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).

Publications

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Azzopardi E (2013) Colistin past and future: A bibliographic analysis in Journal of Critical Care

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Azzopardi EA (2013) Colistin in burn intensive care: back to the future? in Burns : journal of the International Society for Burn Injuries

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Azzopardi EA (2013) The enhanced permeability retention effect: a new paradigm for drug targeting in infection. in The Journal of antimicrobial chemotherapy

 
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 03/2013 
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 06/2013 
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 05/2013 
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 09/2012 
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 03/2013 
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 09/2013 
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 09/2012 
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 AlgiPharma - Ferguson 
Organisation AlgiPharma
Country Norway 
Sector Private 
PI Contribution Testing of Polymers produced by the collaborator, Research and development testing conjugation properties
Collaborator Contribution Fund the collaboration and supply polymers for research and testing
Impact Production of innovative polymers. Two major applications for collaborative research in progress.
Start Year 2007
 
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 Compton Group - Department of Chemistry 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution The research team bring the biology and arthritis model expertise. Ahmed Ali works at the University woth use of all facilities.
Collaborator Contribution In kind contribution of Ahmed Ali full time
Impact The tests funded by SARTRE were carried out to test the anti-inflammatory properties of extracts of Boswellia frereana, commonly known as Somali frankincense, in a murine model of acute Sodium Dextran Sulphate - induced colitis inflammation. Over a period of 7 days the plant extract significantly reduced the clinical symptoms associated with colitis related inflammation, such as loss in body weight, clinical scores and stool scores when compared to the saline control group. After day 8 the Boswellia frereana extract continued to have a significant effect on body weight loss and colon shortening whilst no significant effect was observed for the clinical and stool scores compared to the saline control group. This promising data assisted The Compton Group in out licensing the patent application to an American group, which is led by the Head of Research and Development of a pharmaceutical company which has a market capitalisation of approximately US $ 25 billion. The present state of play is that the American group and Compton Group are organising the manufacture and clinical testing of 50,000 nutraceutical capsules with Boswellia frereana as the main ingredient. Should the IP generate revenue, a royalty will be payable back to Cardiff University IP jointly owned Multidisciplinary collaboration - Ahmed Ali provides chemistry expertise, Academic team have biology expertise.
 
Description GE Healthcare 
Organisation GE Healthcare Limited
Department Life Sciences
Country United Kingdom 
Sector Private 
PI Contribution Expertise in viral infection and propogation
Collaborator Contribution Use of their microscopy facilities
Impact Research partnership
Start Year 2013
 
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 Jones and Collinson, Bristol 
Organisation University of Bristol
Department School of Biochemistry Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in non-natural amino acid insorporation
Collaborator Contribution Expertise in membrane proteins
Impact Submitted a grant application for a joint PhD studentship
Start Year 2013
 
Description Jones and Main, Queen Mary 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Working on a project entitled - Directed protein fibre self-assembly through non-native amino acid incorporation and click chemistry.
Collaborator Contribution Expertise in repeat protein and fibres
Impact Gained EPSRC funding through the directed assembly network to develop the idea
Start Year 2013
 
Description Jones and Stultz Southampton 
Organisation University of Southampton
Department Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Working on project entitled Precision attachment of proteins in DNA origami tiles through click chemistry. Our expertise is in Click chemistry and protein enginneering
Collaborator Contribution Expertise in attachment of proteins and DNA origami
Impact EPSRC funding to develop proeject
Start Year 2013
 
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 MRCT - Calpain inhibitor project 
Organisation MRC-Technology
Department Small Molecules Discovery Unit
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Provision of expertise, research materials (protein and mercaptoacrylate inhibitors) and animal models of arthritis.
Collaborator Contribution Provision of expertise and medicinal chemistry input - advanced screening and development. Feasibility studies and follow up screening carried out.
Impact Fluorescent inhibitor analogue produced for use in competitive screening assay. Preliminary data produced with the aim of applying for a collaborative grant to develop clinical candidate for treatment of rheumatoid arthritis. Disciplines include inflammation biology, animal models of arthritis and synthetic and medicinal chemistry.
Start Year 2011
 
Description Nanotether Discovery Science with Dafydd Jones 
Organisation Nanotether Discovery Science Ltd
Country United Kingdom 
Sector Private 
PI Contribution Ongoing collaboration related to site-specific post-translational modification of proteins (protein kinases specifically) with auxiliary molecules with the aim of high-throughput protein interaction screening. The approach uses genetically encoded azido chemistry incorporated into a target protein at a site amenable to post-translational modification without adversely effecting protein function using bioorthongonal Click Chemistry approaches. The collaboration involves consultations and exchanges of staff, materials and expertise with regards to non-natural amino acid incorporation into proteins and the subsequent Click Chemistry modification of proteins.
Collaborator Contribution NDS have funded the collaboration and are active in consultations and exchanges of staff, materials and expertise.
Impact Novel protein kinase variants have been made for use as research tools on the project.
Start Year 2012
 
Description University of Southampton with Dafydd Jones 
Organisation University of Southampton
Department Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Site specific conjugation of proteins to DNA. The approach uses genetically encoded azido chemistry incorporated into a target protein at a site amenable to modification with DNA. The approach uses bioorthonganol Click Chemistry approaches. The ultimate aim is to control protein position and orientation in "DNA origami" based molecular assembly processes.
Collaborator Contribution Input on DNA origami approach and molecular assembly processes.
Impact Knowledge sharing and exchange of ideas. Development of novel research tools
Start Year 2012
 
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