DPFS Devolved Portfolio (Pilot)
Lead Research Organisation:
Cardiff University
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
This is an award of a devolved portfolio under a pilot phase, as part of the implementation of the Development Pathway Funding Scheme (DPFS). DPFS Devolved Portfolios are block awards for specific universities to support goal-orientated translational research projects. The award allows universities to allocate the money to different translational projects more responsively based on their relative progress. For example the university might decide to stop a particular project and recycle the money allocated to it into other proposals. All projects supported by the Portfolio fall within the remit of the Development Pathway Funding Scheme (DPFS).
Organisations
- Cardiff University (Collaboration, Lead Research Organisation)
- University of Manchester (Collaboration)
- University of Sheffield (Collaboration)
- Southmead Hospital (Collaboration)
- MRC-Technology (Collaboration)
- Johnson & Johnson (Collaboration)
- MBi (Wales) Ltd (Collaboration)
- KWS Biotest (Collaboration)
People |
ORCID iD |
Publications
Adams S
(2012)
Potent inhibition of Ca 2+ -dependent activation of calpain-1 by novel mercaptoacrylates
in Med. Chem. Commun.
Azzopardi EA
(2013)
Colistin in burn intensive care: back to the future?
in Burns : journal of the International Society for Burn Injuries
Azzopardi EA
(2013)
Colistin past and future: a bibliographic analysis.
in Journal of critical care
Azzopardi EA
(2013)
The enhanced permeability retention effect: a new paradigm for drug targeting in infection.
in The Journal of antimicrobial chemotherapy
Cates MJ
(2012)
Neurogenic hypertension and elevated vertebrobasilar arterial resistance: is there a causative link?
in Current hypertension reports
Coulthard EJ
(2012)
Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.
in Brain : a journal of neurology
Dewitt S
(2013)
Ca²? and calpain control membrane expansion during the rapid cell spreading of neutrophils.
in Journal of cell science
Forsyth LH
(2012)
In Vitro and In Vivo Recording of Local Field Potential Oscillations in Mouse Hippocampus.
in Current protocols in mouse biology
Francis RJ
(2013)
Ca2+ activation of cytosolic calpain induces the transition from apoptosis to necrosis in neutrophils with externalized phosphatidylserine.
in Journal of leukocyte biology
| Description | Development of a University Research Institute for Health |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Description | A4B |
| Amount | £140,473 (GBP) |
| Organisation | Health and Care Research Wales |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | BBSRC Spark with Impact award |
| Amount | £18,088 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2013 |
| End | 11/2014 |
| Description | BHF Programme Grant |
| Amount | £980,500 (GBP) |
| Funding ID | RG/12/6/29670 |
| Organisation | British Heart Foundation (BHF) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2013 |
| End | 02/2018 |
| Description | BRACE Charity funding |
| Amount | £21,000 (GBP) |
| Organisation | BRACE (Alzheimer's disease charity) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | Chairman's Award |
| Amount | £25,000 (GBP) |
| Organisation | Cardiff and Vale University Health Board |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | DPFS Devolved Portfolio |
| Amount | £2,000,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | DPFS Resources- A Core Protein Production Facility |
| Amount | £429,787 (GBP) |
| Funding ID | G0801676 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | EPSRC Directed Assembly Network 2 |
| Amount | £2,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2013 |
| End | 04/2014 |
| Description | EPSRC Directed assembly network grant |
| Amount | £2,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2013 |
| End | 07/2014 |
| Description | EPSRC Doctoral Prize Fellowship |
| Amount | £50,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2013 |
| End | 06/2014 |
| Description | EPSRC Project Grant |
| Amount | £455,618 (GBP) |
| Funding ID | EP/J015318/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2012 |
| End | 09/2015 |
| Description | European Social Fund |
| Amount | £70,000 (GBP) |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | MRC Astra-Zeneca |
| Amount | £635,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2013 |
| End | 03/2017 |
| Description | MRC Research Grant |
| Amount | £1,000,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | MRC Senior Non-Clinical Fellowship |
| Amount | £2,000,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | NISCHR PhD Studentship |
| Amount | £53,928 (GBP) |
| Organisation | Health and Care Research Wales |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | Ser Cymru National Research Network PhD studentship |
| Amount | £40,000 (GBP) |
| Organisation | Government of Wales |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2013 |
| End | 10/2016 |
| Description | The Dunhill Medical Trust |
| Amount | £109,401 (GBP) |
| Organisation | The Dunhill Medical Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | Translational Imaging Post - Senior Lectureship |
| Amount | £138,516 (GBP) |
| Organisation | Health and Care Research Wales |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2009 |
| End | 12/2011 |
| Description | Wales Clinical Academic Track Fellowship |
| Amount | £500,000 (GBP) |
| Organisation | Health and Care Research Wales |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | Wellcome Trust ISSF |
| Amount | £49,838 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2012 |
| End | 10/2013 |
| Description | Wellcome Trust Strategic Award |
| Amount | £5,000,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | Wellcome Trust Value in People Award |
| Amount | £41,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Title | Azide containing GFP variants |
| Description | Several new variants of GFP - Green fluorescent protein containing azide groups which can be modified by light. Light induced modification by photolysis has been demonstrated including in cells for confocal imaging. These have great potential for high resolution imaging and wider implication in terms of optpgenetics. |
| Type Of Material | Technology assay or reagent |
| Provided To Others? | No |
| Impact | TBC |
| Title | Compound generation database |
| Description | Custom Access database to log compound generations and associated data to progress development |
| Type Of Material | Technology assay or reagent |
| Provided To Others? | No |
| Impact | none yet known |
| Title | Human Trk cell lines |
| Description | Cell lines: mammalian cell lines with relevant receptors expressed stably: hTrkA, rodent TrkA, hTrkB, hTrkC, hp75. |
| Type Of Material | Cell line |
| Year Produced | 2011 |
| Provided To Others? | Yes |
| Impact | Material is required for SAR assays and other aspects of programme |
| Title | Labelled Calpain inhibitor |
| Description | Fluorscently labelled calpain inhibitor for use in competitive binding assay |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2012 |
| Provided To Others? | Yes |
| Impact | synthesised in Nov 2011 so none as yet. |
| Title | System for screening in-frame TAG mutations |
| Description | System for screening in-frame TAG mutations (introduction of the amber stop codon for orthogonal incorportaion of non-natural amino-acids) using a GFP (green fluorescent protein) based approach. |
| Type Of Material | Technology assay or reagent |
| Provided To Others? | No |
| Impact | None as yet |
| Title | mouse model of SSRTT |
| Description | Unique methodology of combined electrophysiology and mouse SSRTT |
| Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
| Year Produced | 2011 |
| Provided To Others? | Yes |
| Impact | Joint funding from MRC project grant in order to collaborate |
| Description | Boswellia Sheffield University |
| Organisation | University of Sheffield |
| Department | Department of Neuroscience |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Extracts of Boswellia have been provided for testing |
| Collaborator Contribution | Dr Andy Grierson is testing the Boswellia extract in an in vivo model of motor neurone disease |
| Impact | TBC |
| Start Year | 2011 |
| Description | Boswellia, Dental School |
| Organisation | Cardiff University |
| Department | School of Dentistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Boswellia extracts supplied for testing |
| Collaborator Contribution | Boswellia extracts are being tested in an invivo model of peridontal disease |
| Impact | TBC |
| Start Year | 2011 |
| Description | Bristol Urological Institute |
| Organisation | Southmead Hospital |
| Department | Bristol Urological Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have devloped the sensors which are now entering alinical trials at BUI |
| Collaborator Contribution | BUI are carrying out a clinical trial with the Catheter Encrustation sensors |
| Impact | MHRA approval for the trial |
| Start Year | 2011 |
| Description | Cardiff and Bristol Neuroscience |
| Organisation | Cardiff University |
| Department | School of Psychology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Connecting a confirmed schizophrenia risk gene to neuronal, network and behavioural function |
| Collaborator Contribution | joint knowledge in methodology and techniques |
| Impact | None yet |
| Start Year | 2011 |
| Description | Honorary Research Fellow visiting from pharmaceutical industry |
| Organisation | Johnson & Johnson |
| Country | United States |
| Sector | Private |
| PI Contribution | The Visiting Fellow will advise SARTRE and associated academics on potential partnerships and collaborations |
| Collaborator Contribution | Has strengthened the links between academia and industry |
| Impact | Recent collaboration |
| Start Year | 2010 |
| Description | Janssen Pharmaceutica |
| Organisation | Johnson & Johnson |
| Department | Janssen-Cilag |
| Country | Global |
| Sector | Private |
| PI Contribution | Academic expertise using unique methodology. |
| Collaborator Contribution | The collaboration will bring together the use of technology owned by the company with expertise from the academic research team. In addition to the money, a joint PhD studentship was awarded to work on both sites. |
| Impact | No outcome yet |
| Start Year | 2011 |
| Description | KWS Biotest |
| Organisation | KWS Biotest |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Boswellia extracts supplied for testing |
| Collaborator Contribution | Boswellia extracts will be tested in an invivo model of colitis. |
| Impact | TBC |
| Start Year | 2011 |
| Description | MBI Wales |
| Organisation | MBI (Wales) Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Have developed the sensor in collaboration. We have also contributed the microbiological expertise and in vitro testing. |
| Collaborator Contribution | MBI have contributed to the development of the sensor, the development of the silicone based sensor, machining and production of sensors for testing. MBI Wales are also producing and supplying the sensors free of cost for clinical trials. |
| Impact | MBI Wales have a Formal option agreement with Cardiff University to License and manufacture the sensor following clinical trials. This is a multidisciplinary collaboration involving microbiology, engineering and materials science. |
| Description | MRC-T TrkA Programme |
| Organisation | MRC-Technology |
| Department | MRCT Centre for Therapeutics Discovery (CTD) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Advice on target of interest (TrkA) and discussions around go/no go decisions; joint project management. |
| Collaborator Contribution | Collaboration will add value to the devolved portfolio funding project by running HTS, assays and medicinial chemistry guidance thus strengthening the capabilities of the funded research team. |
| Impact | No outcomes yet. |
| Start Year | 2011 |
| Description | VanSel Study CRT |
| Organisation | University of Manchester |
| Department | Cancer Research UK Manchester Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Our contribution to this Phase I trial will be to analyse the expression and phosphorylation of tumour biopsy samples provided using the CB1000 machine that was funded with the devolved portfolio award. |
| Impact | This multicentre clinical trial is being set up by CRT and will commence in early 2012. |
| Start Year | 2011 |
| Title | INHIBITOR OF INFLAMMATORY CONDITIONS |
| Description | The invention relates to Boswellia frereana and particularly an extract of same for treating a range of inflammatory disorder or conditions selected from the group comprising: articular cartilage degradation or arthritides, osteoarthritis, rheumatoid arthritis, inflammatory bowel disease (IBD), all forms of muscular dystrophy especially Duchenne muscular dystrophy, sepsis, sepsis syndrome, osteoporosis, ischemic injury, graft vs. host disease, reperfusion injury, asthma, diabetes, cancer, myelogenous and other leukemias, psoriasis and cachexia, Alzheimer's Disease, demyelinating neurological disorders including multiple sclerosis, Acetylcholinesterase mediated disorders, retinal disorders, neurological, retinal, and muscular disorders. |
| IP Reference | WO2011010080 |
| Protection | Patent application published |
| Year Protection Granted | 2011 |
| Licensed | Commercial In Confidence |
| Impact | Commercial discussion are in progress with a number of commercial organisations and the material has been supplied to collaborators for in vivo tests (See Collaborations and Partnership) |
| Title | THERAPEUTIC CONJUGATES |
| Description | The invention concerns a novel anti-microbial peptide (AMP) polymer conjugate comprising at least one AMP, typically colistin, and a dextrin polymer wherein said dextrin polymer has a molecular weight between 5,000-60,000 g/mol and is modified by the additions of pendant groups which increase the stability of the conjugate and so delays its degradation thereby slowing the rate at which the AMP is released. |
| IP Reference | WO2012035310 |
| Protection | Patent granted |
| Year Protection Granted | 2012 |
| Licensed | No |
| Impact | Has provided the basis for applications for funding to progress to clinical studies |
| Title | Antiviral agents for the treatment of human cytomegalovirus and poxvirus infections |
| Description | "We have discovered bicyclic pyrimidine nucleoside analogues (BCNAs): a new family of antiviral agents, with potent and selective action against Varicella Zoster Virus (VZV). BCNAs, designed and developed in Cardiff have entered clinical trial for shingles. Structural modification to generate dideoxy BCNA (ddBCNA) analogues leads to a loss of anti-VZV activity but the surprising introduction of selective activity against human cytomegalovirus (HCMV). The early lead compounds cf1821 and cf2095 are equi-active with the established HCMV drug ganciclovir. We have found novel L-enantiomers of these agents (cf2642) have enhanced antiviral activity against vaccinia virus, showing a potential for treatment of (small)poxvirus infections. These compounds appear to act via a novel mechanism, at viral entry, and share no cross-resistance with current agents. Given the unmet medical need of HCMV, the bioterror interests in (small)pox, and novelty of new compounds they represent new and promising leads for drug discovery. We will use our virology expertise to further optimize the lead compounds for antiviral activity, taking advantage of their UV fluorescence to track their cell entry. Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | On hold |
| Impact | TBC |
| Title | Bioresponsive polymer-peptide conjugates as novel antibacterial agents |
| Description | "This project will develop IP based on our discovery of a new method of drug delivery for the safe administration of antibiotics, currently rendered unusable due to toxicity issues. This programme will generate a library of antibiotic conjugates engineered for use in distinct human disease processes where Gram-negative antimicrobial resistance represents a major clinical challenge (cystic fibrosis and skin wounds). The conjugates will be optimised in a series of in vitro studies (including physicochemical characterisation and microbiological assays). The delivery system offers the opportunity to effectively target the antibiotic, which, following systemic administration, selectively accumulates at sites of inflammation and infection. This phenomenon effectively reduces the toxicity and increases the bioavailability of the antibacterial peptide. Seedcorn funding will develop and characterise these antibiotic conjugates to enhance the IP potential of the research prior to clinical testing and full-scale commercial development. Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | The patent covering this work has been enhanced by this activity and will be published and the end of Dec 2011. Protocols for in vivo studies for efficacy and safety have been prepared and studies are due to start Dec 2011. |
| Title | Calpain-1 small molecule inhibitors for anti-inflammatory therapy |
| Description | "With a greater understanding of the processes involved in inflammatory disease, ""biologics"" such as anti-cytokine antibody can be a useful therapy. There are problems however, including their high cost: the need for intravenous infusions: and the high specificity of the antibody which limits their usefulness to diseases in which the targeted cytokine is the ""driver"" or rate limiting step. Our approach however aims (i) to inhibit a rate limiting step common to inflammatory cell extravasation (regardless of the cytokines ""drivers"") by (ii) producing a small molecule inhibitor which can be taken orally. Our approach aims to inhibit the enzyme underlying the white cell morphology change ("spreading" onto the endothelium), namely the intracellular enzyme calpain-1, From knowledge of the structure of the novel Ca2+ binding site on calpain-1, blocking molecules are being designed. We are therefore synthesising compounds which target activation of this enzyme. We already have a novel calpain-1 inhibitor at least 10 times more potent that others reported to date. Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2013 |
| Development Status | Actively seeking support |
| Impact | TBC |
| Title | Detection of impending catheter blockage |
| Description | We have developed a biosensor that in an in vitro bladder model consistently predicts catheter blockage, 24 h before it occurs. Whilst the sensor successfully indicates impending blockage, its performance can be enhanced by modification of its surface topography. The aim of this study is to generate a range of biosensors of different surface roughness and compare their relative performance to predict catheter encrustation. Optimal sensors will then be produced by injection moulding methods and confirmed to retain their high performance. Most recent work supported by DPFS Portfolio Award Now in Clinical trials supported by the Chairman's Award from Cardiff and Vale NHS and the Bristol Urological Institute |
| Type | Therapeutic Intervention - Medical Devices |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | TBC |
| Title | Development and validation of translational approaches to facilitate neurobiological and therapeutic advances in anxiety research. |
| Description | "This project utilises a reverse translation approach to develop and validate a novel approach to anxiety research. I have extensive experience of working in research groups that cross clinical and pre-clinical studies into psychiatric disorders. My PhD and subsequent research were undertaken in the Psychopharmacology Unit, Bristol with Prof Nutt and my fellowship enabled me to work the Cambridge Behavioural and Clinical Neuroscience Institute in Experimental Psychology in Cambridge. Using this background I have been able to develop a model that has the potential to detect a core symptom of anxiety disorders, negative affective state. Having used reverse translation to develop this approach, we now propose to take this model back into humans thus enabling us to take this strategy from bedside to bench and back again. This project will combine our model development with a second, translational method, the use of CO2- inhalation to induce anxiety. Most recent work supported by DPFS Portfolio Award" |
| Type | Support Tool - For Medical Intervention |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | TBC |
| Title | Diagnostic Probe Array Sensors for Sepsis and Blood Screening |
| Description | "The project will allow mechanical sensor techniques to be developed for the clinical environment as a practical improvement on conventional ELISA tests. It will give clinicians easy and immediate access to information about possible sepsis and its severity in patients allowing immediate response, dramatically increasing the prognosis. The project is based on the integration of new developments in mechanical sensor production and detection, where several of our own innovations in nanosensor instrumentation combined with recent research will facilitate optimization of the nanosensors for applications in liquids to the level necessary that even detection of prion infection in blood samples seems to be achievable. The goal of the project is to develop a proof-of-concept device that can be taken to a product that provides a new rapid diagnostic tool at the point of care. Most recent work supported by DPFS Portfolio Award" |
| Type | Diagnostic Tool - Non-Imaging |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | TBC |
| Title | Enhanced protein therapuetics by optimisation of site specific post-translational derivatisation. |
| Description | "Protein therapeutics are a lucrative product stream for the pharmaceutical industry. To tackle some of their inherant problems (e.g. poor stability, short shelf-life, antigenic side-effects and poor pharmacokinetics), protein therapuetics are routinely derivatised posttranslationally with chemical entities such a polyethylene glycol (PEG). The drawback of PEGylation is that its effects on protein function are unpredictable. The problem is exacerbated by the fact that introduction of the PEG molecule on the protein is typically performed at a protein terminus or randomly on the protein surface. To address these issues, a novel proprietary protein mutagenesis tool will be used together with an expanded genetic code to incorporate unnatural amino acids into proteins at defined positions during cellular protein synthesis. The new chemistry inherent in the unnatural amino acid will allow protein modification by PEG at a specific position in a defined way so that both stability and bioactivity are maximised. Novel variants of Keratinocyte Growth Factor have been developed. Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Actively seeking support |
| Impact | TBC |
| Title | Human hypertension and cerebral artery stenosis |
| Description | "In human cadavers a correlation exists between vertebral artery diameter and hypertension: narrower arteries-higher blood pressure. The question raised is whether the hypertension caused this narrowing or whether the narrowing (and reduced blood flow) caused the hypertension. In a hypertensive animal model, this re-modelling was also found but, interestingly, occurred before the hypertension. This supports our hypothesis that stenosed vertebral arteries, and subsequent poor perfusion of the brainstem, is a cause for hypertension. We wish to: (i) confirm the observations in living hypertensive man that there is a narrowing of cerebral vessels using magnetic resonance angiography (MRA) and, (ii) assess the prevalence of this condition and (iii) establish whether antihypertensive medication reverses cerebral artery stenosis. This study may have prognostic value and provide improved treatment regimes for hypertension, which is an escalating health issue since the numbers of those becoming resistant to drug treatment is ~25%. Most recent work supported by DPFS Portfolio Award" |
| Type | Diagnostic Tool - Imaging |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | TBC |
| Title | New agents for colorectal cancer (CRC) using genetically defined autochthonous models |
| Description | This proposal seeks funding to develop in house leads against metastatic colorectal cancer (MCRC), using modern medicinal chemistry, molecular modelling, and genetically defined invasive tumours arising autocthanously in transgenic mice. Using our established ProTide platform for the intracellular delivery of bioactive nucleotides, a 2nd generation family of agents related to the 1st generation MCRC drug thymectacin has been prepared. The funding will support the use of medicinal chemistry methods to develop these hits towards leads, aided by extensive local support and expertise particularly in the provision of appropriate transgenic mice and other sophisticated in vivo models of clinical relevance. Molecular modelling methodologies such as docking and 3D-QSAR, and exploiting the local high performance computing and visualisation facility will aid rational candidate selection. We will use our established in house high field multi-nuclear NMR-based screens for plasma stability, acid stability (for oral dosing), and metabolism in target and non-target tissue as potential predictors of in vivo exposure and efficacy/potency. The successful transitioning of leads tto early development will be established through potential license deals and/or research collaboration with leading commercial partners in the field, following business models that have been successful in these laboratories. 70 New chemical entities (protides) have been sythesised and tested to select lead compounds for animal testing Most recent work supported by DPFS Portfolio Award |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | TBC |
| Title | Quantitative analysis of EGFR signalling in lung cancer: improving prediction of tumour response and patient survival |
| Description | "Predicting tumour response and survival benefit to chemotherapy in individual patients is an increasingly important aspect of cancer therapy. This is particularly the case for the orally available EGF receptor tyrosine kinase inhibitors erlotinib/Tarceva and gefitinib/Iressa in the treatment of non-small cell lung cancers. This proposal will build on our observation that only a fraction of EGFR-positive tumours exhibit elevated EGFR signalling activity, and our prediction that only these patients will respond to inhibitor therapy. In this proposal we plan to adapt and optimise the tissue collection and protein detection methodology (focussing on a new, quantitative and exquisitely sensitive technology) such that we can measure EGFR signalling activity in samples obtained during routine clinical diagnosis. The methodology will then be used in a feasibility study of EGFR signalling in patients enrolled in an erlotinib trial. This will provide the data necessary to secure substantial follow-on funding to undertake a fully powered multicentre prospective clinical trial aimed at testing our central hypothesis, and so deliver a validated companion diagnostic for routine clinical practice. This has the potential to improve patient care and clinical outcomes, and also to allow significant cost savings to the NHS and other health care providers. Most recent work supported by DPFS Portfolio Award" |
| Type | Diagnostic Tool - Non-Imaging |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | TBC |
| Title | Small molecule antagonists at the TrkA receptor for the treament of pain |
| Description | "Nerve growth factor (NGF) is a key mediator in neuropathic and inflammatory pain. We have shown that sequestration of NGF abrogates pain in many conditions. Antagonism of the NGF/TrkA (tyrosine kinase receptor A) interaction will have similar benefits, and we have identified and validated the NGF binding domain of TrkA (TrkAIg2) as a target. We identified different classes of TrkA antagonists in silico; which have been confirmed in vitro. One compound was used for the rational design and synthesis of a series of low molecular weight, high affinity compounds. We have identified residues on the isolated TrkAIg2 which interact with compounds tested using protein nuclear magnetic resonance (NMR) analysis. Our established interdisciplinary team has expertise in biochemistry, NMR, molecular modelling, synthetic chemistry and in vivo validation. We plan to develop these compounds further towards entry into clinical trials as moderators of intractable pain states such as osteoarthritis and post-operative pain Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Actively seeking support |
| Impact | TBC |
| Title | Testing the efficacy of Boswellia frereana (Frankincence) as a nutraceutical for Osteoarthritis. |
| Description | "Articular cartilage degradation is a classical feature of degenerative and inflammatory arthritides. The incidence of osteoarthritis (OA) is more prevalent in our ageing and increasingly obese population (1); current therapeutic strategies provide some pain relief, but adverse side effects make these less than desirable for chronic conditions. Identifying other potential pharmaceutical agents which can alleviate the symptoms associated with OA, whilst remaining efficacious and non-toxic, is an ongoing pursuit. Previously, we have demonstrated that treatment of cytokine-stimulated cartilage explants with Boswellia frereana - a novel Frankincence species, inhibited breakdown of the collagenous matrix, reduced MMP levels and significantly reduced nitric oxide, prostaglandin E2 and cycloxygenase-2 production. Epi-lupeol was identified as the principal constituent of B. frereana. We have now optimised the dose of B. frereana required to inhibit cytokine-induced degradation and determined that the active constituent is epi-lupeol. Most recent work supported by DPFS Portfolio Award" |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | The Bowellia frereana extract have now been supplied to several partners for in vivo testing. See Collaboration and Partnership |
| Title | The neurophysiological basis of response inhibition and its use in diagnosis of complex frontal cortical dysfunction |
| Description | "Dysfunction of frontal cortices and their interactions with connected brain regions underpins overlapping cognitive impairments in an array of disorders including schizophrenia, ADHD, autism, Parkinson's disease, fronto-temporal dementia and Alzheimer's Disease. However, the extent to which similar behavioural abnormalities arise from common neural causes across this range of disorders remains unknown, limiting the scope for precise diagnoses and subsequent targeted treatments. As an entry point to this fundamental problem we will focus on response inhibition, a core component of frontal functioning, and combine behavioural testing in the Stop Signal Reaction Time Task with electrophysiological recordings in both human and mouse models with the aim of establishing sensitive and selective translational measures of frontal cortical function and dysfunction. These informative biomarkers have the potential to make an important contribution to accurate and consistent diagnoses and development of therapies targeted according to defined individual cognitive phenotypes in patients. Most recent work supported by DPFS Portfolio Award" |
| Type | Support Tool - For Medical Intervention |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | Under active development/distribution |
| Impact | TBC |
| Title | Tool for the assessment of impulsivity |
| Description | "Over-impulsive behaviour is a feature of many neurological and psychiatric disorders, e.g., patients treated with dopamine agonists (20%) or deep brain stimulation for Parkinson's, Tourette's, mania, obsessive compulsive disorder, autism, schizophrenia and Huntington's disease. Such over-impulsivity results in serious consequences for patients including pathological gambling and even suicide. Seemingly similar impulsive behaviour across patients may be caused by diverse neuropathology, requiring different treatments. Currently clinicians rely on questionnaires and clinical interview to identify impulsivity and the neurobiological basis of the behaviour is not addressed. For development of targeted treatment, one must first have a tool that both accurately characterises the cognitive subsystem damaged and quantifies the degree of impairment. Currently no such objective test exists. We plan to develop a computerised cognitive task as a tool for measuring and characterising impulsivity in patients. Such a tool could be applied to treatment trials and during clinical assessment. Most recent work supported by DPFS Portfolio Award" |
| Type | Support Tool - For Medical Intervention |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2011 |
| Development Status | On hold |
| Impact | TBC |
| Description | BioWales 2010 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Health professionals |
| Results and Impact | Regional forum for biotech in Wales. Presented SARTRE and novel collaboration models with private sector Follow-up discussions |
| Year(s) Of Engagement Activity | 2010 |
| Description | MRC Fellows Symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Type Of Presentation | Keynote/Invited Speaker |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Presentation at Annual MRC Fellows' Symposium Peer discussion |
| Year(s) Of Engagement Activity | 2012 |
| Description | Mediwales University Challenge Event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Presentation on translational research in Universities to audience mostly from local industry and Welsh government. Engagement with local industry |
| Year(s) Of Engagement Activity | 2011 |
| Description | One Nucleus |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Health professionals |
| Results and Impact | Presentation in London to promote novel collaborative models between industry, academia and health providers. Follow-up discussions |
| Year(s) Of Engagement Activity | 2010 |
| Description | Presentation for Black History Month |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Oral presentation at Cardiff City hall, in support of Black History Month, with the underlying theme being about 'Somali History and their contribution to Wales'. Ahmed Ali was asked to represent Cardiff's Somali community and to discuss how Science in Wales is helping both communities. He showed them some of the data produced on the anti-arthritic properties of Somali frankincense and the audience both Somali and Welsh truly appreciated the positive contribution of this research. |
| Year(s) Of Engagement Activity | 2011 |
| Description | Press Story on Cannabis and Schizophrenia - Matt Jones |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Lots of media attention as the result of a paper showing that cannabis disrupts brain connectivity in a similar way to that seen in schizophrenia. Articles published in many national newspapers including, The Times, The Daily Mail , The Sun and news websites worldwide. The fill list is below with links where available: Health Day News - US News and World report http://health.usnews.com/health-news/familyhealth/brain-and-behavior/articles/2011/10/25/pot-can-mimic-brain-changes-seen-in-schizophrenia Live Science http://www.livescience.com/16716-marijuana-schizophrenia-brain.html National News London The Times El Mundo http://www.elmundo.es/elmundosalud/2011/10/25/neurociencia/1319567670.html Nu.NL NRC Handelsblad (Dutch Newspaper) Australian Broadcasting Corportation Daily Mail http://www.dailymail.co.uk/health/article-2053486/One-cannabis-joint-bring-schizophrenia.html Big German wire service Service of Science News and Information, (Madrid) Metro International, world's largest global free daily newspaper http://www.metronews.ca/winnipeg/world/article/1006150--pot-use-knocks-the-orchestra-in-your-head-out-of-tune-study Press Association http://www.google.com/hostednews/ukpress/article/ALeqM5i3HK6el6_l-NZ-VF5_AlDqpcclEg?docId=N0272841319557869122A LA Times Gizmodo Australia http://www.gizmodo.com.au/2011/10/inside-your-brain-on-cannabis-cognitive-chaos/ Wired.com http://www.wired.com/wiredscience/2011/10/marijuana-brain-chaos/ International Business Times Australia http://au.ibtimes.com/articles/237667/20111026/cannabis-schizophrenic-marijuana-matt-jones-university-of-bristol-disorchestrated-michal-kucewicz.htm The Independent online http://www.independent.co.uk/life-style/health-and-families/health-news/cannabis-causes-chaos-in-the-brain-2376068.html MSN http://news.uk.msn.com/health/articles.aspx?cp-documentid=159585354 Yahoo News http://uk.news.yahoo.com/cannabis-disrupts-brain-waves-222420787.html Scinexx http://www.scinexx.de/wissen-aktuell-14038-2011-10-26.html ABC http://www.abc.es/20111026/sociedad/abci-cannabis-201110260001.html Ecoticias Europa Press http://www.europapress.es/salud/noticia-cannabis-podria-causar-especie-caos-cognitivo-cerebro-20111026101926.html Scotsman http://www.scotsman.com/news/health/cannabis_throws_brainwaves_into_chaos_1_1929411 New Kerala http://www.newkerala.com/news/2011/worldnews-94885.html The Sun Le Figaro Fox News http://www.foxnews.com/health/2011/10/26/cannabis-disrupts-brain-waves-like-schizophrenia-study-finds/ CBS News http://www.cbsnews.com/8301-205_162-20125822/solved-why-pot-smoking-causes-memory-loss/ New Scientist Mag - page 5 |
| Year(s) Of Engagement Activity | 2011 |
| Description | Press story Ahmed Ali Boswellia |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | In addition to the positive UK press / media coverage of this research the Somalia / Somaliland online press also gave positive coverage on this discovery with headlines such as "Somaliland Born Scientist finds a possible cure for arthritis using Somali frankincense" Articles publsihed in The Somaliland Press and Somali Diaspora News |
| Year(s) Of Engagement Activity | 2011 |
| Description | Press story Emma Blain Boswellia |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Press release which spraked considerable interest and was followed up by visit from a reporter, an interview and photo session for the local newspapers. Full page article published in the Western Mail, article in South Wales Echo with pictures and a short article in The Daily Mail. The story also appeared on news websites around the world. |
| Year(s) Of Engagement Activity | 2011 |
| Description | School Ambitions event at University of West of England |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | The event involved interactive discussions about science and novel therapeutics. None yet known |
| Year(s) Of Engagement Activity | 2011 |
| Description | School Careers Event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Oral presentation on careers given to year 12 students unknown |
| Year(s) Of Engagement Activity | 2011 |
| Description | School Visit BGS |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Two events, one presentation to school groups; second as a guest at the science prize giving to the whole school. Impact is to raise awareness of physical science and nanotechnology and how we can use it. |
| Year(s) Of Engagement Activity | 2011 |
| Description | School visit Wells |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | presented and discussed nanoscience to Wells Science and Engineering Club Impact is to raise awareness of physical science and nanotechnology and how we can use it. |
| Year(s) Of Engagement Activity | 2011 |
| Description | Science Cafe, Synthetic Biology, Dafydd Jones |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Keynote/Invited Speaker |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Around 45 members of the public attended the Science Cafe. at the Gate Arts Centre Cafe. The evening event included an informal lay presentation of research in Synthetic Biology followed by questions and discussion with the audience. The audience were very keen to participate in the discussion afterwards and enjoyed the event. |
| Year(s) Of Engagement Activity | 2012 |
| Description | TEDx at Bristol Event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | TEDx brings together creative thinkers and innovators. These live presentations are also available on the World Wide Web so audience figures are potentially global. This event had the theme of "the world around us" and the presentation was on the huge potential of nanotechnology to transform many aspects of our lives. |
| Year(s) Of Engagement Activity | 2011 |
| Description | Technologies in Translational Research and Development Event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Translational Research and Devlopment Event - One day meeting with a mixed audience including academic, commercial, government, nhs and technology transfer professionals. Has not yet taken place |
| Year(s) Of Engagement Activity | 2010 |
| Description | Wales Gene Park 6th form conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Talk about synthetic biology to around 1500 6th form students at St David's Centre in Cardiff, Enthusiastic feedback received from particpating schools. |
| Year(s) Of Engagement Activity | 2010 |
| Description | iSolve Project |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | The iSolve involves a group of students looking at the commercialisation possibilities of a real research project and presenting to an audience of Local business representatives, entrepreneurs and students The group won 1st prize. Impacts include involving students in commercialisation and stimulating the entreneurial and innovation culture within the University and encouraging contact with industry. |
| Year(s) Of Engagement Activity | 2010 |