DPFS Devolved Portfolio (Pilot).

Lead Research Organisation: King's College London

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

10 25 50
 
Description Circuits
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description DPFS
Amount £172,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2010 
End 08/2012
 
Title Arterial smooth muscle cell lines 
Description Immortalized versions of pulmonary arterial smooth muscle cells derived from control subject and a pulmonary arterial hypertension patient. 
Type Of Material Cell line 
Provided To Others? No  
Impact Cell lines suitable for downstream research 
 
Title Arterial stiffness database 
Description The database comprises measures of isobaric arterial stiffness in relation to patient characteristics such as 24 hour ambulatory blood pressure and target organ damage. It will be used to assess the discriminatory value of isobaric arterial stiffness with respect to hypertension severity as assessed by target organ damage. 
Type Of Material Biological samples 
Provided To Others? No  
Impact N/A 
 
Title Coincidence detection 
Description This is a DNA capture method reliant on two-component proximity to enable sensitive detection of proteins. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact nA 
 
Title Neuroimaging biomarkers 
Description MRI data 
Type Of Material Biological samples 
Provided To Others? No  
Impact NA 
 
Title V12RAS-zebrafish transgenic cell line: Model of mechanisms or symptoms - non-mammalian in vivo 
Description We have now established a breeding stock at KCL of this transgenic fish which has RAS driven tumour formation in the larval stage 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Provided To Others? No  
Impact NA 
 
Title joystick runway task 
Description The defensive model of anxiety can be used to explain behavior in a wide range of settings 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2011 
Provided To Others? Yes  
Impact Three TV programmes and a section in the popular science book The Psychopath Test by Jon Ronson. Also my work is cited highly enough to give me an H index of 7, ahead of what would be expected for a PhD graduate from 2009. 
 
Description Beerbaum-Chowyenczik 
Organisation Eindhoven University of Technology
Department Medical Physics
Country Netherlands 
Sector Academic/University 
PI Contribution a) We have performed MR-flow and catheter pressure measurements using a mechanical arterial model. The data has been used by Sheffield University to validate a data analysis tool. b) We have performed pulse-wave velocity measurements in phantoms, volunteers and patients which have been used for biophysical models of the cardiovascular system. c) We have performed measurements on a mechanical arterial model provided by TU- Eindhoven (Dr. Rutten). We have used this set-up for validation of new measurements techniques and cross-validation of different measurements. d) We have discussed the development of a new mechanical arterial model with University of Ghent, which has resulted in a grant application. e) We have developed a new Magnetic Resonance Imaging method to measure pulse wave velocity and evaluation tool which is used in clinical research to assess arterial stiffness in patients. f) We have tested the MRI-techniques implemented by Gyrotools
Collaborator Contribution a) Sheffield University has used our measurements to validate their analysis tool of aortic hemodynamics. b) Members of the Biophysical Engineering group have used data to validate biophysical models of the arterial system. This has resulted in the submission of papers and new grant proposal. c) The measurement of MR-flow and catheter pressures has resulted in discussion with TU-Eindhoven how to improve their mechanical model. d) We have discussed the development of a new mechanical arterial model with University of Ghent, which has resulted in a grant application. e) The measurement tools developed in this project are used in clinical research to assess arterial stiffness in patients. f) Potential commercialization of MR-measurement tools is discussed with Gyrotools. g) We have established a collaboration within the European Hypertension Society to examine the clinical applicability of the technology and to formulate a position statement on the measurement of isobaric arterial stiffness.
Impact - Paper submitted under review. - Grant proposal submitted to EPSRC under review. - MR-measurements part of clinical research protocols
Start Year 2011
 
Description Beerbaum-Chowyenczik 
Organisation GyroTools
Country Switzerland 
Sector Private 
PI Contribution a) We have performed MR-flow and catheter pressure measurements using a mechanical arterial model. The data has been used by Sheffield University to validate a data analysis tool. b) We have performed pulse-wave velocity measurements in phantoms, volunteers and patients which have been used for biophysical models of the cardiovascular system. c) We have performed measurements on a mechanical arterial model provided by TU- Eindhoven (Dr. Rutten). We have used this set-up for validation of new measurements techniques and cross-validation of different measurements. d) We have discussed the development of a new mechanical arterial model with University of Ghent, which has resulted in a grant application. e) We have developed a new Magnetic Resonance Imaging method to measure pulse wave velocity and evaluation tool which is used in clinical research to assess arterial stiffness in patients. f) We have tested the MRI-techniques implemented by Gyrotools
Collaborator Contribution a) Sheffield University has used our measurements to validate their analysis tool of aortic hemodynamics. b) Members of the Biophysical Engineering group have used data to validate biophysical models of the arterial system. This has resulted in the submission of papers and new grant proposal. c) The measurement of MR-flow and catheter pressures has resulted in discussion with TU-Eindhoven how to improve their mechanical model. d) We have discussed the development of a new mechanical arterial model with University of Ghent, which has resulted in a grant application. e) The measurement tools developed in this project are used in clinical research to assess arterial stiffness in patients. f) Potential commercialization of MR-measurement tools is discussed with Gyrotools. g) We have established a collaboration within the European Hypertension Society to examine the clinical applicability of the technology and to formulate a position statement on the measurement of isobaric arterial stiffness.
Impact - Paper submitted under review. - Grant proposal submitted to EPSRC under review. - MR-measurements part of clinical research protocols
Start Year 2011
 
Description Beerbaum-Chowyenczik 
Organisation University of Ghent
Department Institute of Biomedical Technology
Country Belgium 
Sector Academic/University 
PI Contribution a) We have performed MR-flow and catheter pressure measurements using a mechanical arterial model. The data has been used by Sheffield University to validate a data analysis tool. b) We have performed pulse-wave velocity measurements in phantoms, volunteers and patients which have been used for biophysical models of the cardiovascular system. c) We have performed measurements on a mechanical arterial model provided by TU- Eindhoven (Dr. Rutten). We have used this set-up for validation of new measurements techniques and cross-validation of different measurements. d) We have discussed the development of a new mechanical arterial model with University of Ghent, which has resulted in a grant application. e) We have developed a new Magnetic Resonance Imaging method to measure pulse wave velocity and evaluation tool which is used in clinical research to assess arterial stiffness in patients. f) We have tested the MRI-techniques implemented by Gyrotools
Collaborator Contribution a) Sheffield University has used our measurements to validate their analysis tool of aortic hemodynamics. b) Members of the Biophysical Engineering group have used data to validate biophysical models of the arterial system. This has resulted in the submission of papers and new grant proposal. c) The measurement of MR-flow and catheter pressures has resulted in discussion with TU-Eindhoven how to improve their mechanical model. d) We have discussed the development of a new mechanical arterial model with University of Ghent, which has resulted in a grant application. e) The measurement tools developed in this project are used in clinical research to assess arterial stiffness in patients. f) Potential commercialization of MR-measurement tools is discussed with Gyrotools. g) We have established a collaboration within the European Hypertension Society to examine the clinical applicability of the technology and to formulate a position statement on the measurement of isobaric arterial stiffness.
Impact - Paper submitted under review. - Grant proposal submitted to EPSRC under review. - MR-measurements part of clinical research protocols
Start Year 2011
 
Description Beerbaum-Chowyenczik 
Organisation University of Sheffield
Department Medical Physics Group
Country United Kingdom 
Sector Academic/University 
PI Contribution a) We have performed MR-flow and catheter pressure measurements using a mechanical arterial model. The data has been used by Sheffield University to validate a data analysis tool. b) We have performed pulse-wave velocity measurements in phantoms, volunteers and patients which have been used for biophysical models of the cardiovascular system. c) We have performed measurements on a mechanical arterial model provided by TU- Eindhoven (Dr. Rutten). We have used this set-up for validation of new measurements techniques and cross-validation of different measurements. d) We have discussed the development of a new mechanical arterial model with University of Ghent, which has resulted in a grant application. e) We have developed a new Magnetic Resonance Imaging method to measure pulse wave velocity and evaluation tool which is used in clinical research to assess arterial stiffness in patients. f) We have tested the MRI-techniques implemented by Gyrotools
Collaborator Contribution a) Sheffield University has used our measurements to validate their analysis tool of aortic hemodynamics. b) Members of the Biophysical Engineering group have used data to validate biophysical models of the arterial system. This has resulted in the submission of papers and new grant proposal. c) The measurement of MR-flow and catheter pressures has resulted in discussion with TU-Eindhoven how to improve their mechanical model. d) We have discussed the development of a new mechanical arterial model with University of Ghent, which has resulted in a grant application. e) The measurement tools developed in this project are used in clinical research to assess arterial stiffness in patients. f) Potential commercialization of MR-measurement tools is discussed with Gyrotools. g) We have established a collaboration within the European Hypertension Society to examine the clinical applicability of the technology and to formulate a position statement on the measurement of isobaric arterial stiffness.
Impact - Paper submitted under review. - Grant proposal submitted to EPSRC under review. - MR-measurements part of clinical research protocols
Start Year 2011
 
Description CRT Denmark 
Organisation August Pi i Sunyer Biomedical Research Institute
Department Hospital Clinic of Barcelona
Country Spain 
Sector Hospitals 
PI Contribution Psychiatric Centre Copenhagen - CIRCuiTS is currently being translated into Danish to use in a large RCT investigating the use of CIRCuiTS to enhance supported employment. We have provided the use of CIRCuiTS, and offered advice regarding measurement of the process of therapy and therapist fidelity. CRT Spain and Canada: We have provided the use of CIRCuiTS and training in its use. Til Wykes is a co-applicant on a grant for an RCT of CRT for adolescents.
Collaborator Contribution They have translated CIRCuiTS into Danish and paid for the cost of this work. CRT Spain: They have translated CIRCuiTS into Spanish. CRT Canada: Translated CIRCuiTS into French and made adaptations for adolescent groups. Caroline Cellard is the lead applicant for funding for an RCT.
Impact New versions of CIRCuiTS in Danish, Spanish and French.
Start Year 2010
 
Description CRT Denmark 
Organisation University of Laval
Country Canada 
Sector Academic/University 
PI Contribution Psychiatric Centre Copenhagen - CIRCuiTS is currently being translated into Danish to use in a large RCT investigating the use of CIRCuiTS to enhance supported employment. We have provided the use of CIRCuiTS, and offered advice regarding measurement of the process of therapy and therapist fidelity. CRT Spain and Canada: We have provided the use of CIRCuiTS and training in its use. Til Wykes is a co-applicant on a grant for an RCT of CRT for adolescents.
Collaborator Contribution They have translated CIRCuiTS into Danish and paid for the cost of this work. CRT Spain: They have translated CIRCuiTS into Spanish. CRT Canada: Translated CIRCuiTS into French and made adaptations for adolescent groups. Caroline Cellard is the lead applicant for funding for an RCT.
Impact New versions of CIRCuiTS in Danish, Spanish and French.
Start Year 2010
 
Description CRT manchester 
Organisation University of Manchester
Department Manchester Academic Health Science Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution CRT Manchester: Provision of the use of CIRCuiTS; consulatation on trial conduct; collaboration to produce paper (submitted to Schizophrenia Bulletin)
Collaborator Contribution CRT Manchester: Conducted RCT of CRT or TAU plus CBT.
Impact Paper for CRT Manchester submitted to Schizophrenia Bulletin.
Start Year 2009
 
Description Cognitive remediation for borderline personality disorder 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Lead applicant - Clare Reeder
Collaborator Contribution Paul Moran - co-applicant
Impact grant application submitted for CRT for BPD.
Start Year 2012
 
Description Cognitive remediation within early intervention services (CRT for EI) 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Application in progress for programme grant to assess new modes of delivery of CRT (using CIRCuiTS as the basis) in multi-centre national early intervention trial. Lead applicant - Til Wykes; Applicant - Clare Reeder
Collaborator Contribution co-applicant
Impact programme application underway for CRT for early intervention services
Start Year 2011
 
Description Integrating multiple modalities (LONI laboratory) 
Organisation University of California, Los Angeles (UCLA)
Department LONI Laboratory of Neuro Imaging
Country United States 
Sector Academic/University 
PI Contribution We have collected the neuroimaging and clinical data, and a researcher from our team will have a 3 month placement in the LONI laboratory to implement their pipeline in the analysis of our data.
Collaborator Contribution The LONI lab is internationally known for their development of innovative methods of analysis of neuroimaging data. They will provide the pipeline for the analysis and implement it so that can be used with our data.
Impact Thanks to the collaboration, our researcher was awarded a Young Investigator Award from NARSAD to conduct the work.
Start Year 2010
 
Description University of Bonn 
Organisation University of Bonn
Country Germany 
Sector Academic/University 
PI Contribution I provided the creative content: I invented the Joystick Operated Runway Task.
Collaborator Contribution Prof Ettinger acted as a sounding board for experimental ideas and helped refine the task and the experimental design.
Impact Perkins, A. M., Ettinger, U., Weaver, K., Schmechtig, A., Schrantee, A., Morrison, P. D., Sapara, A., Kumari, V., Williams, S. C. R., & Corr, P. J. (in review). Advancing the defensive explanation for anxiety disorders: lorazepam effects on human defense are systematically modulated by personality and threat-type. Translational Psychiatry. Perkins, A. M., Ettinger, U., Williams, S. C. R., Reuter, M., Hennig, J., & Corr, P. J. (2011). Flight behaviour in humans is intensified by a candidate genetic risk factor for panic disorder: evidence from a translational model of fear and anxiety. Molecular Psychiatry,16, 242-244. Perkins, A. M., Ettinger, U., Davis, R., Foster, R., Williams, S. C. R., & Corr, P. J. (2009). Effects of lorazepam and citalopram on human defensive reactions: Ethopharmacological differentiation of fear and anxiety. Journal of Neuroscience, 29, 12617-12624.
Start Year 2007
 
Description manchester University 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution Developing a novel siRNA vector system for zebrafish
Collaborator Contribution Provision of reagents and expert advice
Impact NA
Start Year 2007
 
Description • Clinical service for complex neurofibromatosis 1 
Organisation Cardiff University
Department Cancer and Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution • We are sending blood and tumour tissue to Prof Upadhyaya from participants in the MET PET CT study. She will look for molecular markers of NF1-MPNST. Potentially this will improve diagnosis and facilitate targeted treatment
Collaborator Contribution • Cardiff collaboration will look at molecular markers of NF1-MPNST in blood and tumour tissue
Impact • Cardiff - molecular biology, neurology, PET, peripheral nerve/neurosurgery
Start Year 2011
 
Description • Evaluation of MET PET CT in diagnosing neurofibromatosis 1 (NF1) -MPNST 
Organisation Manchester University NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution • We have invited the Manchester team to recruit participants for the MET PET CT study and to refer them to our centre. They will follow-up participants long-term in the Manchester neurofibromatosis service
Collaborator Contribution • Manchester collaborators are contributing participants to the MET PET study and data to the clinical study
Impact • Manchester - collaboration is multi-disciplinary (neurology, PET genetics, paediatrics, neurosurgery, peripheral nerve surgery, oncology, psychiatry)
Start Year 2009
 
Title Aortic Pulse Wave Velocity Measurement 
Description Our new approach allows non-invasive assessment of hypertension, which is one of the most important causes of global morbidity and mortality in the developed world with a significant socio-economic burden. One of the primary clinical issues of hypertension is that current diagnoses are largely based on thresholds of blood pressure and the assessment of haemodynamic waveforms. The patent application describes the assessment of arterial stiffness through real-time measurement of pulse-wave velocity (with Doppler, Tonography or MRI) while modulating intrathoraic pressure by breathing maneuvers. 
IP Reference WO2013110929 A1 
Protection Patent application published
Year Protection Granted 2013
Licensed No
Impact N/A
 
Title CIRCuiTS - Computerised Remediation of Cognition - Training for Schizophrenia 
Description This is novel computerized psychological therapy for people with a diagnosis of schizophrenia which aims to improve thinking skills such as attention, memory and problem-solving. 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2011
Licensed Yes
Impact Currently being used in a number of RCTs of CRT across the world (see above).
 
Title Circuits 
Description Computer software for Cognitive Remedial Therapy 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2011
Licensed No
Impact Software is being evaluated in a RCT
 
Title coincidence detection 
Description This is a DNA capture method reliant on two-component proximity to enable sensitive detection of proteins. 
IP Reference WO2011161420 
Protection Patent application published
Year Protection Granted 2011
Licensed No
Impact NA
 
Title A Repeatable and Objective Behavioural Assay of Anxiety in Humans 
Description The Joystick Operated Runway Task is now being tested with anxiety patients with a view to being used to characterize treatment response. 
Type Support Tool - For Medical Intervention
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2011
Development Status Under active development/distribution
Impact We have proved the joystick task is sensitive to the established anti-anxiety drug lorazepam so the task can now be used to test new drugs for anti-anxiety properties 
 
Title Antithrombotic agent for the prevention of antibody mediated rejection in renal transplantation 
Description "This project seeks to establish the feasibility of using a novel class of antithrombotic agents - cytotopic thrombin inhibitors - in transplantation. The clinical target is antibody-mediated acute rejection (AMR). This can arise because potential recipients of grafts have pre-existing antibodies against blood group (ABO) or human leukocyte antigens in the donated organ. At least 15% of potential recipients are denied transplantation for this reason and some manifestation of AMR is estimated to occur in 10-15% of renal transplants. AMR involves activation of the classical pathway of the complement system but this system interacts with coagulation pathways so that complement activation and thrombotic consequences go hand in hand. Thrombosis treated with anticoagulants given systemically is associated with a bleeding risk which is generally unacceptable in transplant surgery. Building on a chemical strategy which has been applied successfully to modified complement regulatory molecules, we have prepared novel inhibitors of thrombin which can be anchored to the vascular surface in organs by perfusion prior to transplantation. This permits the graft rather than the recipient patient to be anticoagulated. We have used an animal model of AMR in which sensitised rats rapidly reject transplanted kidneys. Preliminary results with a locally perfused lead compound have suggested that graft survival can be prolonged under conditions that avoid a major risk of bleeding. We are seeking support to validate this conclusion and to investigate if combination with complement inhibitors provides added benefit. 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 Circuits 
Description We are currently undertaking early clinical assessment in a feasibility RCT (n=120) funded by a RfPB grant (see above). Also, being assessed in various other RCTs around the world. Current pilot feasibility data being collected using different methods of delivery (e.g. in groups). 
Type Therapeutic Intervention - Psychological/Behavioural
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2011
Development Status Under active development/distribution
Impact The program is currently being tested in a RCT. This CRT programme is unique in (a) having clear theoretical underpinnings; (b) being specifically designed for a schizophrenia patient group; (c) incorporating a metacognitive therapeutic stance; (d) incorporating a clear role for therapists; (e) being easily translatable and already translated into several languages. 
 
Title Computerised cognitive remediation therapy programme for schizophrenia 
Description "Cognitive Remediation Therapy (CRT) improves cognitive and social functioning in schizophrenia, but reliance on intensive therapist input limits its implementation within the NHS. Computerised CRT reduces therapist burden but existing packages have not been designed for schizophrenia. CIRCuiTS is a new, ecologically-valid, graphically and functionally sophisticated computerised CRT programme, driven by clear theoretical principles and relies on well-researched training techniques for schizophrenia. The software is complete, but its feasibility and acceptability, particularly in relation to its method of delivery and dose of treatment have not been assessed. This study will investigate: (a) the acceptability and feasibility of CIRCuiTS for a wide range of cognitive and computer abilities; (b) the extent to which patients need therapist assistance; (c) any therapist interface difficulties that might arise (d) the levels of within-therapy change that impact on outcome cognitive change to provide therapists with a within-therapy goal for task change. Feedback from this study will result in a refined therapeutic manual so that the programme will be ready to be tested in clinical trials. Most recent work supported by DPFS Portfolio Award" 
Type Therapeutic Intervention - Psychological/Behavioural
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2011
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Still in development 
 
Title Detection and characterisation of Clostridium difficile in diarrhoeal stools 
Description "This is academic/industry collaboration between KCL, Brandeis University and Smiths Detection. Clostridium difficile (CD) is a major cause of hospital/healthcare outbreaks of diarrhoea, associated with significant morbidity and mortality. CD causes disease by production of toxins A and B (encoded by genes tcdA, tcdB). Recent outbreaks have been due to virulent strains, most commonly ribotype 027, which produces an additional binary toxin (encoded by cdtA, cdtB) and hyperproduces toxin because of variation in the repressor gene tcdC. Rapid diagnosis is essential for patient management and infection control. Diagnosis is usually by Enzyme Immuno-Assay (EIA) of toxins A and B, but performance of present kits is unsatisfactory. Detection of glutamate dehydrogenase (GDH) is more specific but does not distinguish toxigenic from non-toxigenic strains. One commercial PCR system for detection of genes for B and binary toxins and one genetic variation in tcdC has been announced performance data are limited. There is a need for a rapid test to simultaneously detect genes for toxins A/B and binary, toxin hyperproduction and CD type. We propose to develop such a test using the Smiths Bioseeq automated LATE-PCR system, which allows complex multiplexing and can be run safely by non-specialised staff in non-laboratory settings. Most recent work supported by DPFS Portfolio Award" 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2011
Development Status Closed
Impact tbc 
 
Title ESTABLISHING EARLY NEUROIMAGING BIOMARKERS TO PREDICT TREATMENT RESPONSE IN SCHIZOPHRENIA 
Description The findings of this study are pointing to the presence of neuroanatomical markers that could be used as early predictors of response to treatment and outcome. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2012
Development Status Actively seeking support
Impact NA 
 
Title Fluorescent zebrafish model of invasive melanoma 
Description "Melanoma is an increasingly common cancer with high mortality and there are currently no high throughput animal models of growth and invasion. Zebrafish is an ideal vertebrate model system for target validation and inhibitor screening where the aetiology and pathogenesis of cancer in zebrafish mirrors that in mammals. We wish to demonstrate that our zebrafish melanoma model can be used for target validation and as a drug-discovery tool using PAK4 as a proof of principle. Our model is published and validated as representative of human disease and has an advantage over previous zebrafish models because aberrant melanocyte proliferation occurs at an early larval stages which makes it amenable to high through put analysis. Tumour growth can be monitored by quantification of melanin expression and the fluorescently labelled tumour cells can be imaged in real time. We are seeking funds to strengthen our DPFS full proposal by 1. Generating a V12Ras vector with a commercially acceptable Green flourescent protein (GFP). We can then use this vector to establish a new zebrafish line at KCL as soon as we have full funding - this will significantly advance the project 2. Develop quantitative high-through-put analysis protocols for tumour growth and invasive behaviour - this will strengthen the unique aspects of the project proposal. 3. Identify siRNA sequences to knockdown zebrafish PAK4 - this will progress the proof of concept element of our proposal. 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 
 
Title Multiplex, coincidence detection of biomarkers 
Description "A significant challenge of biomedical translational research is the identification of molecular biomarkers that can be used in diagnosis, prognosis and in predicting and evaluating responses to treatments. The reliable assessment of these biomarkers in biological samples, particularly those from the clinic, has proved challenging; immunohistochemistry in this context has been poorly controlled, minimally quantified and lacking in the specificity required. Prior work has established that an optical, coincidence detection approach can drive specificity to yield spatially resolved, robust and meaningful patient data. We have now translated the principle of coincidence detection into a novel coincidence biodetector that has been tested successfully as a coincidence readout. Through the generation of a small repertoire of recombinant detectors fused to this novel coincidence readout, we now propose to establish the proof of concept for this biomarker approach 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 NOGO Receptor ( NgR1) inhibitors for Brain Repair 
Description "The Nogo receptor 1 (NgR1) limits regeneration in the damaged nervous system and has been identified as a therapeutic target for a wide range of conditions including motor neuron disease (MND/ALS). A number of pharmaceutical companies have programmes to develop biological agents (e.g. antibodies) that inhibit NgR1 function (Biogen, Novartis and GSK). We have used virtual screening to identify the first small drug-like NgR1 inhibitors; however, for reasons discussed in section 4.2 below we would like to identify additional hits to advance this programme. To this end we have used similar in silico techniques to identify ~100 compounds that are closely related to the existing hits, as well as ~100 novel candidates all from the ChemBridge library of 800,000 compounds. The aim of this project is to obtain evidence that our "in-house" approach can identify novel selective NgR1 antagonists, and to use this as the starting point for seeking funding for a major drug discovery programme. 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 tbc 
 
Title Novel, non-invasive clinical tool to provide a patient-specific measure of isobaric aortic stiffness in hypertensive patients 
Description "Need: Hypertension contributes to approximately 50% of all cardiovascular deaths (estimated 8 million deaths/year worldwide), the vast majority attributable to systolic hypertension which is related to stiffening of the aorta and great arteries. Recent studies have shown that lowering blood pressure does not normalise aortic stiffness. However, there is no clinical tool currently available to specifically assess the aortic stiffness, independent of blood pressure, for an individual patient. Solution: We will design and clinically validate a novel tool for clinical use to measure aortic stiffness through an innovative application of magnetic resonance imaging technology. Rationale: To identify high-risk individuals and tailor drug treatment aiming specifically at reducing large artery stiffness and hence mortality/morbity. Development plan: Implementation and validation of realtime MR flow techniques, providing an integrated PC-unit to display changing pulse wave velocity versus physiological parameters in real time and clinical study in hypertensive patients. s 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 Therapeutic resolution of BMPR2 mediated signalling defects in pulmonary arterial hypertension (PAH) 
Description "PAH is a devastating cardiovascular disorder caused by extensive vascular remodelling of blood vessels in the lung and in the absence of effective therapy, leads to right-heart failure (1). We have demonstrated that heterozygous nonsense mutation in the type II receptor (BMPR-II) for bone morphogenetic proteins, underlie the majority of the inherited and familial forms of PAH (2). The principle aim of this project is to develop a therapy for PAH by promoting translation readthrough of pathogenic nonsense alleles using non-toxic chemical agents. Current systems are not suitable for high-throughput screening, thus we have developed a dual-fluorescence reporter assay. We now seek to enhance the development of this assay and use it to identify small molecules capable of resolving BMPR2 mediated signalling defects. Studies performed in mammalian cells and a mouse model will provide proof of principle for restoration of receptor mediated signalling by demonstrating therapeutic effecacy prior to and following the onset of PAH 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 Treg sub-populations in patients with advanced kidney disease for induction of transplant tolerance 
Description A regulatory T cell based cell product for use in clinical trials. Most recent funding is via the EU Consortium, as above. 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2012
Development Status Under active development/distribution
Impact tbc 
 
Title [11]C-methionine positron emission computerised tomography in diagnosing neurofibromatosis 1 
Description "Neurofibromatosis 1 (NF1) is a complex inherited disease that involves the skin and nervous system predominantly and predisposes affected individuals to the development of benign and malignant tumours. It is characterised by multiple benign peripheral nerve sheath tumours (neurofibromas). Affected individuals have a 7%-13% life-time risk of developing malignant peripheral nerve sheath tumours (MPNSTs) that ususally arise from benign plexiform neurofibromas. MPNST are challenging to diagnose and treat, frequently heralding a poor prognosis. Magnetic resonance imaging (MRI) shows the site and extent of the tumour but is not a reliable indicator of malignancy. [18]-F-fluorodeoxyglucose positron emission computerised tomography (FDG PET-CT) has enabled the selection of patients likely to have MPNST by virtue of the increased metabolic activity of the tumours, but demonstrates an overlap between benign and malignant tumours, necessitating potentially hazardous diagnostic surgery. Sensitive and specific diagnostic imaging is essential to predict MPNST grade and prognosis and to permit monitoring of response to drug therapy. [11]C- methionine PET (MET PET) will be evaluated as a diagnostic tool for NF1-MPNSTs to determine its' superiority to FDG PET. MET and FDG PET findings will be compared with tumour histology (microscopic structure) to determine its ability to predict tumour grade and prognosis. 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