Precision Medicine Exeter Innovation Platform (PMEI Platform): Proof of Concept Funds

Lead Research Organisation: University of Exeter

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

10 25 50
 
Description A pilot study to determine whether novel mitochondria-targeted hydrogen sulfide-antioxidant hybrids can restore cellular bioenergetics in models of mitochondrial disease
Amount £7,516 (GBP)
Organisation Northcott Devon Medical Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2018 
End 12/2018
 
Description Administrative supplement to SEARCH study "use of the T1D-GRS to define diabetes subtype in young people with diabetes"
Amount $112,000 (USD)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start  
 
Description Breakthrough Grant, "Understanding beta-cell destruction through the study of EXtremely Early-Onset Autoimmune Diabetes (EXE-T1D)
Amount $749,000 (USD)
Organisation The Leona M. and Harry B. Helmsley Charitable Trust 
Sector Charity/Non Profit
Country United States
Start  
 
Description Breakthrough initiative grant, "Understanding beta-cell destruction through the study of Extremely Early-Onset Autoimmune Diabetes (EXE-T1D)"
Amount $267,700 (USD)
Organisation The Leona M. and Harry B. Helmsley Charitable Trust 
Sector Charity/Non Profit
Country United States
Start  
 
Description Developing a 'from blood' T1D-GRS biochip
Amount £166,938 (GBP)
Organisation University of Exeter 
Sector Academic/University
Country United Kingdom
Start 02/2020 
End 11/2020
 
Description Developing a long lasting legacy of improved health and educational outcomes stemming from genetic research findings in the Amish
Amount £30,000 (GBP)
Funding ID MRF-145-0003-DG-BAPLE 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 03/2017 
End 03/2018
 
Description Developing a novel genotyping tool to improve diagnosis and clinical management of inherited disease - MRC Confidence in Concept round 3
Amount £137,123 (GBP)
Organisation University of Exeter 
Sector Academic/University
Country United Kingdom
Start 02/2020 
End 02/2021
 
Description Developing a type 1 diabetes genetic risk score to get the right diagnosis and the right treatment for patients with diabetes
Amount £241,113 (GBP)
Funding ID 15/0005297 
Organisation Diabetes UK 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 01/2020
 
Description Diabetes UK PhD Studentship, Prediction of T1D in early life using the T1D GRS, biomarkers, demographics and environmental exposures in a combined risk score.
Amount £101,895 (GBP)
Funding ID 17/0005757 
Organisation Diabetes UK 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Dissemination Award - Development of an online educational resource focussed on the benefits of a community approach to genomic medicine and research
Amount £30,000 (GBP)
Funding ID MRF-145-0005-DG-BAPLE 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 02/2019
 
Description Does mitochondria-targeted hydrogen sulfide prevent and/or reverse cigarette smoke-induced lung injury? Implications for COPD
Amount £965,283 (GBP)
Funding ID MR/S002626/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2018 
End 10/2021
 
Description Epilepsy Foundation Awards: 'Shark Tank' Competition for Innovative Products to Help People Living with Seizures
Amount $5,000 (USD)
Organisation University of Exeter 
Sector Academic/University
Country United Kingdom
Start 05/2017 
End 05/2018
 
Description External Collaboration, Innovation and Entrepreneurism: Translational Medicine in Exeter (EXCITEME)
Amount £17,897 (GBP)
Funding ID MC_PC_16072 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 08/2018
 
Description Harry Keen Fellowship, Career Development award to study Extremely Early onset T1D
Amount £799,000 (GBP)
Organisation Diabetes UK 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Improved, cost effective prediction of type 1 diabetes in early life using combined prediction models
Amount £418,983 (GBP)
Organisation Juvenile Diabetes Research Foundation (JDRF) 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2019 
End 10/2022
 
Description Precision Medicine Exeter Innovation Platform (PMEI Platform)
Amount £44,545 (GBP)
Funding ID MC_PC_15054 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2016 
End 08/2017
 
Description Prediction of T1D in early life (PhD Studentship)
Amount £49,395 (GBP)
Organisation Diabetes UK 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 09/2021
 
Description Promoting Innovation and Collaboration: Translational Medicine in Exeter (PICTME)
Amount £40,000 (GBP)
Funding ID MC_PC_16044 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 02/2019
 
Description Promoting Innovation and Collaboration: Translational Medicine in Exeter (PICTME)
Amount £59,327 (GBP)
Funding ID MC_PC_16044 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 02/2019
 
Description Proof of Concept - Health & Life Sciences - Round 2
Amount £503,848 (GBP)
Funding ID Project ref 103939 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start  
 
Description Reducing inequalities in global healthcare provision through effective research dissemination
Amount £30,000 (GBP)
Funding ID MRF-145-0006-DG-BAPL-C0788 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description University of Exeter, IIB Open Innovation funding platform: AWARDED to J TERRY
Amount £20,166 (GBP)
Organisation Higher Education Funding Council for England 
Sector Public
Country United Kingdom
Start 04/2016 
End 07/2017
 
Description University of Exeter, IIB Open Innovation funding platform: AWARDED to M WHITEMAN
Amount £19,000 (GBP)
Organisation Higher Education Innovation Funding (HEIF) 
Sector Public
Country United Kingdom
Start  
 
Title Genotyping assay - Baple/Crosby - PlexSeq Diagnostics 
Description We have developed an end-to-end, rapid, accurate and cost-effective genotyping assay that may operate via DNA extraction from existing filter paper Guthrie cards taken as part of the existing screening framework for metabolic testing in the US. This has been piloted utilising DNA extracted from filter paper to detect the PCCB gene variant, which has been shown to underlie propionic acidaemia, a common condition in the North American Anabaptist populations which results in poor healthcare outcome for which therapeutic intervention is available if diagnosis is made promptly. We are currently optimising the test parameters and are developing the genotyping assay to enable analysis not only for the PCCB gene variant that underlies this condition, but all of the known founder mutations that have been recognised to underlie inherited diseases occurring within this particular patient group. 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? No  
Impact A notable advantage of the methodology we have utilised for this approach is that it may be readily expanded to increase the number of gene variants (currently several hundred) which may be assayed simultaneously and in parallel on the same DNA sample, through improvements in primer design software. This, together with robotics to increase PCR capacity, will ultimately allow for greater than 100,000 samples to be analysed per day. 
 
Title Improvement of methods - Mike Weedon 
Description • We have successfully set up a pipeline in-house that enables the 10 SNP T1D GRS to be determined using LGC's KASP technology. • We have designed a robotic pipeline that enables 384-well low volume (4ul/reaction) plates to be set-up with minimal hands on time and enables determination of the 10 SNP T1D GRS in up to 28 (previously not genotyped) samples per plate. • Our use of robotics and the QuantStudio 12K Flex Real-time PCR system (ThermoFisher Scientific) for thermocycling and fluorescence analysis means we observe, with respect to the fluorescence values for the KASP genotyping assays, very low inter-plate variability. This is enabling us to explore the possibility of using these assays to determine the 10 SNP T1D GRS in Diagnostic samples and replace the expensive Sanger sequencing method which is currently used. • We have validated our T1D GRS genotyping results for KASP by comparing with Sanger sequencing calls. We have genotyped by KASP 308 samples with T1D GRS previously determined by Sanger. 3032/3080 (98.4%) reactions were assigned a genotype and 3029/3032 (99.9%) genotypes consistent with Sanger calls. • To avoid calculating incorrect T1D GRSs our comparison of genotypes determined by KASP and Sanger has led directly to the re-design of PCR primers for the Diagnostic Sanger assay. • We have collaborated with Randox, a market leader in the Diagnostics industry, who are developing a PCR-based microchip to determine the 10 SNP T1D GRS. We have compared genotyping results determined by their technology and by KASP assays. These analyses have led to the re-design of primers used in their assay, an assay which is likely to be used to help diagnose people with diabetes worldwide. • We have used the KASP assays to determine the T1D GRS in FFPE DNA samples from a large collection of autopsy pancreas samples taken from individuals newly diagnosed with type 1 diabetes. Knowledge of the T1D GRS for these individuals is of much interest to the field, potentially enabling novel associations between genetic and cellular markers of the disease to be uncovered. The low quantity and degraded nature of FFPE samples meant the KASP assays could determine the T1D GRS where sequencing technologies (Sanger and NGS) had failed. 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? No  
Impact N/A 
 
Title Ohio Amish community sequencing data 
Description Population specific database of aggregated whole exome sequencing data has been developed for the Ohio Amish community 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Still active 
 
Description Bringing a Type 1 diabetes genetic risk score into the clinic for better diabetes diagnosis 
Organisation Randox Laboratories
Country Global 
Sector Private 
PI Contribution Preliminary meetings with Randox have taken place to outline a potential project and collaboration. UoE have provided Randox with samples as a test of the assay validity. The aim is to provide Randox with the statistical model which will incorporate genetic information with clinical and other biomarker information to give a highly predictive Type 1 diabetes probability.
Collaborator Contribution Randox have developed a version of their array technology for the genetic variants that are required for performing the Type 1 diabetes genetic risk score. Randox have genotyped samples provided by and error rates were < 0.05%. They are working on improving the accuracy of the test further.
Impact Outcomes are pending; the plan is to have a genotyping product which can be situated in clinical chemistry so that clinicians can get a genetic test at diagnosis of diabetes to ensure accurate diagnosis. The test will incorporate genetic, clinical and any biomarker data (e.g. antibodies or c-peptide) to provide an accurate probability of diabetes subtype. The potential impact of this product will be on patients who will get the correct diagnosis of diabetes. Given that 15% of young (20-50yr) adults have their diabetes misdiagnosed this is a lot of individuals who are, for example, taking insulin needlessly. This will also impact the NHS finances by ensuring only people that require insulin are on insulin and that the correct treatment is provided so that diabetes is better controlled and diabetes-associated diseases are less common and cost the NHS less.
Start Year 2016
 
Description The development of a community specific newborn screening programme for the North American Anabaptist communities 
Organisation PlexSeq Diagnostics
Country United States 
Sector Private 
PI Contribution Dr E Baple and her research team will develop a novel methodology for the extraction of DNA from filter paper and then, alongside industry partners, develop a high throughput and accurate genetic-based population-specific newborn screening programme.
Collaborator Contribution The industry partner - PlexSeq Diagnostics - will provide consumable and machine running costs for the development of the genetic sequencing assay at an estimated in-kind cost of £40,000.
Impact Outputs pending - preliminary stages commenced in December of 2016. The Collaboration Agreement with PlexSeq Diagnostics is pending final signature.
Start Year 2016
 
Title ASSESSING SUSCEPTIBILITY TO EPILEPSY AND EPILEPTIC SEIZURES 
Description Assessing Susceptibility to Epilepsy and Epileptic Seizures A method and system adapted to assist with assessing susceptibility to epilepsy and/or epileptic seizures in a patient receives (202) patient brain data and generates (204) a network model from the received patient brain data. The system further generates (206) synthetic brain activity data in at least some of the nodes of the network model and computes (208) seizure frequency from the synthetic brain activity data by monitoring transitions from non-seizure states to seizures states in at least some of the nodes over time. The system further includes a device (104, 110) configured to use the seizure frequency to compute (210) a likelihood of susceptibility to epilepsy and/or epileptic seizures in the patient, and a device (104, 110) configured to compare (212) the computed likelihood with another likelihood of susceptibility to epilepsy and/or epileptic seizures in order to assess whether the likelihood has increased or decreased. Fig. 2 
IP Reference WO2013182848 
Protection Patent application published
Year Protection Granted 2013
Licensed No
Impact We are in the early stages of forming a spin-out company, in collaboration with the King's College IP and Licencing team, following the results of our health economic assessment quantifying the economic potential of our technology.
 
Title HYDROGEN SULFIDE RELEASING COMPOUNDS AND THEIR USE 
Description The invention relates to a compound comprising a mitochondrial targeting group linked to group capable of releasing hydrogen sulfide, or a pharmaceutically acceptable salt thereof, for use in the treatment of the human or animal body by surgery or therapy. The invention also relates to the use of the compound in the treatment of a plant, and to certain forms of the compound. 
IP Reference WO2013045951 
Protection Patent application published
Year Protection Granted 2013
Licensed No
Impact None at this point
 
Title Prof. Matt Whiteman - Mitochondrial targeted H2S donor compounds toxicology 
Description • This project aimed to carry out toxicological evaluation of a panel of mitochondrial-targeted H2S donors, three in vitro tests have been carried out: • 1- hERG Channel Screen - result has been obtained and reported. Further testing is required. • 2- Micronucleus test (replacing Cytochrome P450 Inhibition Screen on advice) - Cytochrome P450 Inhibition Screen to be carried out latterly. • 3- Bacterial Reverse Mutation Test - all three compounds are not mutagenic (AP39, AP1231, RT01). • The findings have been summarised in a confidential report. Most recent source of funding for this came from Precision Medicine Exeter Innovation Platform (PMEI Platform): Proof of Concept Funds. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2017
Development Status Under active development/distribution
Impact Prof Whiteman has established pre-clinical in vivo efficacy in the following areas (most published) (i) COPD and smoke-induced emphysema, (ii) neuroprotection after cardiac arrest, (iii) myocardial infarction including reversal of MI-induced arrhythmias, (iv) organ transplantation (including in pigs), (iv) blunt chest- / blast wave-induced trauma with haemorrhagic shock, (iv) burn injury, (v) AKI, (vi) diabetic retinopathy and nephropathy, (vii) hypertension, (viii) cardiovascular ageing (ix)muscular dystrophy and sarcopenia, (x) Alzheimer's disease etc. 
 
Company Name Neuronostics 
Description Neuronostics, founded by Prof John Terry, has developed patient-specific software (BioEP) for epilepsy diagnosis decision support. BioEP analyses short segments of an individual's resting state neurological electrical activity to provide accurate, objective and real-time assessments of a person's likelihood of suffering epilepsy and seizures. Neuronostics promises to revolutionise the epilepsy care pathway through reducing diagnostic uncertainty and enhancing cost-effectiveness in healthcare. 
Year Established 2017 
Impact Company founded 22nd December 2017. Notable impacts TBC.
 
Description Akron Children's Hospital Grand Round 
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 Akron Children's Hospital Grand Round focused on the diagnosis of inherited diseases in the Amish community - "Think Global, Practice Local: Community Genetics in Amish Country", 9 March 2018.
Year(s) Of Engagement Activity 2018
URL https://cmetracker.net/CHMCA/Catalog
 
Description American Diabetes Association Scientific sessions Invited lecture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact American Diabetes Association Scientific sessions Invited lecture: "Beyond Single Nucleotide Polymorphisms?Building on Knowledge of the Genetic Architecture of Diabetes"
Year(s) Of Engagement Activity 2018
 
Description BBC Radio 4 Inside Science 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Dr Baple and Prof Crosby were featured on BBC Inside Science (BBC Radio 4), "Genetic diseases in Amish communities" discussing their Windows of Hope project with Anabaptist communities in North America.
Year(s) Of Engagement Activity 2020
URL https://www.bbc.co.uk/programmes/m000dgbt
 
Description Engagement with primary care providers in Anabaptist populations - Midwife engagement conference 
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 We have engaged with primary care providers and midwives who serve the Anabaptist populations to determine the practicalities of introducing related test methodologies targeted at specific patient groups. This is a vital step in establishing proof of principle data to enable marketing new approaches for testing to healthcare companies in order to provide services to other patient groups in which this would be a commercially viable option.
Year(s) Of Engagement Activity 2017
 
Description Immunology of Diabetes Society Invited lecture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Immunology of Diabetes Society Congress 2018, London
Session 9: Big Data - ""The use of Big data in T1D research"
Fleming, 3rd Floor, QEII Centre 27 Oct 2018 13:30 - 15:00
Year(s) Of Engagement Activity 2018
URL https://ids2018.org/en/program-schedule/program/23/session-9-big-data
 
Description News article for Milwaukee Journal Sentinel 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact News article with Pulitzer prize winning journalist Mark Johnson for Milwaukee Journal Sentinel, also picked up by USA today and Apple news, most read article over Thanksgiving in 2019
Year(s) Of Engagement Activity 2019
URL https://www.pressreader.com/usa/milwaukee-journal-sentinel/20191014/282033328958468
 
Description Oxford Centre for Diabetes and Metabolism, University of Oxford, Invited lecture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Oxford Centre for Diabetes and Metabolism (OCDEM), University of Oxford, "Clinical and research uses of Genetic risk scores in common disease"
Date: 16 May 2018, 13:00 (Wednesday, 4th week, Trinity 2018)
Venue: Robert Turner Lecture Theatre
Organising department: Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM)
Part of: OCDEM Wednesday Seminar Series
Year(s) Of Engagement Activity 2018
URL https://talks.ox.ac.uk/talks/id/2ccad19c-2f6a-49d6-b093-5d07b3753086/
 
Description Platform presentation (accepted abstract) describing the development of the genotyping assay - Elizabeth Town "Health and Well-Being in Amish Society" conference June 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact This conference will focus on health, healing, health care, and individual and community welfare and well-being in Amish life. Since at least 1964, with the publication of the essay "Genetic Studies of the Amish," by Victor McKusick, John Hostetler, and Janice Egeland, scholars have identified the unique contribution that Amish communities play in advancing medical knowledge. In the years since then, clinical studies, ethnographic research, and creative new avenues for providing health care have flourished with the active participation of the Amish.
Year(s) Of Engagement Activity 2019
URL https://www.etown.edu/centers/young-center/amish-conference2019.aspx
 
Description Translational Medicine in plain populations conference, University of Wisconsin, 2018 
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 This two-day event focuses on the clinical care and research of genetic conditions that affect the Plain Community, including Old Order Amish and Mennonites. The conference highlights novel research and therapies for rare genetic conditions and collaborative efforts between major medical centers, universities and a consortium of rural health clinics. The conference brings together clinicians, scientists, midwives, administrators, and Plain community members to discuss relevant health and scientific topics.
Year(s) Of Engagement Activity 2018
URL https://www.waisman.wisc.edu/event/plain-conference-2018/
 
Description University of Chicago, USA, Kovler Diabetes Centre Special Seminar 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact University of Chicago, USA, Kovler Diabetes Centre Special Seminar "Type 1 Diabetes Genetic Risk Scores"
Year(s) Of Engagement Activity 2017
 
Description University of Indiana, USA, Special Seminar 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact University of Indiana, USA Special Seminar "Genetics of Type 1 Diabetes"
Year(s) Of Engagement Activity 2017