Tropical Infectious Disease Consortium: Sustaining, Expanding and Accelerating Product Development
Lead Research Organisation:
Liverpool School of Tropical Medicine
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.
Organisations
- Liverpool School of Tropical Medicine (Lead Research Organisation)
- The Clatterbridge Cancer Centre NHS Foundation Trust (Collaboration)
- Kirkstall Ltd (Collaboration)
- Medicines for Malaria Venture (MMV) (Collaboration)
- QIAGEN (Collaboration)
- Pharmidex (Collaboration)
- Vaccitech Ltd (Collaboration)
- Xeroshield (Collaboration)
- M.C.I Animal Health (Collaboration)
- Pfizer Inc (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- Smith College (Collaboration)
- PUBLIC HEALTH ENGLAND (Collaboration)
- Redx Pharma Plc (Collaboration)
- Kalinga Institute of Industrial Technology (KIIT) University (Collaboration)
- Avacta Group (Collaboration)
- Salvensis (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- Butantan Institute (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- Bayer (Collaboration)
- Vellore Institute of Technology University (Collaboration)
- IVCC (Collaboration)
- National Institute of Allergy and Infectious Diseases (NIAID) (Collaboration)
- ALDER HEY CHILDREN'S NHS FOUNDATION TRUST (Collaboration)
- London School of Hygiene and Tropical Medicine (LSHTM) (Collaboration)
- Invitrocue (Collaboration)
- Epistem (Collaboration)
- Godrej Group (Collaboration)
- AMR Centre (Collaboration)
- Blueberry Therapeutics (Collaboration)
People |
ORCID iD |
Stephen Ward (Principal Investigator) |
Publications
Ismail H
(2016)
A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile
in Angewandte Chemie International Edition
Ismail HM
(2016)
Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7.
in Proceedings of the National Academy of Sciences of the United States of America
Ismail HM
(2016)
Corrigendum: A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.
in Angewandte Chemie (International ed. in English)
Ismail HM
(2016)
A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.
in Angewandte Chemie (Weinheim an der Bergstrasse, Germany)
Jin C
(2019)
Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model.
in PLoS neglected tropical diseases
Kaewpruk N
(2016)
PFMDR1 POLYMORPHISMS INFLUENCE ON IN VITRO SENSITIVITY OF THAI PLASMODIUM FALCIPARUM ISOLATES TO PRIMAQUINE, SITAMAQUINE AND TAFENOQUINE.
in The Southeast Asian journal of tropical medicine and public health
McConville M
(2015)
Carbamoyl Triazoles, Known Serine Protease Inhibitors, Are a Potent New Class of Antimalarials.
in Journal of medicinal chemistry
Mungthin M
(2017)
Influence of the pfmdr1 Gene on In Vitro Sensitivities of Piperaquine in Thai Isolates of Plasmodium falciparum.
in The American journal of tropical medicine and hygiene
Munster VJ
(2017)
Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model.
in NPJ vaccines
Description | External Scientific Advisory Board Member for the German Centre for Infection Research |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Macrofilaricide Drug Accelerator (MacDA) 2015 to date |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Description | Membership of the Structure-guided Drug Discovery Coalition |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | • UK management committee member for COST Action CM1307, 'Targeted chemotherapy towards diseases caused by endoparasites" - 2014- to date |
Geographic Reach | Europe |
Policy Influence Type | Influenced training of practitioners or researchers |
URL | http://www.costcm1307.org/CM1307/Home.html |
Description | Alder Hey Children's Charity |
Amount | £9,791 (GBP) |
Organisation | Alder Hey Children's NHS Foundation Trust |
Sector | Public |
Country | United Kingdom |
Start | 12/2017 |
End | 06/2018 |
Description | An antimalarial drug targeting Plasmodium phosphodiesterases to cure patients and block transmission; a new tool to combat drug resistance |
Amount | £95,216 (GBP) |
Funding ID | BSA35 |
Organisation | United Kingdom Research and Innovation |
Department | The Bloomsbury SET |
Sector | Public |
Country | United Kingdom |
Start | 03/2020 |
End | 01/2021 |
Description | Co-funding from Industry |
Amount | £70,000 (GBP) |
Organisation | Vaccitech Ltd |
Sector | Private |
Country | United Kingdom |
Start | 11/2016 |
End | 06/2017 |
Description | Confidence in Concept (CiC) by MRC |
Amount | £46,750 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2015 |
End | 03/2017 |
Description | Contribution towards assessment of rapid and safe diagnostic assays for Lassa Fever in |
Amount | £49,000 (GBP) |
Funding ID | ZK/16-025 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2019 |
Description | Exapnding Excellence in England 'Centre for Drugs and Diagnostics' |
Amount | £9,843,478 (GBP) |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 07/2024 |
End | 07/2029 |
Description | Expanding Excellence |
Amount | £9,843,478 (GBP) |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 07/2024 |
End | 07/2029 |
Description | Functional analysis of the downstream mediators of cyclic nucleotide signalling in malaria parasites |
Amount | £1,358,884 (GBP) |
Funding ID | 220318/Z/20/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2020 |
End | 06/2024 |
Description | Global Challenges Research Fund |
Amount | £502,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2017 |
End | 04/2019 |
Description | Grand Challenge Explorations Phase II |
Amount | $424,874 (USD) |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 02/2017 |
End | 02/2019 |
Description | Impact Acceleration Accounts (IAA) Scheme ' Tropical Infectious Disease Consortium: Expanding and Accelerating Product Development |
Amount | £306,774 (GBP) |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 03/2023 |
End | 03/2025 |
Description | Innovator Award |
Amount | £500,000 (GBP) |
Funding ID | 223849/Z/21/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2022 |
End | 01/2024 |
Description | Institutional Partnership Awards 'LSTM translational enabler' |
Amount | £300,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2022 |
End | 03/2023 |
Description | Institutional Partnership Awards 'LSTM translational enabler' |
Amount | £300,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2022 |
End | 03/2023 |
Description | Intensive Care Society New Investigator Award |
Amount | £10,791 (GBP) |
Funding ID | SU9AGB |
Organisation | Intensive Care Foundation (ICF) |
Sector | Private |
Country | Australia |
Start | 06/2017 |
End | 07/2018 |
Description | Lead optimisation of a series of antimalarial plasmepsin IX/X beta-hydroxyethylamine based inhibitors |
Amount | £1,300,000 (GBP) |
Funding ID | MR/Y008774/1 |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 02/2024 |
End | 01/2026 |
Description | MICA: Defining the two step relay mechanism of action of the 8-aminoquinolines. A precondition for optimal combination therapies for relapse malaria |
Amount | £642,413 (GBP) |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2024 |
Description | MICA: Defining the two-step relay mechanism of action of the 8 amino-quinolines: A precondition for optimal combination therapies for relapse malaria |
Amount | £642,413 (GBP) |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2024 |
Description | MRC |
Amount | £500,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Department | MRC Confidence in Concept Scheme |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2015 |
End | 08/2016 |
Description | MRC Biomedical Catalyst DPFS'Lead Optimisation of a series of antimalarial plasmepsin IX/X beta-hydroxyethylamine based inhibitors |
Amount | £1,300,000 (GBP) |
Funding ID | MR/Y008774/1 |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 02/2024 |
End | 01/2026 |
Description | MRC Confidence in Concept Scheme |
Amount | £45,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2015 |
End | 02/2016 |
Description | MRC Studentship |
Amount | £50,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2016 |
End | 07/2019 |
Description | MRC Translational and Quantitative Skills Doctoral Training Programme in Global Health |
Amount | £500,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2025 |
Description | New 4-aminoquinolines against drug resistant malaria and coronaviruses |
Amount | $108,586 (USD) |
Organisation | Medicines for Malaria Venture (MMV) |
Sector | Charity/Non Profit |
Country | Switzerland |
Start | 03/2020 |
End | 03/2021 |
Description | Optimisation of malaria parasite phosphodiesterase expression for studies to support structure-based drug design |
Amount | £19,830 (GBP) |
Funding ID | 214227/Z/18/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2020 |
End | 02/2021 |
Description | Optimisation of phosphodiesterase inhibitors to provide in vivo proof of concept for development of a new antimalarial drug |
Amount | £503,907 (GBP) |
Funding ID | 209367/Z/17/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2019 |
End | 01/2021 |
Description | Research England Connecting Capability Fund: Bloomsbury SET Impact Connector Consortium |
Amount | £1,900,000 (GBP) |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2022 |
Description | Translational Development Fund |
Amount | £2,700,000 (GBP) |
Organisation | LifeArc |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2023 |
End | 03/2025 |
Description | Translational and Quantitative Skills Doctoral Training Programme in Global Health |
Amount | £1,950,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2028 |
Description | UK Vaccine Network |
Amount | £1,866,981 (GBP) |
Funding ID | R45331/CN001 |
Organisation | Department of Health Social Services and Public Safety (DHSSPS) |
Sector | Public |
Country | United Kingdom |
Start | 08/2016 |
End | 08/2019 |
Description | UKRI MRC Impact Acceleration Accounts (IAA) Scheme 'Tropical Infectious Disease Consortium: Expanding and Accelerating Product Development |
Amount | £306,774 (GBP) |
Organisation | United Kingdom Research and Innovation |
Sector | Public |
Country | United Kingdom |
Start | 03/2023 |
End | 03/2026 |
Title | Genedrive kdr probes |
Description | Probes for detecting resistance mutations in pyrethroid target (kdr) |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | Still being validated |
Title | Whole blood phagocytosis assay |
Description | We developed this assay to measure neutrophil function in whole blood. This was initially done to measure the effect of P4 peptide on phagocytic function but has since be utilised by multiple different partners to measure neutrophil function in a variety of different ways (including neutrophil function after chemotherapy, neutrophil function in response to histone toxins and neutrophil function in paediatric patients) |
Type Of Material | Biological samples |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | Through this method we have established multiple partnerships with institutions at UoL, Alder Hey, Malawi Liverpool-Wellcome Trust Clinical Research Centre and Cambridge. These collaborations all have active research projects using the assay that will should come to fruition in the form of published manuscripts in the next couple of years. |
Title | OptiMal-PK: an internet-based, user-friendly interface for the mathematical-based design of optimized anti-malarial treatment regimens |
Description | Background The search for highly effective anti-malarial therapies has gathered pace and recent years have seen a number of promising single and combined therapies reach the late stages of development. A key drug development challenge is the need for early assessment of the clinical utility of new drug leads as it is often unclear for developers whether efforts should be focused on efficacy or metabolic stability/exposure or indeed whether the continuation of iterative QSAR (quantitative structure-activity and relationships) cycles of medicinal chemistry and biological testing will translate to improved clinical efficacy. Pharmacokinetic and pharmacodynamic (PK/PD)-based measurements available from in vitro studies can be used for such clinical predictions. However, these predictions often require bespoke mathematical PK/PD modelling expertise and are normally performed after candidate development and, therefore, not during the pre-clinical development phase when such decisions need to be made. Methods An internet-based tool has been developed using STELLA® software. The tool simulates multiple differential equations that describe anti-malarial PK/PD relationships where the user can easily input PK/PD parameters. The tool utilizes a simple stop-light system to indicate the efficacy of each combination of parameters. This tool, called OptiMal-PK, additionally allows for the investigation of the effect of drug combinations with known or custom compounds. Results The results of simulations obtained from OptiMal-PK were compared to a previously published and validated mathematical model on which this tool is based. The tool has also been used to simulate the PK/PD relationship for a number of existing anti-malarial drugs in single or combined treatment. Simulations were predictive of the published clinical parasitological clearance activities for these existing therapies. Conclusions OptiMal-PK is designed to be implemented by medicinal chemists and pharmacologists during the pre-clinical anti-malarial drug development phase to explore the impact of different PK/PD parameters upon the predicted clinical activity of any new compound. It can help investigators to identify which pharmacological features of a compound are most important to the clinical performance of a new chemical entity and how partner drugs could potentially improve the activity of existing therapies. |
Type Of Material | Computer model/algorithm |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | The software has been used by a number of users for both teaching and research purposes. The use of the model has lowered the number of animal experiments in my laboratory but it is difficult to estimate how many in vivo experiments it has reduced externally. We are currently working to promote the on-line tool. |
URL | http://optimalpk.lstmed.ac.uk |
Title | prospective evaluations of novel RT-PCR assays for the diagnosis of dengue and chikungunya |
Description | We have conducted prospective evaluations of novel RT-PCR assays for the diagnosis of dengue and chikungunya in Ecuador, Guatemala and Brazil. The new assays were compared to the reference standard in the national surveillance laboratories (the CDC assays for these viruses). |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | We are currently conducting sequencing of selected samples to confirm our findings. Pending final confirmation, the assays developed (by LSTM in collaboration with Qiagen) are as sensitive and specific as the reference standard |
Description | 3D Macrophage infection and Drug studies |
Organisation | Invitrocue |
Country | Singapore |
Sector | Private |
PI Contribution | I have conducted 3D culture of different macrophage and fibroblast types within the INVITROCUE Cellulosponge scaffold. I have established an infection model for Leishmaniasis in 3D cultured macrophages and have tested standards drugs against these 3D infected macrophages. Analysis of samples has been conducted using fluorescent parasites and confocal imaging |
Collaborator Contribution | INVITROCUE has provided cellulosponges at a reduced price and have provided support on the use of the scaffold. They have also aided in the computational analysis of the image of drug treated macrophages produced using the confocal microscope. |
Impact | Comparison of the drug treatment of leishmania infected macrophages in 2D and 3D have been analysed and compared. The computational analysis has provided a quick and easy source of results for the assay. Experiments have been conducted but analysis is still in progress. |
Start Year | 2014 |
Description | AMR Centre |
Organisation | AMR Centre |
Country | United Kingdom |
Sector | Public |
PI Contribution | We are currently in discussion on industrial partnership to take P4 peptide forward to FIH studies. |
Collaborator Contribution | Currently in negotiation under NDA |
Impact | Nil yet |
Start Year | 2019 |
Description | Alder Hey Collaboration |
Organisation | Alder Hey Children's NHS Foundation Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | We processed blood samples taken from children admitted to PICU with sepsis and healthy child volunteers (blood sample taken under general anaesthetic for routine surgery). We have used our innovative assay that requires less than 2ml blood to measure neutrophil function with and without the immunostimulatory drug P4 peptide. We have processed and saved excess plasma in order to facilitate further analysis. We provided the clinical protocols and platform for the study based on our adult study used to validate the assay that we refined during the course of the award. We made available our CRN Portfolio sponsorship gained through funding of the study in order to facilitate research nurse screening and recruitment if patients. |
Collaborator Contribution | Alder Hey wrote the ethical amendment and child information / parental consent forms for the study. Subsequently Alder Hey have screened, consented and took blod form children before transporting it to LSTM for analysis. Following on from this project we have developed closer collaboration with clinician/academics at Alder Hey and now plan to use the assay developed during this award to measure neutrophil function before and after chemotherapy in children with cancer. The question we seek to address here is whether we can predict which patients will go on to develop neutropenic fever/sepsis. |
Impact | We completed recruitment to this study in April2017 - we are now in the process of wirting a manuscript for submission. |
Start Year | 2015 |
Description | Avacta |
Organisation | Avacta Group |
Country | United Kingdom |
Sector | Private |
PI Contribution | Contacts made following Adhiron CiC project and meeting held in Leeds for networking Adhiron technology. Avacta have interests in venoms,thus connections made with Dr Harrison and Venom Research Unit to develop reserach project |
Collaborator Contribution | Avacta are preparing MOU and in IP nergotiations to prepare the ground for funding of a venom reserach project |
Impact | Confidentiality agreement |
Start Year | 2015 |
Description | Cambridge Collaboration |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have provided (under NDA) the SOPs for the whole blood phagocytosis assay to Dr Andrew Conway-Morris who is an international expert in innate immune function in sepsis. |
Collaborator Contribution | Dr Conway-Morris is investigating a number of neutrophil function assays as part of his work and will compare our assay against other established assays (e.g. zymosan) in an attempt to determine optimal measures. |
Impact | None yet |
Start Year | 2016 |
Description | Co-developed of products by LSTM and Qiagen (In Vitro Diagnostics) |
Organisation | QIAGEN |
Department | QIAGEN (Netherlands) |
Country | Netherlands |
Sector | Private |
PI Contribution | Assay development, initial assay validation and testing of the rt-PCR assay in surveillance laboratories, Multiplex assay optimisation, and HDA assay development. |
Collaborator Contribution | Qiagen made a significant contribution to this project including a rotor gene qPCR system with 5 channel detection. This system has a transfer price of ~£25,000. All qPCR reaction mix, viral RNA extraction kits will be provided free of charge throughout the project, representing a significant outlay of about £15,000. Qiagen will also cover the costs of the CE mark request. |
Impact | Develop improved diagnostic assays for the simultaneous detection of CHK and dengue viruses. The outcomes expected are: 1. A multiplexed CHKV and DENV rt-PCR test, capable of the sensitive detection of both viruses and differentiation of DENV serotypes, which will be IVD CE certified for commercial release. 2. Performance data of the assay generated during comparative tests with "in house" rt-PCR assays and commercial ELISA tests on prospective fever cases in Ecuador and Brazil. 3. Extracted RNA from clinical specimens to enable the development of the qPCR and HDA assays at LSTM. 4. Design and initial testing of an isothermal HDA assay for CHKV. 5. Publications in international, peer reviewed, high impact factor journals. |
Start Year | 2015 |
Description | Collaboration to accelerate development of vaccines against MERS-CoV |
Organisation | M.C.I Animal Health |
Country | Morocco |
Sector | Private |
PI Contribution | My research team has contributed a leading rationally designed vaccine candidate, that has already shown promise in preliminary immunogenicity studies. |
Collaborator Contribution | Vincent Munster's group at NIAID's Rocky Mountain Laboratories is testing the efficacy of the vaccine using his established transgenic mouse model. IRED in Chad is providing camel immunisation and immunogenicity assessment. Vaccitech Limited, a recent University of Oxford spin-out with exclusive rights to our MERS vaccine, has provided co-funding to support camel challenge studies in Morocco. We have sent vaccine to both these institutions, and they will send back results from mutually agreed study designs. |
Impact | A single dose of the vaccine administered intramuscularly or intranasally has been shown to provide 100% efficacy against lethal challenge in mice. Analysis of antibody titres, viral titres and histopathology are currently underway. Dromedary camels are now being recruited into the study at IRED, Chad and vaccine and consumable shipment will soon commence. We expect to immunise in December 2016, with results expected as from January 2017. |
Start Year | 2016 |
Description | Collaboration to accelerate development of vaccines against MERS-CoV |
Organisation | National Institute of Allergy and Infectious Diseases (NIAID) |
Department | Rocky Mountain Laboratories |
Country | United States |
Sector | Public |
PI Contribution | My research team has contributed a leading rationally designed vaccine candidate, that has already shown promise in preliminary immunogenicity studies. |
Collaborator Contribution | Vincent Munster's group at NIAID's Rocky Mountain Laboratories is testing the efficacy of the vaccine using his established transgenic mouse model. IRED in Chad is providing camel immunisation and immunogenicity assessment. Vaccitech Limited, a recent University of Oxford spin-out with exclusive rights to our MERS vaccine, has provided co-funding to support camel challenge studies in Morocco. We have sent vaccine to both these institutions, and they will send back results from mutually agreed study designs. |
Impact | A single dose of the vaccine administered intramuscularly or intranasally has been shown to provide 100% efficacy against lethal challenge in mice. Analysis of antibody titres, viral titres and histopathology are currently underway. Dromedary camels are now being recruited into the study at IRED, Chad and vaccine and consumable shipment will soon commence. We expect to immunise in December 2016, with results expected as from January 2017. |
Start Year | 2016 |
Description | Collaboration to accelerate development of vaccines against MERS-CoV |
Organisation | Vaccitech Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | My research team has contributed a leading rationally designed vaccine candidate, that has already shown promise in preliminary immunogenicity studies. |
Collaborator Contribution | Vincent Munster's group at NIAID's Rocky Mountain Laboratories is testing the efficacy of the vaccine using his established transgenic mouse model. IRED in Chad is providing camel immunisation and immunogenicity assessment. Vaccitech Limited, a recent University of Oxford spin-out with exclusive rights to our MERS vaccine, has provided co-funding to support camel challenge studies in Morocco. We have sent vaccine to both these institutions, and they will send back results from mutually agreed study designs. |
Impact | A single dose of the vaccine administered intramuscularly or intranasally has been shown to provide 100% efficacy against lethal challenge in mice. Analysis of antibody titres, viral titres and histopathology are currently underway. Dromedary camels are now being recruited into the study at IRED, Chad and vaccine and consumable shipment will soon commence. We expect to immunise in December 2016, with results expected as from January 2017. |
Start Year | 2016 |
Description | Collaboration with Butantan |
Organisation | Butantan Institute |
Country | Brazil |
Sector | Public |
PI Contribution | We established collaborative links with the reference surveillance centres for the State of Sergipe and with Butantan Institute (Sao Paulo, Brazil) for the development of dengue, chikungunya and zika molecular assays |
Collaborator Contribution | Development of dengue, chikungunya and zika molecular assays |
Impact | Development of molecular assays in progress. |
Start Year | 2015 |
Description | Collaboration with Pfizer Innovator Award |
Organisation | Pfizer Inc |
Country | United States |
Sector | Private |
PI Contribution | As part of our Wellcome Trust Innovator Award, our team are making several hundred new PDE inhibitors and testing them against malaria parasites and PDE enzymes. |
Collaborator Contribution | As part of our Wellcome Trust Innovator Award, Pfizer have agreed to carry our ADME testing on selected compounds and are funding this through in-kind support. |
Impact | No outputs so far |
Start Year | 2019 |
Description | Collaboration with Smith College |
Organisation | Smith College |
Country | United States |
Sector | Academic/University |
PI Contribution | We are setting up experimental infections and providing samples for Smith College to evaluate new methodoogies for detection of parasite DNA in excreta |
Collaborator Contribution | Smith College is assisting with sample processing and applying new methodologies to the detection of parasite DNA in mosquito feces |
Impact | Abstracts submission to ASTMH meeting in 2016. Grant submission to Bill and Melinda Gates Foundation, Grant submisison to GCRF |
Start Year | 2015 |
Description | Collaboration with Xeroshield |
Organisation | Xeroshield |
Country | United Kingdom |
Sector | Private |
PI Contribution | Expertise in vector behaviour and molecular xenomonitoring |
Collaborator Contribution | Expertise in product development and design ideas |
Impact | This collaboration began in March 2016 and we have held one preliminary meeting with partners. Bruce Alexander visited my group on 9th March 2016 and we have finalised a plan for research activities. |
Start Year | 2016 |
Description | Epistem |
Organisation | Epistem |
Country | United Kingdom |
Sector | Private |
PI Contribution | Development of diagnostic probes for kdr resistance in An. gambiae |
Collaborator Contribution | Production of probes for Genedrive system |
Impact | Diagnostic probes for kdr resistance, pilot data for proof of principle use of probes with Genedrive technology. |
Start Year | 2014 |
Description | Godrej Group parnership |
Organisation | Epistem |
Country | United Kingdom |
Sector | Private |
PI Contribution | Developed an Indo-UK partnership to develop new diagnostics for insecticide resistance |
Collaborator Contribution | Godrej are the largest producer of houshold insecticide products in India. They are providing a product market and in country facilities for field research. The UK partner, Epistem, are producing the technology for new product development and providing exprtise and materials for the project. |
Impact | Early stage of project, no outputs as yet. |
Start Year | 2015 |
Description | Godrej Group parnership |
Organisation | Godrej Group |
Country | India |
Sector | Private |
PI Contribution | Developed an Indo-UK partnership to develop new diagnostics for insecticide resistance |
Collaborator Contribution | Godrej are the largest producer of houshold insecticide products in India. They are providing a product market and in country facilities for field research. The UK partner, Epistem, are producing the technology for new product development and providing exprtise and materials for the project. |
Impact | Early stage of project, no outputs as yet. |
Start Year | 2015 |
Description | Joint PhD Student with RedX Pharma |
Organisation | Redx Pharma Plc |
Country | United Kingdom |
Sector | Private |
PI Contribution | This is a joint initiative between LSTM and RedX Pharma to recruit a PhD student to undertake a project at Liverpool and Alderley Park |
Collaborator Contribution | This is a joint initiative between LSTM and RedX Pharma to recruit a PhD student to undertake a project at Liverpool and Alderley Park |
Impact | None as yet |
Start Year | 2016 |
Description | KIIT |
Organisation | Kalinga Institute of Industrial Technology (KIIT) University |
Country | India |
Sector | Academic/University |
PI Contribution | Links made through collaboration with Godrej Industries to develop a three way Industry - UK/India academic partnership for research and training. |
Collaborator Contribution | KIIT set-up high level meeting with LSTM Director (Hemingway) and Godrej to initiate talks on partnershp opportunities |
Impact | MOU and high level meetings with LSTM/Godrej/KIIT management. Multidisciplinary, Educational/ research/ industry |
Start Year | 2016 |
Description | LSHTM |
Organisation | London School of Hygiene and Tropical Medicine (LSHTM) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have led the development of the collaboration with LSHTM for a consortium that includes other national HEI partners all with a focus to support pump priming activities in the translational space relevant for infections that are significant to disadvantaged populations in the UK and abroad. |
Collaborator Contribution | The partner is an active member of the described consortium that gives significant in kind support with respect to resource and technical expertise. |
Impact | Please see Research Fish for CiC and IAA awards. |
Start Year | 2011 |
Description | MRC CiC PDE project GSK |
Organisation | GlaxoSmithKline (GSK) |
Country | Global |
Sector | Private |
PI Contribution | Screening PDE inhibitors for activity against malaria parasites |
Collaborator Contribution | Provision of compounds |
Impact | No outputs as yet. Data are being generated. |
Start Year | 2015 |
Description | MRC CiC PDE project Pfizer |
Organisation | Pfizer Inc |
Country | United States |
Sector | Private |
PI Contribution | Screening PDE inhibitors for activity against malaria parasites |
Collaborator Contribution | Provision of ~600 compounds |
Impact | This project led to 2-year Wellcome Innovator Award in which Pfizer provided in-kind funding to carry out ADME. |
Start Year | 2015 |
Description | MRC CiC PDE project Salvensis |
Organisation | Salvensis |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | We work together on screening GSK and Pfizer PDE inhibitors for activity against malaria parasites |
Collaborator Contribution | Chemistry and drug discovery expertise. |
Impact | No outputs as yet |
Start Year | 2015 |
Description | MRC_CiC_CRro_nanoP |
Organisation | Blueberry Therapeutics |
Country | United Kingdom |
Sector | Private |
PI Contribution | Unchanged from previous report |
Collaborator Contribution | Unchanged from previous report |
Impact | Experimental work now complete. Stable model of macrophage infection by S. Typhi created and observed on high throughput imaging platforms. Experimental infection and treatment of cell lines now complete and data being analysed. RA has been awarded PhD and secured LSTM director's catalyst award to continue in post Manuscripts now in preparation The findings from this work are more fundamental to typhoid biology than any of us expected, but are no less relevant to therapeutic intervention design |
Start Year | 2015 |
Description | MRC_CiC_CRro_nanoP |
Organisation | Blueberry Therapeutics |
Country | United Kingdom |
Sector | Private |
PI Contribution | The phase based at LSTM commenced on 1st April 2016. We have developed a model for evaluating the intracellular compartment during Salmonella Typhi infection and are currently completing experiments using ceftriaxone/nanopolymer combinations. This work is on course to finish in April 2018. |
Collaborator Contribution | Coformuations of ceftriaxone with nanopolymer - this work is now complete manuscript in preparation |
Impact | Research still in progress, but as of February 2017 is nearing completion. Stable model of macrophage infection by S. Typhi created and observed on high throughput imaging platforms. Experimental infection and treatment of cell lines now complete and data being analysed. |
Start Year | 2015 |
Description | Media perfusion assay development for Leishmaniasis |
Organisation | Kirkstall Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | I have used the media perfusion system bought from Kirkstall Ltd to conduct an in-depth analysis of how the process of infection with Leishmania parasites is effected by media perfusion, used to simulate both interstitial fluid flow and blood flow. I have used the QV900 system to test four standard drugs against infected macrophages in comparison with a static control. I have conducted drug accumulation studies in the system to try and elucidate the reasons for the results we have seen previously. |
Collaborator Contribution | Kirkstall Ltd have provided training and support of use of the media perfusion systems they manufacture. They have helped design products to suit our experimental needs and helped us gain many useful contacts in the research area. |
Impact | Experimentation with the media perfusion system to study the effect of media flow simulating either interstitial or blood fluid flow has been shown to reduce the overall infection caused by Leishmania parasites when compared to a static system. The higher the flow rate the lower the infection is overall after 72 hours of incubation. When testing standard drugs in this system we have found that the media perfusion alters the potency of the drugs activity. To achieve the same reduction in parasitaemia a higher concentration of drug must be used in the flow system. To enhance our understanding we have conducted drug accumulation studies that show less drug is accumulated under flow conditions. |
Start Year | 2013 |
Description | Molecular characterisation of insecticides and combination effects against mosquitoes |
Organisation | Bayer |
Country | Germany |
Sector | Private |
PI Contribution | Created and supervised PhD project |
Collaborator Contribution | Bayer hosted PhD student and paid research costs in Germany and UK student fees, IVCC covered UK research costs |
Impact | 4 publications - DOI's 10.1016/j.pestbp.2022.105051 10.1016/J.CRPVBD.2021.100041 https://doi.org/10.1016/j.ibmb.2022.103813 10.1016/j.pestbp.2023.105356 multidisciplinary - molecular biology, biochemistry and pharmacology of insecticide metabolism, |
Start Year | 2018 |
Description | Molecular characterisation of insecticides and combination effects against mosquitoes |
Organisation | IVCC |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Created and supervised PhD project |
Collaborator Contribution | Bayer hosted PhD student and paid research costs in Germany and UK student fees, IVCC covered UK research costs |
Impact | 4 publications - DOI's 10.1016/j.pestbp.2022.105051 10.1016/J.CRPVBD.2021.100041 https://doi.org/10.1016/j.ibmb.2022.103813 10.1016/j.pestbp.2023.105356 multidisciplinary - molecular biology, biochemistry and pharmacology of insecticide metabolism, |
Start Year | 2018 |
Description | Neutrophil bead assay: Paediatric validation |
Organisation | Alder Hey Children's NHS Foundation Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | Alder Hey: Two senior investigators have partnered with us to provide access to samples from septic children in order to extend the usefulness of the assay into this age group Clatterbridge: Commitment from oncologist to assessing the potential of this assay for identifying patients at risk of neutropenic sepsis |
Collaborator Contribution | Alder Hey: Development of paediatric protocol, and submission of REC application. Commitment of nursing support to consent and obtain blood samples Clatterbridge: Collaborative development of a sampling strategy to identify patients with haematological malignancies receiving initial immunosuppressive treatment. This will be developed into an application for further funds to enable cross-sectional sampling of high risk patients in which the utility of the assay can be assessed |
Impact | No output yet |
Start Year | 2015 |
Description | Neutrophil bead assay: Paediatric validation |
Organisation | The Clatterbridge Cancer Centre NHS Foundation Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | Alder Hey: Two senior investigators have partnered with us to provide access to samples from septic children in order to extend the usefulness of the assay into this age group Clatterbridge: Commitment from oncologist to assessing the potential of this assay for identifying patients at risk of neutropenic sepsis |
Collaborator Contribution | Alder Hey: Development of paediatric protocol, and submission of REC application. Commitment of nursing support to consent and obtain blood samples Clatterbridge: Collaborative development of a sampling strategy to identify patients with haematological malignancies receiving initial immunosuppressive treatment. This will be developed into an application for further funds to enable cross-sectional sampling of high risk patients in which the utility of the assay can be assessed |
Impact | No output yet |
Start Year | 2015 |
Description | Novel antibiotic nano formulations |
Organisation | Blueberry Therapeutics |
Country | United Kingdom |
Sector | Private |
PI Contribution | Imaging and PK-PD platform to screen novel antibiotic formulations against Salmonella |
Collaborator Contribution | nano-formulation expertise and materials |
Impact | none yet |
Start Year | 2015 |
Description | PK/PD studies ( Drug accumulation) |
Organisation | Pharmidex |
Country | United Kingdom |
Sector | Private |
PI Contribution | Drug accumulation studies were conducted using a media perfusion system. LSHTM used the media perfusion system and conducted a drug assay that was then placed under flow conditions to compare to a static system. LSHTM completed the assay and extracted drug samples from the cells after different times. |
Collaborator Contribution | Pharmidex took the samples and analysed them to find exact drug concentrations in the nanomolar range. |
Impact | Drug accumulation studies have been completed for two standard drugs. A significant difference is seen in the concentration of drug within the cells between the static and the flow systems. |
Start Year | 2016 |
Description | Partnership with Medicines for Malaria Venture Innovator Award |
Organisation | Medicines for Malaria Venture (MMV) |
Country | Switzerland |
Sector | Charity/Non Profit |
PI Contribution | We have synthesised ~300 compounds and tested these on malaria parasites and enzyme fractions as part of our Wellcome Innovator Award. |
Collaborator Contribution | MMV are giving us access to a number of assays their malaria drug discovery labs worldwide |
Impact | No outputs as yet |
Start Year | 2019 |
Description | Partnership with Salvensis Innovator Award |
Organisation | Salvensis |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | We are testing newly synthesised compounds for activity against malaria parasite phoisphodiesterases |
Collaborator Contribution | Salvensis are managing chemical synthesis |
Impact | None as yet but ~300 compounds have been synthesised and tested for activity against the parasite and against PDE enzymes |
Start Year | 2019 |
Description | UKHSA |
Organisation | Public Health England |
Department | Public Health England Porton Down |
Country | United Kingdom |
Sector | Public |
PI Contribution | We have led the development of the collaboration with UKHSA for a consortium that includes other national HEI partners all with a focus to support pump priming activities in the translational space relevant for infections that are significant to disadvantaged populations in the UK and abroad. |
Collaborator Contribution | The partner is an active member of the described consortium that gives significant in kind support with respect to resource and technical expertise. |
Impact | Please see Research Fish for CiC and IAA awards. |
Start Year | 2011 |
Description | University of Oxford |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have led the development of the collaboration with Oxford for a consortium that includes other national HEI partners all with a focus to support pump priming activities in the translational space relevant for infections that are significant to disadvantaged populations in the UK and abroad. |
Collaborator Contribution | The partner is an active member of the described consortium that gives significant in kind support with respect to resource and technical expertise. |
Impact | Please see Research Fish for CiC and IAA awards. |
Start Year | 2011 |
Description | VIT |
Organisation | Vellore Institute of Technology University |
Country | India |
Sector | Academic/University |
PI Contribution | Research presentation and visit to VIT in 2014, leading to research and teaching links with Dept of Nanobiotechnology. Made links between LSTM International Education and Knowledge Exchange Initiatives (Michael Lurie) and VIT Director, International Relations for institutional cooperation and student exchange |
Collaborator Contribution | Awarded Adjunct Professorship to M Paine. Progressed instututional agreements. |
Impact | Adjunct Professorship (M Paine) MOU High level meeting (Nov 2015) for Institutional teaching partnership Multidisciuplinary collaboraton - Research/ educational |
Start Year | 2014 |
Description | VIT |
Organisation | Vellore Institute of Technology University |
Country | India |
Sector | Academic/University |
PI Contribution | Research presentation and visit to VIT in 2014, leading to research and teaching links with Dept of Nanobiotechnology. Made links between LSTM International Education and Knowledge Exchange Initiatives (Michael Lurie) and VIT Director, International Relations for institutional cooperation and student exchange |
Collaborator Contribution | Awarded Adjunct Professorship to M Paine. Progressed instututional agreements. |
Impact | Adjunct Professorship (M Paine) MOU High level meeting (Nov 2015) for Institutional teaching partnership Multidisciuplinary collaboraton - Research/ educational |
Start Year | 2014 |
Description | Bluedot Festival; Can malaria be eliminated from the bluedot before we reach mars? |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Bluedot is an annual music/ science festival held at Jodrell Bank that attracts 12 - 15,000 people. The talk on recent advances in malaria control held in a 200 seater auditorium was near capacity and attracted a diverse audience and age range (toddlers to retired). The presentation generated a great deal of interest and questions, particularly from teenage/ early 20's people citing interests in career opportunities in tropical medicine. |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.discoverthebluedot.com/profile/can-malaria-be-eliminated-from-the-blue-dot-before-we-rea... |
Description | Industry visit |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | Visit to LSTM laboratories by a group of 15 scientists, business people and funders involved in the development of new products to control mosquito vectors of disease. Include small and large companies including Mitsui, BASF, Vestergaard, Syngenta, BMGF. Discussions revolved around the application of research on new diagnostic insecticide resistance probes, transgenic mosquitoes, analytical methods for quality assurance of new products, future direction of vector control reseach |
Year(s) Of Engagement Activity | 2023 |
Description | Invited Speaker at 1st International Congress of Vector-Borne Diseases. 10-11 Sep 2016 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I was invited to deliver a lecture on Vector-Borne diseases and discuss the research and progress of my group, focusing on vaccine development. Conference was in Zamora, Michoacan, Mexico. More than 500 attendees including the ministry of Health of Mexico and Michoacana, as well as postgraduate students and practitioners. |
Year(s) Of Engagement Activity | 2016 |
Description | Invited Speaker at the "Closing the Global Health Divide through Partnership Driven Innovation Meeting" |
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 | The event represented a collective call for greater cross-border and cross-sector collaboration to ensure global preparedness for the inevitable resurgence of infectious diseases that disproportionally affect the poorest of the poor in developing countries. A series of presentations and interactive panels articulated the need for partnerships in global health and explored the challenges associated with R&D for infectious diseases. |
Year(s) Of Engagement Activity | 2014 |
Description | Kensington and Chelsea Science Festival |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | 17th Oct 2015, Kensington and Chelsea Science Festival, Kensington Town Hall, London. "Tropical diseases: new solutions for tackling old problems": the talk wqas to a braod audience of ~30/40 people, including Major of Kensington/ Chelsea, school children, public and councillors. The talk provoked discussion about the use of insecticides in disase control. |
Year(s) Of Engagement Activity | 2015 |
URL | https://www.youtube.com/watch?v=dlDmTngEW7w&feature=share |
Description | Keystone Symposia conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | The meeting was focused on One Health and had talks on veterinary and human vaccinology. I was invited to give a talk on the use of viral vectors for co-development of vaccines that can be used in both humans and animals. MERS is an excellent example of one such disease indication. |
Year(s) Of Engagement Activity | 2016 |
Description | Poster presentation UK Clinical Research Facility Conference Glasgow 2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Presented study results using the assay refined and validated in the MRC CiC award 2015 - blood taken from children admitted to paediatric intensive care with sepsis |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.cvent.com/events/uk-clinical-research-facilities-13th-annual-conference/event-summary-a1a... |
Description | Presentation at MRC CiC NTD consortium meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | I gave a presentation on the results of the project of which the MRC CiC was granted for us to complete. In attendance were other grant holders in both academia and industry. Also potential applicants who were actively seeking funding were able to see some of the results and progress of a existing project. |
Year(s) Of Engagement Activity | 2017 |
Description | Series of Rational Drug Discovery lectures (Undergraduate) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | To provide a better understanding how the students can translate their science / research activities to have more impact in terms of generating and developing products such as drugs, insecticides etc. |
Year(s) Of Engagement Activity | 2018 |
Description | Series of rational drug discovery lectures (Post Graduate) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | To provide a better understanding how the students can translate their science / research activities to have mor eimpact in terms of generating and developing products such as drugs, insecticides etc. |
Year(s) Of Engagement Activity | 2018 |