Promoting Innovation and Collaboration: Translational Medicine in Exeter (PICTME)

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

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Islinger M (2018) The peroxisome: an update on mysteries 2.0. in Histochemistry and cell biology

 
Description Marie Sklodowska-Curie Actions, Innovative Training Networks (ITN) (PERICO)
Amount € 3,900,000 (EUR)
Funding ID 812968 
Organisation European Commission 
Department Horizon 2020
Sector Public
Country European Union (EU)
Start  
 
Description Molecules & Cells Sciences Committee
Amount £592,000 (GBP)
Funding ID BB/R016844/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2018 
End 11/2021
 
Title Reporter cell line 
Description Reporter cell lin efor screening of ACBD5 expression 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? No  
Impact
 
Description Modulation of ACBD5 to reduce lipid accumulation in X-linked adrenoleukodystophy and related disorders 
Organisation Academic Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution We have an existing relationship with the AMC/Prof. Hans R. Waterham. We recently published cooperative research on ACBD5 deficiency, a novel peroxisomal disorder, which was diagnosed and characterised in a cooperative approach (Ferdinandusse et al. 2017, J Med Genet. 54:330). The findings are relevant for this application. Prof. Waterham's research is focused on the molecular biology and clinical genetics of metabolic disorders with particular emphasis on peroxisomal defects. He made significant contributions to the classification, discovery and diagnostics of peroxisomal disorders (Wanders & Waterham 2006, Annu Rev Biochem 75:295; Waterham et al. 2007, N Engl J Med 356:1736; Ebberink et al. 2011, Hum Mutat 32:59) and established innovative tools and models to measure peroxisomal lipid metabolism (van Roermund et al. 2008, FASEB J 22:4201). In addition, we have established a relationship with Novartis Institutes for BioMedical Research, Basel, Switzerland. Novartis will provide access to screening technologies/facilities and support a cell-based screen with up to 50'000 compounds. All data, along with structures of confirmed active compounds will be freely shared with M. Schrader and the University of Exeter. Based on the legal framework of a standard collaboration agreement, M. Schrader/UoE will keep all IP.
Collaborator Contribution The Academic Medical Centre/Prof. H. Waterham will make an "in kind" contribution. They will support the generation of yeast strains and lipid/ß-oxidation measurements and cover costs for consumables/reagents (£8,000) as well as salary costs of a research technician (0.5 FTE for two months) (£2,427) for yeast work and mammalian cell culture at AMC. As an "in-kind" contribution, Novartis will contribute up to 50'000 LC/MS quality-controlled compounds in enough quantity to screen up to 10 µM final concentration; 1536/384 microtiter plates suitable for the screen and calibrated for the Novartis screening instruments; Robotic tips, liquid dispenser cassettes and other consumables for the screen; Tissue culture vessels and medium for culturing and expansion of the reporter cell line; Functional, up-to data screening infrastructure and data capturing/processing/management pipelines; Support with processing of the raw data by Novartis bioinformaticians. We estimated a match funding of £25,000 (the contribution will likely be higher).
Impact TBC
Start Year 2017
 
Description Modulation of ACBD5 to reduce lipid accumulation in X-linked adrenoleukodystophy and related disorders 
Organisation Novartis
Country Global 
Sector Private 
PI Contribution We have an existing relationship with the AMC/Prof. Hans R. Waterham. We recently published cooperative research on ACBD5 deficiency, a novel peroxisomal disorder, which was diagnosed and characterised in a cooperative approach (Ferdinandusse et al. 2017, J Med Genet. 54:330). The findings are relevant for this application. Prof. Waterham's research is focused on the molecular biology and clinical genetics of metabolic disorders with particular emphasis on peroxisomal defects. He made significant contributions to the classification, discovery and diagnostics of peroxisomal disorders (Wanders & Waterham 2006, Annu Rev Biochem 75:295; Waterham et al. 2007, N Engl J Med 356:1736; Ebberink et al. 2011, Hum Mutat 32:59) and established innovative tools and models to measure peroxisomal lipid metabolism (van Roermund et al. 2008, FASEB J 22:4201). In addition, we have established a relationship with Novartis Institutes for BioMedical Research, Basel, Switzerland. Novartis will provide access to screening technologies/facilities and support a cell-based screen with up to 50'000 compounds. All data, along with structures of confirmed active compounds will be freely shared with M. Schrader and the University of Exeter. Based on the legal framework of a standard collaboration agreement, M. Schrader/UoE will keep all IP.
Collaborator Contribution The Academic Medical Centre/Prof. H. Waterham will make an "in kind" contribution. They will support the generation of yeast strains and lipid/ß-oxidation measurements and cover costs for consumables/reagents (£8,000) as well as salary costs of a research technician (0.5 FTE for two months) (£2,427) for yeast work and mammalian cell culture at AMC. As an "in-kind" contribution, Novartis will contribute up to 50'000 LC/MS quality-controlled compounds in enough quantity to screen up to 10 µM final concentration; 1536/384 microtiter plates suitable for the screen and calibrated for the Novartis screening instruments; Robotic tips, liquid dispenser cassettes and other consumables for the screen; Tissue culture vessels and medium for culturing and expansion of the reporter cell line; Functional, up-to data screening infrastructure and data capturing/processing/management pipelines; Support with processing of the raw data by Novartis bioinformaticians. We estimated a match funding of £25,000 (the contribution will likely be higher).
Impact TBC
Start Year 2017
 
Description Project manager for completion of regulatory documentation for a phase 1 trial of neural stem therapy for Alzheimer's disease 
Organisation Reneuron
Country United Kingdom 
Sector Private 
PI Contribution Past studies with stem cell transplantation in animal models of Alzheimer's disease have shown positive outcomes, indicating that this may be linked to the stimulation of factors in the brain that promote cell regeneration. However, to date no human grade stem cells have been available to test the efficacy of this treatment in people with Alzheimer's disease. There is now an exciting opportunity to take forward a human grade neural stem line (the CTX line) into a clinical trial, but the university first needs expert support to overcome regulatory hurdles so that this can be approved.This collaboration with ReNeuron seeks to initiate a 'first in man' clinical trial of Neural Stem Cell implantation for those with early Alzheimer's disease. This ground-breaking study could lead to the development of a major disease modifying therapy for dementia, a condition affecting over 850,000 people in the UK. Alzheimer's disease accounts for the majority of people with dementia (50-70%) and there are currently no effective disease modifying treatments; hence a huge unmet need.
Collaborator Contribution ReNeuron is a strategic partner providing the cells, background IP and human safety data. If successful this project will likely lead to a joint venture with the company, and could represent a natural extension to their future pipeline depending on the successful outcome of their current trial on stroke. Stem-cell therapy in the form of bone marrow transplant is now widely accepted as a therapy. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions. Companies belonging to this business sector would likely find the spin-out an attractive option for a potential acquisition. £180k in-kind contribution from ReNeuron in the form of stem cells (£160k) and consultancy (£20k). Dr Joe Butchart- Consultant in Geriatric Medicine (RD&E) and Professor Dag Aarsland and Professor Ashkan Keyoumars from Kings College will be key clinician and clinic advisors.
Impact TBC
Start Year 2017
 
Description Toward finding novel diagnostic solutions for children with celiac disease, using common genetic variation 
Organisation Randox Laboratories
Country Global 
Sector Private 
PI Contribution Confidence in Concept funding: We are requesting a full time E28 post-doc with laboratory and bioinformatics skills for 9 months. Working with the principal applicant, their time will predominantly be taken up with 1. Development of in house LGC and taqman genotyping assays, data handling and analysis tasks, including storing, manipulating and statistically analysing the genome-wide association study from the UK Biobank, and statistically refining and assessing the genetic risk score. In addition to informatic skills, the applicant will also be involved in developing the in house assay which requires some basic wet-lab laboratory experience. Consumables: We have budgeted for the development of 70 KASP genotyping assays to be genotyped in a maximum of 2500 samples to allow for development of the tests. See below section for consumable costings. UoE College of Medicine and Health will cover directly allocated costs for staff involved (estates, indirect, salary costs for PI and CoI @ 2 hrs/week, and JL 9 months FTE) and overheads.
Collaborator Contribution RANDOX will provide (in-kind): - Full time salary for 1 Research Scientist to optimise Celiac disease related primers on biochip Assay, complete verification on samples provided by Exeter and complete necessary verification and validation studies for CE Marking of product. - Salary costs for Randox staff. Salary costs for software analyst to integrate risk Score into Randox Investigator current software. - Production of Biochips for development, verification and validation of Celiac related primers on Biochip Assay. 3 lots of reagents are required for such studies. Travel to University of Exeter for Randox staff
Impact Still active
Start Year 2018
 
Description 2nd EMBO Workshop on Membrane Contact Sites 
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 2nd EMBO Workshop on Membrane Contact Sites, Arosa, Switzerland (September 21 - 25, 2018): "Peroxisome-organelle contacts in mammals - implications for health and disease" (invited speaker)
Year(s) Of Engagement Activity 2018
URL http://meetings.embo.org/event/18-membrane
 
Description Spalding Gentlemen's Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Spalding Gentlemen's Society, Spalding, UK (November 16, 2018): "The cell biology of disease - how faulty "factories" in the cell can make us sick"
Year(s) Of Engagement Activity 2018
URL https://www.sgsoc.org/lectures