Cambridge Confidence in Concepts: translating pathophysiological insights for patient benefit
Lead Research Organisation:
University of Cambridge
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
The Confidence in Concept scheme is a key part of MRC’s translational research strategy and provides annual awards to institutions, to be used flexibly to support the earliest stages of multiple translational research projects. The award can be used by the institution to support a number of preliminary-stage translational projects. The projects supported should aim to provide sufficient preliminary data to establish the viability of an approach –– before seeking more substantive funding. It is intended to accelerate the transition from discovery research to translational development projects by supporting preliminary work or feasibility studies to establish the viability of an approach.
Publications
Costopoulos C
(2016)
TCT-598 Plaque rupture in coronary atherosclerosis is associated with increased plaque structural stress
in Journal of the American College of Cardiology
Costopoulos C
(2017)
Plaque Rupture in Coronary Atherosclerosis Is Associated With Increased Plaque Structural Stress
in JACC: Cardiovascular Imaging
De Sciscio P
(2017)
Quantifying the Shift Toward Transcatheter Aortic Valve Replacement in Low-Risk Patients: A Meta-Analysis.
in Circulation. Cardiovascular quality and outcomes
Douglas GR
(2017)
Impact of Fiber Structure on the Material Stability and Rupture Mechanisms of Coronary Atherosclerotic Plaques.
in Annals of biomedical engineering
Goebbels S
(2017)
A neuronal PI(3,4,5)P3-dependent program of oligodendrocyte precursor recruitment and myelination.
in Nature neuroscience
| Description | Application by CMI Ltd |
| Amount | £40,000 (GBP) |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2020 |
| Description | BHF Translational Award |
| Amount | £248,018 (GBP) |
| Funding ID | TG/15/4/31891 |
| Organisation | British Heart Foundation (BHF) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | CRUK Pioneer Award |
| Amount | £193,312 (GBP) |
| Organisation | Cancer Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2017 |
| Description | Cambridge-Africa Alborada Research Fund |
| Amount | £19,852 (GBP) |
| Organisation | Alborada Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2017 |
| Description | Cambridge/GSK Varsity Initiative |
| Amount | £448,865 (GBP) |
| Organisation | GlaxoSmithKline (GSK) |
| Sector | Private |
| Country | Global |
| Start | |
| Description | Clinical Research Training Fellowship |
| Amount | £116,678 (GBP) |
| Organisation | British Heart Foundation (BHF) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2016 |
| End | 08/2019 |
| Description | Development of direct stapled peptide inhibitors of Ras proteins |
| Amount | £62,000 (GBP) |
| Organisation | Cambridge Cancer Centre |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 06/2016 |
| Description | Emergency Award Grant |
| Amount | £22,050 (GBP) |
| Funding ID | 900248 |
| Organisation | ACT |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 04/2020 |
| Description | Enterprise Fellowship "Cambridge Cardiology: Developing Catheter-based Treatments for Valvular Heart Disease" |
| Amount | £60,000 (GBP) |
| Organisation | Royal Academy of Engineering |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2017 |
| End | 02/2018 |
| Description | European Research Council Horizon 2020 |
| Amount | € 1,400,000 (EUR) |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 07/2017 |
| Description | Gates Scholarship |
| Amount | £130,000 (GBP) |
| Organisation | Bill and Melinda Gates Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 09/2017 |
| Description | HEFCE |
| Amount | £204,392 (GBP) |
| Organisation | Higher Education Funding Council for England |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| End | 03/2018 |
| Description | Inward potassium conductance of the oligodendrocyte precursor cells in failure and success of myelin regeneration |
| Amount | £9,983 (GBP) |
| Organisation | University of Cambridge |
| Department | Isaac Newton Trust |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2021 |
| End | 11/2021 |
| Description | Mitochondrial Medicine |
| Amount | £550,000 (GBP) |
| Funding ID | MC_UU_00015/5 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 12/2019 |
| Description | Molecular mechanisms of bile salt export pump (ABCB4) inhibition |
| Amount | £88,210 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2015 |
| End | 09/2019 |
| Description | Molecular mechanisms of bile salt export pump (ABCB4) inhibition. |
| Amount | £58,484 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2019 |
| End | 09/2020 |
| Description | NEURONAL REGULATION OF CNS MYELIN PLASTICITY |
| Amount | £1,769,672 (GBP) |
| Organisation | European Commission H2020 |
| Sector | Public |
| Country | Belgium |
| Start | 05/2018 |
| End | 05/2023 |
| Description | NHS Blood and Transplant (NHSBT) |
| Amount | £320,270 (GBP) |
| Organisation | National Health Service |
| Sector | Hospitals |
| Country | United Kingdom |
| Start | |
| Description | NIHR Invention for Innovation Challenge Award |
| Amount | £536,627 (GBP) |
| Organisation | National Institute for Health Research |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2017 |
| Description | Repair of the corticospinal tract |
| Amount | £638,866 (GBP) |
| Funding ID | MR/R004463/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2018 |
| End | 12/2020 |
| Description | Repurposing AMPAkines for enhancing myelin regeneration in multiple sclerosis |
| Amount | £130,000 (GBP) |
| Funding ID | 204488/Z/16/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2017 |
| End | 01/2021 |
| Description | SALARY SUPPORT: |
| Amount | £7,303 (GBP) |
| Organisation | Cambridge University Hospitals NHS Foundation Trust |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2016 |
| End | 03/2016 |
| Description | Spinal cord repair: releasing the neuron-intrinsic brake on axon regeneration |
| Amount | £236,008 (GBP) |
| Funding ID | MR/R004544/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2017 |
| End | 04/2020 |
| Description | Structure function relationships in the Breast Cancer Resistance Protein (ABCG2) |
| Amount | £110,000 (GBP) |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2020 |
| Description | The Biomedical Catalyst: Regenerative Medicine Research Committee (RMRC) |
| Amount | £208,259 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2016 |
| End | 12/2019 |
| Description | The role of membrane potassium conductance of oligodendrocyte precursor cells in age-related decline in myelination |
| Amount | £45,000 (GBP) |
| Organisation | University of Cambridge |
| Department | Isaac Newton Trust |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2019 |
| End | 09/2021 |
| Description | Translational Research Award |
| Amount | £109,776 (GBP) |
| Organisation | Heart Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2016 |
| End | 05/2018 |
| Description | WHY ARE T REGULATORY CELLS FROM INDIVIDUALS WITH MULTIPLE SCLEROSIS DEFECTIVE AND CAN THEIR FUNCTION BE RESTORED |
| Amount | £73,500 (GBP) |
| Organisation | Rosetrees Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2019 |
| Description | Wellcome Trust Beit Prize Grant |
| Amount | £26,414 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | exploring how the C terminus of RalA regulates its structure and function |
| Amount | £44,348 (GBP) |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2020 |
| Description | exploring how the C terminus of RalA regulates its structure and function |
| Amount | £96,696 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2020 |
| Description | framework s'ship: structural and functional studies of the machinery of bacterial riboregulation |
| Amount | £122,390 (GBP) |
| Organisation | AstraZeneca |
| Sector | Private |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2020 |
| Description | reconstruction of sensory pathways |
| Amount | £120,968 (GBP) |
| Organisation | International Foundation for Research in Paraplegia (IRP) |
| Sector | Charity/Non Profit |
| Country | Switzerland |
| Start | 08/2017 |
| End | 08/2019 |
| Description | successor to the CRUk funded PRAM-GBM study |
| Amount | £391,457 (GBP) |
| Organisation | Cancer Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | the machinery of rna metabolism and riboregulation in bacteria |
| Amount | £1,630,519 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2016 |
| End | 07/2021 |
| Description | Collaboration with Mr Tsui (Consultant Surgeon Papworth Hospital) |
| Organisation | Papworth Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | provided clinical input with respect to operative requirements and tissue prosthesis interaction. |
| Collaborator Contribution | He brought considerable experience in preclinical development as a scientific advisor for class III device manufacturers including Thoratec Corp. |
| Impact | N/A |
| Start Year | 2016 |
| Title | A new method based on fluorescence for measuring 4MU levels in the brain |
| Description | The studies of 4MU in animals were performed with pharmaceutical grade compound obtained through an agreement with DB Pharma in France, who market 4MU as Cantabiline. This agreement is with the University of Leeds, which is where Jessica Kwok now works. The agreement gives a free supply of the compound in exchange for regular updates on progress, and first option on commercialization of future IP. A patent application has been made by the University of Leeds for use of 4MU in the treatment of spinal cord injury. |
| Type | Therapeutic Intervention - Drug |
| Year Development Stage Completed | 2020 |
| Development Status | Under active development/distribution |
| Impact | The papers describing this work will be submitted within the next 6 months. At this point we will decide whether further animal work is needed to optimise treatment with the compound. The current data are now sufficient to apply for a grant to cover a full toxicology package and a phase1 study in humans. |
| Title | Digi-Vis": an all-in-one digital visual function assessment system |
| Description | The Covid crisis accelerated and modified the programme of development of DigiVis. The clinical need for an accurate self-test VA system to support remote consultation was clear. With additional funding from Addenbrooke's Charitable Trust, the code was rewritten and redesigned to enable self-testing at home as a web-app rather than a pre-loaded windows app. Two IRAS approved clinical validation studies, started in September 2020, have now been completed and published. The results show excellent test-retest reliability and accuracy compared to standard VA testing in clinic and extremely good patient feedback with >90% of patients rating DigiVis good or excellent. Two service evaluations demonstrating firstly a doubling in capacity in orthoptic clinics by using DigiVis for remote consultation and also its potential use in general paediatric clinics have been presented at national conferences. |
| Type | Therapeutic Intervention - Medical Devices |
| Year Development Stage Completed | 2021 |
| Development Status | Under active development/distribution |
| Impact | DigiVis has been translated into clinical use at CUHFT Cambridge Enterprise (currently free of charge until the licence is signed). It was used from March to September 2021 by the Cambridgeshire and Peterborough Combined Authority for catch up vision screening for the 20,000 children who had missed out due to school closures. DigiVis will enable ophthalmology departments to move towards the NHS Long Term Plan goal of 30% remote consultations by supporting video consultations and enabling patients to monitor their own vision at home. An increased number of remote consultations will help to deal with the severe backlog in ophthalmology clinics. It is estimated that 3000 patients have lost vision avoidably over the course of the Covid pandemic due to delayed appointments. DigiVis will enable the 50% Local Authorities who currently do not undertake the nationally recommended reception year school vision screening, to do so in a cost-effective manner without the need for trained screeners. This will reduce health equality and reduce the risk of avoidable visual impairment in children. DigiVis will enable home self-monitoring of vision for patients at risk of visual deterioration or as a monitor for therapy. DigiVis will make vision screening possible in children attending general paediatric clinics both to detect the 20% of children with unsuspected refractive error and to enable early detection of eye pathology in children at risk of eye disease due to systemic or neurological disease. |
| URL | https://www.elystandard.co.uk/news/new-eye-test-technology-launched-for-cambs-7822680 |
| Title | reproducible crystallographic system for validation of fragments |
| Description | We have now reproducible crystallographic system for validation of fragments on the target site and number of active fragments which can be improved by structure guided design. We have also biophysical assays that can be used for analysis of new compounds. We have also constructs for eventual cellular studies to test membrane binding of PH domain and its disruption with small molecules. In the end none of the hits proved tractable and we were unable to obtain structures of the fragment hits in complex with the target, despite efforts by soaking and co-crystallisation. We have done a small crystallographic fragment screen using mutant protein that crystallised more readily and seen some weak covalent binders on the side of the active site. We have however not been able to show further progress with the fragments due to lack of resource, but we have reposited the structures of the fragments to Protein Data Bank and some of the data will be used in future publication on fragment-based methods. |
| Type | Therapeutic Intervention - Cellular and gene therapies |
| Year Development Stage Completed | 2021 |
| Development Status | Under active development/distribution |
| Impact | We use additional funds in the lab to improve some of the fragments and finish the development of a biophysical assay for PH domain membrane binding, and then look for industrial partners for the next stage of the project. There are several companies developing Btk inhibitors and we anticipate that our project will be of interest to these as a backup strategy for their kinase inhibitor programmes. The data in the end was not of sufficient quality, especially given the lack of convincing structural data to take the project forward. We are trying, resources permitting, to evaluate the lysine identified as target for covalent modification for potential for further screening |
| Company Name | Sorex Sensors |
| Description | Sorex Sensors develops very small sensors designed to detect small masses. |
| Year Established | 2017 |
| Impact | Sorex Sensors has now produced a stand-alone box of electronics which connects via USB to a computer and an associated app to drive the box. This allows the sensors to be driven without the need for an expensive Network Analyser and LabVIEW. The company has also transferred production of the sensor devices to a foundry. |
| Website | http://sorexsensors.com |
| Company Name | Cambridge Medical Innovation Ltd |
| Description | |
| Year Established | 2020 |
| Impact | CMI Ltd has been awarded an Innovate UK grant to pilot the technology in NHS Scotland. An NIHR i4i grant application was submitted in December 2020 to cover development and pilot of an integrated platform to enable DigiVis and other digital tests to work within NHS clinician and patient workflows. Cambridge Enterprise has enabled Free of Charge use of DigiVis during the Covid crisis to support remote consultations at CUH and catch up vision screening by CCS. |
| Description | Activity dependent myelination: a mechanism for learning and repair? |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Plenary Lecture - This lecture will cover the progress made in understanding myelination, with a focus on activity-dependent myelination, and explore how the underlying mechanisms of myelin plasticity may underpin myelin regeneration. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Biochemical Society meeting on Small G proteins in cellular signalling and disease |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Small G proteins regulate a plethora of cell signalling pathways thus impacting on most biological processes. As a result of their broad spread cellular influence, the deregulation of these proteins and their pathways often results in disease, especially cancer. The interest, both academic and commercial, in these proteins has always been intense, but with the instigation of the Ras Initiative by the NCI in 2013, interest is newly invigorated. Hopes are high that new ways being developed will successfully target cancers driven by mutant Ras. Topics in this meeting may be invited to submit to our journal, Biochemical Society Transactions, or other publication published by Portland Press, the wholly-owned trading subsidiary of the Biochemical Society. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.eventsforce.net/biochemsoc/frontend/reg/thome.csp?pageID=8162&ef_sel_menu=99&eventID=22 |
| Description | Invited speaker, Microbiology Society (UK) annual meeting 2016 (Ellen Nisbet) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited speaker, Microbiology Society (UK) annual meeting 2016 (Ellen Nisbet) |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://microbiologysociety.org/event/annual-conference/annual-conference-2016.html#tab-4 |
| Description | Neuronal activity dependent myelination and remyelination |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Every other Thursday, VIB-KU LEUVEN CENTER FOR BRAIN & DISEASE RESEARCH invite an international top-scientist to present their work for our research center. During their visit in Leuven, speakers have several one-on-one meetings as well as a lunch with our postdocs and students, to maximize the opportunities for interaction across our entire community. |
| Year(s) Of Engagement Activity | 2019 |
| Description | RSC Emerging Technologies Competition |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | RSC Emerging Technologies Competition: "Artificial metalloproteins for targeted delivery of CO in cancer therapy" |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://www.rsc.org/competitions/emerging-technologies/previous-winners/#2015-winners |
| Description | RadNet Steering Committee meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | RadNet Steering Committee meeting. The study was chosen to present as a collaboration piece for the CRUK RadNet network. The most important impact was to get agreement from all 6 CRUK RadNet centres to join the study. |
| Year(s) Of Engagement Activity | 2020 |
| Description | SBC news article |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Industry/Business |
| Results and Impact | The confidential nature of our data limits further engagement at the moment |
| Year(s) Of Engagement Activity | 2019,2020 |
| Description | Vienna bioscience symposium 2017 (Ellen Nisbet) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presentation at the The Vienna Biocenter (VBC) PhD Programme in Life Sciences |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.training.vbc.ac.at/phd-programme/vbc-student-symposium/invited-speakers-2017/ |