced by colleagues in Dundee.
Wellcome Trust Clinical PhD Programme at the University of Dundee: 'Development of novel models for the study of hepatic insulin resistance as a means to an early diagnosis and treatment for diabetes'. 11 Apr 2011
Reduced tissue sensitivity to insulin, called insulin resistance (IR), is a major feature of Type 2 Diabetes (T2DM). It also develops many years in advance before T2DM. The majority of the health problems associated with diabetes, such as vascular disease, are likely to begin to develop during insulin resistance. Therefore, it is important to understand why and how insulin resistance develops and how it progresses to diabetes and its complications in some people but not others. Insulin reduces hepatic glucose output in large part by repressing transcription of specific genes, but this process is defective in IR and T2DM. We will generate a transgenic mouse expressing a reporter peptide under the control of a key insulin-regulated gene promoter to investigate hepatic IR and its role in development of T2DM. This peptide is secreted into the blood and urine, and is quantified by ELISA. Therefore peptide levels will be directly related to promoter activity and hence be a surrogate of IR. Peptide measurements will be compared with current methods of assessing IR, including gold standard hormone clamp studies. The novel mouse will be made available, for crossing with models of diabetes, providing a non-invasive, accurate technique for the assessment of IR in vivo. These tools will improve research into the development of IR and T2DM.
The parasitic diseases, Leishmaniasis, African sleeping sickness and Chagas' disease, annually cause over 120,000 deaths world-wide. Despite this terrible death toll, the available drugs are generally not fit for purpose, suffering from multiple issues, such as lack of efficacy and unacceptable levels of toxicity, including death. Despite encouraging developments, significant gaps are still impeding the discovery of new treatments for these diseases. These include a general lack of validated targets, drug discovery effort, and insufficient hits and leads to counteract the normal attrition of drug discovery. We will address these gaps through a unique alliance between the university based Drug Discovery Unit and the major pharmaceutical company Pfizer. The consortium brings together Dundee's world renowned parasitology and extensive experience developing hits and leads for neglected diseases, and Pfizer's substantial later stage discovery and development expertise and infrastructure. Pfizer's extensive target-based knowledge and chemical matter will substantially strengthen our ability to sustain a portfolio of antiparasitic projects, through to the delivery of clinical development candidates with our established partner, DNDi. Science 10 Our goal is to deliver at least one credible pre-clinical candidate, together with a pipeline of hits and leads for one or more of these diseases within the 5 year programme.
Factors modulating the effects of filaggrin haploinsufficiency in ichthyosis vulgaris and atopic eczema. 04 Dec 2008
Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and are significantly associated with atopic eczema. FLG null mutations are prevalent in the European population, with a combined allele frequency of 0.09. However, the penetrance has been estimated at between 42% and 79% in atopic eczema, demonstrating the importance of factors modulating the effects of filaggrin haploinsufficiency in skin disease. This project aims to test three hypotheses: (1) Copy number variation bot h within and around the FLG locus modulates penetrance. Assays to detect copy number variants will be developed and applied to the study of established cohorts of children with eczema. (2) FLG expression demonstrates positive and negative interactions with other genes involved in epidermal barrier function. This will be investigated using microarray technology and findings corroborated with quantitative PCR and immunoblotting. (3) FLG null mutations result in a reduced amount of epi dermal histidine, which affects response to UVB therapy. The response of eczema patients to phototherapy will be correlated with FLG null status in a retrospective pilot study, followed by a more detailed prospective study. The proposed research will improve understanding of the mechanisms by which FLG null mutations and filaggrin deficiency contribute to the pathogenesis of eczema.
The overall aim of this project is to characterise the interactions of Tat substrates with signal peptide binding chaperones and with the TatBC receptor complex, with the intent of using the findings to guide development of assays that can be used in high throughput screening of small drug-like molecules targeting TatBC signal peptide binding. The project will be split into three specific objectives: I. Structural characterisation of the Tat substrate Tor A in complex with its signal peptide binding chaperone TorD using the E. coli and homologous Salmonella protein pairs and using modem structural biology techniques. 2. Investigation of how substrates are handed over to the TatBC complex and development of in vivo and in vitro assays to measure this. 3. Development of an in vitro assay to assess substrate interaction with the TatBC complex that will be used to screen for small molecule inhibitors.
Comparative transcriptomics of blood stream and procyclic form of Trypanosoma brucei and investigation of its mRNA methyl cap structure and function 14 Jun 2010
In Human African trypanosomiasis (HAT), the causative parasite Trypanosoma brucei (T. brucei) undergoes a transition between the Tsetse fly vector (procyclic form) and mammalian host (blood stream form) (1). A better understanding of the disease transmission cycle is imperative for the development of new therapeutic targets because substantial changes in protein expression occur when the parasite transitions from one stage to the next. This proposed project's overarching question asks is the T. brucei proteome substantially controlled at the level of mRNA selection by ribosomes; and if so, what is the mechanism of this selection. Aim 1: Perform RNAseq (in collaboration with the Wellcome Trust Sanger Institute) of total polA+ and polyribosomal RNA purified from blood stream form (bsf) and procyclic form (pcf) T. brucei followed by bioinformatic analysis comparing the transcript profiles. Aim 2: Correlate transcriptome data with proteomic analysis, using the SILAC method, of global protein expression levels in bsf and pcf T. brucei. mRNA processing in eukaryotic cells involves the addition of the 7-methylguanosine cap (methyl cap) to the first nucleotide of the 5' end of the transcript. Since the methyl cap is essential for gene expression in all eukaryotes investigated we will investigate whether it is essential in trypanosomses and whether the enzymes that catalyze formation of the methyl cap are potential drug targets. In the vast majority of eukaryotes methyl cap formation is catalysed by a single guanylyltransferase and a single methyltransferase. Trypanosomes are highly unusual in that they have an additional guanylyltransferase and methyltransferase on a single polypeptide (2). Aim 3: Our approach is to knock out the single methyltransferase and the bifunctional methyltransfere/guanylyltransferase and determine the effect on cell viability. If either enzyme is required for cell viability, it will be pursued further as a drug target with the drug discovery unit. The effect of methyltransferase knock-out on transcript stability, splicing, and translation will also be investigated to determine the effect of the methyl cap in trypanosomes.
Functional and molecular characterisation of human keratin 9 to further develop RNAi-based therapeutics for EPPK 14 Jun 2010
The primary aim of this research project is to gain a better understanding of the functional importance and molecular activities of KRT9 in the palmoplantar epidermis so that we may further develop our potential RNAi-based therapeutics for Epidermolytic Palmoplantar Keratoderma (EPPK) into clinically applicable treatments. To this end, we aim to: 1. Define the functional importance of KRT9 in the palmoplantar epidermis via generation and characterization of KRT9 knockout mice. 2. Establish an in vitro PPK culturing system for evaluating novel therapeutics and characterizing the molecular activities of KRT9. 3. Explore and develop in vivo siRNA delivery methodologies for therapeutic treatment of EPPK.
Signalling mechanisms regulating differentiation progression in mouse embryonic stem cells and embryos. 15 Feb 2010
The proposed experiments investigate signalling mechanisms that promote differentiation progression of pluripotent cells and analogous cell populations in the developing mouse embryo Specifically, we plan to address the involvement of retinoid signalling in the acquisition of somatic cell fates in these contexts. We will: i) define early epiblast-like cell populations cultured in vitro with respect to the developing embryonic epiblast; ii) determine the role and requirement for retinoid signalling for differentiation of Epistem cells and mouse embryonic epiblast; iii) employ a genome-wide microarray screen to identify mediators of RA or FGFR inhibition-driver differentiation of Epistem/day1 ES cells and validate and functionally test a key subset of FGFR regulated genes in these cells and in the embryo.
The interplay between the Notch and Wnt signalling pathways in somitogenesis This project aims to investigate the potential crosstalk between the Notch and Wnt signalling pathways in the important process of somitogenesis. It is well established now that the Notch pathway plays a crucial role in somitogenesis during vertebrate embryogenesis in a variety of species. More recently it was shown that the Wnt pathway is also required for this process in the mouse embryo. It was also reported that Wnt may play a role upstream of Notch in this process. The first aim of the project is to confirm and extend preliminary findings that Notch may be upstream of Wnt in chick somitogenesis. The second aim of the project is to examine the level of interplay between the two pathways in both the mouse and the chick embryo. Establishing how the Notch and Wnt pathways control somitogenesis will be an important step in understanding how this process is regulated.
Wellcome Trust PhD Programme for Clinicians at the University of Dundee: Defining the role of the LKB1-AMPK signalling pathway in cancer and DNA damage. 13 Apr 2010
AMP-activated protein kinase (AMPK) detects changes in AMP: ATP ratio and functions as an energy sensor in cells. Activation of AMPK leads to activation of catabolic processes and inhibition of anabolic processes. In addition to its metabolic effects, AMPK also causes a G1 phase cell cycle arrest. LKB1, a tumour suppressor, is the main upstream kinase that activates AMPK. AMPK also has several downstream targets such as TSC2 and Raptor (mTOR complex) that are implicated in tumourigenesis. Recent evidence suggests that many tumour cells may have down-regulated AMPK signalling. For example, some tumour cells have lost LKB1 expression. The aims of the PhD are to look at the mechanisms underlying loss of AMPK signalling in tumour cells. We will particularly examine the role of the C- terminal tail of LKB1 and the effect of its phosphorylation on AMPK activation. It has been reported that ionising radiation induces ataxia- telangectasia mutated (ATM) kinasemediated phosphorylation of LKB1 at Thr-366. We will look at the effect of this phosphorylation on AMPK activation, which may explain in part how ionising radiation affects cell fate. We will also study the role of DNA damaging chemotherapeutic agents (such as cisplatin and etoposide) on this pathway. We will also develop a mouse model, knocking out AMPK in T lymphocytes which lack one PTEN allele to see if loss of AMPK accelerates development of lymphomas.
The thiazide-sensitive Na+:Cl- cotransporter (NCC) is the main pathway for salt reabsorption in the distal convoluted tubule in mammalian kidney. Work recently done by others have shown that angiotensin II, the pro-hypertensive hormone, increases the trafficking of NCC to the apical membrane, and thus activity, and we have recently proposed a molecular mechanism for such regulation. We have demonstrated in Xenopus oocytes that upon angiotensin II signal, WNK4 turns from an inhibitor to an activa tor of NCC and that this effect depends on WNK4 activating effect on another serine/threonine kinase known as SPAK. Thus, WNK4 behaves as a molecular switcher that changes the kidney from a salt-losing to a salt retaining state. This is a very important molecular mechanism increasing our understanding of blood pressures regulation. However, because our observations were done using an in vitro model, the proposed mechanism required to be confirmed, analyzed, and characterized in vivo. In this s tudy we plan to use three different genetically altered mice in which the expression of WNK4 or SPAK has been altered to analyze the effect of a physiological condition (low salt diet, a high angiotensin state) and of a pathophysiological condition (arterial hypertension induced by angiotensin II administration).
An investigation into the synergistic impact of sublethal exposure to industrial chemicals on the learning capacity and performance of bees 25 May 2010
Many industrial and household pesticides act on the insect nervous system. However, significant 'off-target' toxicity can also occur in beneficial insects, including bees. The major classes of nervous system insecticide used in the UK act on synaptic transmission. They include potentiation of voltage-gated sodium channels (pyrethroids), inhibition of acetylcholinesterase (organophosphates & carbamates), activation of nicotinic acetylcholine receptors (neonicotinoids) or blocking inhibitory receptor function (thymol, fipronil, avermectins). If present in combination, such agents have potential for additive or synergistic effects. Similarly, fungicides and herbicides have been reported to exhibit unexplained synergy with insecticides. Our multi-disciplinary study will investigate the potential synergistic interactions of industrial agents on bee health using a diverse range of experimental approaches. At the molecular level, quantitative fluorescence assays will use medium throughput screening of cultured bee brain neurons to investigate interactions at the cellular level. These studies will be complemented by brain slice electrophysiology to investigate interactions at the neural network level and the consequences for synaptic plasticity. Results from these screening techniques will feed into behavioural tests of individuals and colonies using a range of learning paradigms in both honeybees and bumblebees. Potential effects of pesticide exposure on bee locomotion, foraging ability and navigation will be determined in laboratory and field experiments. Information generated by the coordinated efforts of all 5 laboratories will be augmented by a survey of experienced amateur beekeepers. Results from this programme will contribute significantly to the development of a coordinated strategy on pesticide use to minimise harmful effects to bees. Finally, we aim to develop several bee cell lines that are desperately needed for the rapid screening of future pesticides.
Our recent work has demonstrated that common loss of function variants in the filaggrin gene are the major predisposing factor in atopic eczema and related allergic diseases. Here, our overarching research goal is to extend this work to determine the role the filaggrin family of proteins in atopic disease, using human and mouse genetics, to uncover further atopy genes. Specifically, we will analyse the filaggrin gene in a number of human ancestral groups to identify ethno-specific mutatio ns linked to atopic disease. We will identify further atopy susceptibility genes in the filaggrin gene cluster using high-density SNP genotyping, copy number analysis and sequencing strategies. We will determine the genetic defect in the matted mouse mutant, which maps to the murine filaggrin gene cluster and which has an atopic phenotype. This will inform and direct our human genetics studies. We have shown that the atopic phenotype in filaggrin deficient mice is highly strain depen dent. We will use this unique resource to identify modifier loci and mouse and relate these to human disease by backcross mapping and eQTL analysis.