University of Oxford Confidence in Concept Scheme – Round 5

Lead Research Organisation: University of Oxford

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 Participation in P. vivax CHMI workshop
Geographic Reach Asia 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Biotherapeutics Expert Review Panel
Amount £300,000 (GBP)
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2018 
End 03/2021
 
Description Confidence in Concept Award
Amount £72,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 11/2018
 
Description UCSF
Amount £45,000 (GBP)
Organisation University of Oxford 
Department Oxford University Innovation
Sector Private
Country United Kingdom
Start 11/2017 
End 06/2018
 
Title In vitro assay for assessment of antibodies against Plasmodium vivax 
Description We have established at the Jenner Institute an assay to assess the efficacy of antibodies generated by vaccination against Plasmodium vivax malaria. This assay uses a transgenic P. knowlesi malaria parasite adapted to human RBCs, cultured in the presence of polyclonal serum or monoclonal antibodies raised by vaccination with target antigens from P. vivax. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact We are developing new monoclonal antibodies therapeutics for P. vivax malaria and will use this assay to evaluate them. 
 
Title In vitro assays for antimicrobial resistance activity inhibition 
Description We have adapted published methods to measure antimicrobial resistance activity in vitro so that we can show their inhibition with new therapeutics. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact We are developing a new product for antimicrobial resistance and will use this assay to evaluate it 
 
Title PvDBP human mAbs 
Description Human antibodies to PvDBP_RII protein 
Type Of Material Antibody 
Year Produced 2017 
Provided To Others? Yes  
Impact Grants submitted and publication in preparation 
 
Description Angela Russell 
Organisation University of Oxford
Department Department of Pharmacology
Country United Kingdom 
Sector Academic/University 
PI Contribution Structure-based small molecule approach targeting Smoothened, the Hh signal transducer.
Collaborator Contribution The group of Angela Russell will provide small molecules targeting Smoothened, which we will test functionally and, if an effect is observed, will also perform co-crystallisation with Smoothened.
Impact The collaqboration just started.
Start Year 2015
 
Description Dr. Manzano-Prof. Turberfield 
Organisation University of Oxford
Department Department of Physics
Country United Kingdom 
Sector Academic/University 
PI Contribution The Confidence in Concept Scheme - Round 5, MC_PC_16056 project funding allowed me (Dr. Manzano) to build a collaboration with Prof. Turberfield´s team in Physics department (University of Oxford), and particularly with Dr. Antonio García Guerra to design a DNA-based nanoparticle to improve the delivery of oligonucleotides to the CNS. Particularly our team (Dr. Manzano-Prof. Wood) demonstrated the efficacy of delivering LNA-gapmer oligonuclotides to cells obtained from Amyotrophic Lateral Sclerosis patients (ALS)(work published in Brain journal 2017). Limitations in the efficacy of the delivery of these oligoes to motor neurons in vitro prevented this approach to be translated to in vivo models. Our team is currenly validating the ability of DNA-based nanoparticles to increase the delivery of the above mentioned oligoes to motor neurons in ALS patient cells and neuronal cell lines. Moreover, Dr. Manzano has suggested to include a motor neuron specific peptide she has been working on in the past, in these DNA-based nanoparticles to facilitate the uptake by these cells. The future aim will be validating this strategy in vivo in ALS animal models.
Collaborator Contribution Prof. Turberfield´s team has modified DNA-based particles to carry the above mentioned oligoes to neuronal models in vitro. This team has also conjugated the motor neuron specific peptide suggested and provided by Dr. Manzano with the aim of improving the delivery of the oligoes published by Dr. Manzano (Brain 2017) to motor neurons.
Impact The first output of this collaboration is the obtained funding from the CiC program. This is a multi-disciplinary collaboration involving Physics (particle synthesis) and Biological Sciences (use of the synthetic particles to solve a biological need y neuroscience discipline).
Start Year 2017
 
Description Grem1 antibody 
Organisation UCB Pharma
Country United Kingdom 
Sector Private 
PI Contribution We are undertaking preclinical work up of a novel antibody developed by UCB Pharma
Collaborator Contribution Provision of antibody and other reagents, expertise and lab services
Impact pending
Start Year 2016
 
Description Imperial College, London 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Compensation for collaborator's below contributions. Administering and supervising the mosquito challenge.
Collaborator Contribution Accepting mosquitoes from Thailand, checking mosquito infectivity before and after challenge (own microscopists), and providing the facility for performing the mosquito challenge on 2 healthy volunteers
Impact No outputs yet - mosquito challenge planned for April 2018
Start Year 2017
 
Description Mahidol University, Bangkok, Thailand 
Organisation Mahidol University
Country Thailand 
Sector Academic/University 
PI Contribution Intellectual input
Collaborator Contribution Provision of Anopheles mosquitoes for CHMI. Testing of mosquito infectivity and infection clonality. Provision of microscopists to diagnose infection during CHMI study in Oxford (April 2018)
Impact No outputs yet - due April 2018
Start Year 2017
 
Description Michael Jarvis 
Organisation University of Plymouth
Country United Kingdom 
Sector Academic/University 
PI Contribution cloning of constructs for creation of stable cell lines
Collaborator Contribution supplied recombinant CMV vaccine vector expressing Ebola glycoprotein for immunogenicity testing in mice
Impact no outcomes yet, immunogenicity experiments ongoing, cell line creation ongoing
Start Year 2017
 
Description Pharmgenomics - CYP2D6 testing 
Organisation PharmGenomics GmbH
PI Contribution Shipping of clinical blood samples for CYP2D6 genotype testing and compensating PharmGenomics for testing
Collaborator Contribution Testing of clinical blood samples for CYP2D6 genotype testing - in order to predict a healthy trial volunteer's ability to successfully metabolise Primaquine.
Impact To-date 4 volunteers have had blood samples successfully analysed by PharmGenomics. This has contributed to assessment of their eligibility for the VAC068 CHMI P. Vivax study.
Start Year 2017
 
Description Rajat Rohatgi 
Organisation Stanford University
Department School of Medicine
Country United States 
Sector Academic/University 
PI Contribution My laboratory has been engaged in a close and productive collaboration with Rajat Rohatgi's lab at Stanford University over the past two years to understand the structural and mechanistic basis of Smo activation by Shh and by various Smo ligands. Our collaboration on Smoothened has already produced a paper in eLife (2013), which reported the long-sought-after high-resolution crystal structure of the Smo cysteine-rich domain (CRD). I note that the lack of this structure has been a major roadblock in the field; for comparison, the structures of Frizzled CRDs (the closest relatives of the Smo CRD) were reported in 2001. Guided by this structure, the Rohatgi lab used their expertise in Hedgehog signalling assays, oxysterol chemical biology, and microscopy to define, in molecular detail, a hydrophobic groove on the surface of the CRD that binds to oxysterols. This work was made possible by the ideal complement between our expertise in protein engineering/production and crystallography and the Rohatgi lab's development of oxysterol binding assays and a comprehensive panel of Hh signalling assays. We are actively working on crystallizing ligand-bound versions of the CRD and of larger Smo constructs that include both the CRD and the transmembrane (TM) domain. The Rohatgi lab's discovery of a set of CRD ligands that can function as agonists, antagonists and partial agonists are of particular interest since they provide the opportunity to solve structures of Smo in multiple conformational states. In addition, their comprehensive mutagenesis studies to understand the interactions between the CRD and the TM domains will be particularly relevant to our structural approach this same problem.
Collaborator Contribution see above
Impact - Publication in ELIFE (NAchtergaele et al 2013, ELIFE)
Start Year 2011
 
Description Rober Moon 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution Experience with growth inhibition assay for Plasmodium falciparum
Collaborator Contribution Provided transgenic Plasmodium knowlesi for the a growth inhibition assay against Plasmodium vivax
Impact Establishment of the transgenic P. knowlesi growth inhibition assay for the in vitro assessment of the efficacy of vaccines/intervention strategies against P. vivax malaria at the Jenner Institute
Start Year 2018
 
Description Sanger Institute 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Intellectual input and access to data.
Collaborator Contribution Transcriptomics work - both host response and parasite by RNAseq. Genome sequencing of parasite and DNA extraction to test clonality of infection
Impact No outputs yet as samples not to be obtained and analysed until April 2018
Start Year 2017
 
Description University of Edinburgh, UK 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Intellectual input and access to data
Collaborator Contribution Transcriptomics work - both host response and parasite by RNAseq
Impact No outputs yet
Start Year 2017
 
Description WRAIR, USA 
Organisation Walter Reed Army Institute of Research
Country United States 
Sector Public 
PI Contribution Shipping of human plasma samples to WRAIR under appropriate preservation conditions. Compensating WRAIR for the sample analysis.
Collaborator Contribution WRAIR agrees to: •Analyze submitted human plasma samples for levels of primaquine and its metabolite carboxyprimaquine. •Report analyte levels to the study Principal Investigators. •Store samples until study closeout. •Dispose of samples according to relevant protocols.
Impact No outputs yet - clincal samples are to be sent to WRAIR for analysis later this month
Start Year 2018
 
Description XChem screening at Diamond Light Source 
Organisation Diamond Light Source
Country United Kingdom 
Sector Academic/University 
PI Contribution Performed fragment screening at Diamond's XChem facility
Collaborator Contribution Provided access to the XChem facility, including over 30 hours of beamtime at beamline I04-1.
Impact Fragment hits against four different target proteins.
Start Year 2017
 
Description Cafe Scientifique 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Gave a talk on cancer immunotherapy organised by secondary school students aiming for public. 10-20 people, including students and local public attended, and the talk was followed by questions and discussion.
Year(s) Of Engagement Activity 2016,2017
 
Description STEM Networking 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact STEM networking event including STEM ambassadors, Teachers from Oxfordshire Schools and representatives from Abbott Diabetes Care Ltd.
Year(s) Of Engagement Activity 2017
 
Description Women in Science Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Women in Science Day at St Catherine's College in Oxford. Research talk and panel discussion about careers in Science. Approximately 40 sixth form students attended from around the country.
Year(s) Of Engagement Activity 2018