- Total grants
- Total funders
- Total recipients
- Earliest award date
- 24 Jan 2017
- Latest award date
- 07 Dec 2017
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Following a positive response to the preliminary submission for grant funding to establish a Dengue Controlled Human Infection Model (Dengue-CHIM ) in Ho Chi Minh City, Vietnam, I am submitting this request for a small grant to assist in refining and developing the main proposal prior to final submission in March 2018. During this pre-submission phase I plan to employ an experienced post-doctoral immunologist to carry out a) a scoping review of the current landscape of dengue vaccines in development, and b) a review exploring the current understanding of the immune response to/protection from DENV infection and disease, particularly focusing on immune correlates of protection. This will be the first application of a Dengue-CHIM approach in any dengue endemic setting, and raises a number of important bioethical concerns. Therefore I also plan to employ a Vietnamese social science research assistant for a period of 4 months to engage with key Vietnamese stakeholders to discuss the important issues surrounding endemic setting CHIMs, conduct preliminary informal interviews with these individuals, and help to develop the agenda for a 2 day workshop focused on Bioethics and Stakeholder Engagement related to endemic setting CHIMs that will take place in early March.
Diarrhoea remains a major cause of childhood morbidity and mortality globally. The vast majority of the 2 billion annual diarrhoeal infections occur in low and middle-income countries (LMICs). Members of the genus Shigella are key agents of diarrhoea in LMICs, and S. sonnei is replacing S. flexneri as the predominant species globally. There is a necessity to improve our knowledge of S. sonnei infections in LMICs, with a specific requirement to better understand host-pathogen interactions and the natural history of disease in a setting where the organism is well understood, well described, and associated with a significant disease burden. Therefore, we aim to establish a Controlled Human Infection Model (CHIM) of S. sonnei diarrhoea in healthy Vietnamese adults. This is an innovative project will be the first CHIM study conducted at the Vietnam MOP. Therefore, it is imperative that the project is carefully designed in consultation with all relevant stakeholders. In order to ensure that the proposal is developed to the required standard in the timeframe available, I am requesting funds to employ an international postdoctoral assistant, with a background in microbiology and clinical research on a consultancy basis.
We wish to apply for funds to develop the malaria CHIM application. These are for a Co-investigators/stakeholders meeting to be held in Bangkok, Thailand, on 30th and 31st January 2018 and to support a writing meeting of the PIs in February 2018 in Kilifi, Kenya.
The human microbiota provides protection against pathogens via colonisation resistance. However, this resistance is not guaranteed, especially in the face of antibiotic treatment that suppresses the microbiota. My goal is to engineer communities for robustness to both antibiotics and pathogens. The challenge is that communities are complex systems containing many interacting and evolving species, making them challenging to predict and understand. Aim 1. Develop theory and analysis tools for complex microbial communities We will develop complex systems theory and quantitative tools to meet the challenges of understanding and engineering diverse communities. Aim 2. Apply theory to in-vitro gut communities We will apply our theory and test our ability to design gut communities that are robust to either antibiotic treatment, colonisation by the enteric pathogen Salmonella Typhimurium, or both. We will then study community and pathogen evolution: can a pathogen easily resist a probiotic community? Will the community evolve in response? Aim 3. Apply theory to S. Typhimurium pathogenesis We will study S. Typhimurium in gnotobiotic mice and test our ability to design robust communities in vivo. We will ask if S. Typhimurium can overcome in vivo colonisation resistance.
Bridging funds for transition to ISARICC's 2018-2022 Strategic Plan
Modelling the impact of poor quality antimicrobials on patient outcome and drug resistance – a pilot study to inform policy in the absence of empirical data 30 Sep 2017
Antimicrobial resistance (AMR) is an increasingly serious and pressing global public health problem. Poor antimicrobial quality is increasingly realised as an important rectifiable impediment to global public health. There has been little discussion or evidence as to its comparative importance, in relation to other drivers such as poor prescribing and adherence, for both poor patient outcomes and AMR. In the absence of field data on the relationship between AMR and antimicrobial quality, mathematical modelling based on pharmacokinetic-pharmacodynamic relationships and rates of genetic change provides estimates which can be used to predict outcomes and inform policy. We propose a two phase modelling approach examining how poor quality essential medicines may affect patient outcomes and resistance selection and spread, modelling in Phase 1 antimalarials and in Phase 2 anti-tuberculosis and anti-hepatitis C medicines. This pilot project will build on the existing Wellcome investment in the Mahidol Oxford Research Unit (MORU) Network (though core funding) and the Infectious Diseases Data Observatory (through the MAPQAMP Biomedical Resources grant and core funding) for modelling, PK/PD and medicine quality resources and skills. The growing interest in medicine quality by nations and international organisations and the invitation by the WHO Member State Mechanism (on medicine quality) to the IDDO/MORU Medicine Quality Group to be a stakeholder, facilitates synergistic discussions with multiple partners and nations. We are also discussing expanding our collaboration with the United States Pharmacopeia PQM program on medicine quality & AMR. We are organising the first Conference on Medicine Quality & Public Health for September 2018 and we intend that the initial results from this work would be presented at this meeting. This project will therefore give the first objective evidence, rather than opinion, on the importance, or otherwise, of medicine quality on patient outcome and AMR, in comparison to poor adherence and poor prescribing. It will link in extremely well with the diverse activities of the MORU Network, IDDO, WHO, USP and diverse other stakeholders and be opportune for influencing policy for both medicine quality and AMR. This project will be linked to the parallel project proposed to Wellcome by Dr Elizabeth Pisani on ‘Understanding the political barriers to tackling sub-standard and falsified medicines’.
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that express a semi-invariant, MR1-restricted, T cell receptor (TCR). In humans, they comprise 1-10% of peripheral blood T cells and are enriched at mucosal sites. MAIT cells display characteristic expression of several surface molecules and transcription factors, and a typical cytokine response to stimulation. Therefore, they have been regarded as relatively homogeneous. However recent evidence indicates diversity in TCR expression and function that varies between tissues and individuals. Further investigation is required to understand the extent of MAIT cell heterogeneity and tissue-specific functionality. In several human autoimmune and inflammatory diseases, MAIT cells are activated or show phenotypic changes. How the altered cytokine environment in such diseases can modulate MAIT cell function remains to be determined. The key goals of my research are to provide a comprehensive assessment of diversity and plasticity in MAIT cell function, and to understand the factors that regulate this. To achieve this, I will use a combination of approaches including single-cell mRNA sequencing and epigenetic analysis, and will explore MAIT cells from varied settings encompassing resting and activated, tissue-localised, and disease-associated MAIT cells. This will provide important insights into their physiological role both in health and disease.
With the rise in multidrug resistance as a result of broad spectrum antibiotic use, bacteriocins have received attention as potential new antibiotics. Bacteriocins are bacterial toxins that kill closely related strains and species. Pyocin S5, a bacteriocin targeting Pseudomonas aeruginosa, a leading cause of multidrug resistant nosocomial infections, was shown to be effective against pneumonia in mice. Pyocin S5 depends on the iron receptor FptA and kills cells by depolarizing the inner membrane. Little else is known about its mode of action. Pyocin S5-producing cells harbour a gene encoding a small immunity protein, predicted to localize to the inner membrane, which protects from the action of this pyocin. In this PhD project, I aim to investigate the molecular mechanism of pyocin S5 binding to P. aeruginosa cells, its mechanism of translocation to the periplasm and the immunity protein’s mode of action. These aims will be approached using a combination of structural and biophysical methods as well as functional assays and a variety of fluorescence microscopy techniques.
The MYRIAD Project: Exploring Mindfulness and Resilience in Adolescence
The Wellcome Trust Thailand Major Overseas Programme’s central aim is to improve health and reduce the human disease burden in the developing world. Its strategic objectives are: The development of people and institutions: mentoring world-class clinicians and scientists Disseminating high-quality research evidence, locally and globally Strengthening governance, management and financial planning, thus building operational excellence in tackling tropical diseases Public engagement (PE) & outreach with the communities who host us, in turn inspiring and involving current and future generations in medical research This application pertains to the last strategic objective of the programme. The "must-do" engagement activities are part of the Thailand Major Overseas Programme core grant 2015 -2020. In April 2016, the programme received a PPE award (£673,180) to build a core PE team and to pilot some "smart-to-do" and "wise-to-do" activities in years 1 and 2 of the core grant and with a view of shaping the PE activities for years 3 to 5. The core PE team is led by Ass. Prof. Phaik Yeong Cheah, who is co-PI on this application. This application is for PE activities in years 3 to 5 based on learnings from our pilot projects and to grow further the PE capacity within the programme.
In 2015 the WT Major Overseas Programme Vietnam was awarded a renewal of its Core funding. The MOP has a history of successful public engagement, funded through International Engagement awards and from industry sponsorship. However, with the introduction of the Provisions for Public Engagement funding scheme, we applied for funding for engagement at an institutional level, enabling us to create a 5-year strategic plan for developing engagement capacity within the MOP and in the region. Now, 20 months into the award, we reflect on activities to date, and plan strategically for the second part of the programme. The 5-year public engagement programme includes a schools engagement programme (SEP) and a capacity building programme (CBP), both of which have proved to be very successful and highly valued by our local government and school partners. The third focus has been to develop researcher capacity for engagement – through small grants and offering training and mentoring. We have had a good uptake of these ‘seed awards’ from MOP researchers and increasing interest in engagement from researchers at local institutes in Vietnam. Schools Engagement: The SEP has been very successful (http://www.mediafire.com/file/td3kaomtu9t7ia7/Application.7z), in particular: afterschool science clubs; weekly science articles in a children’s magazine; science theatre; and lab visits enabling young people to interact with scientists. The SEP has also included ‘I’m a scientist, Get me out of here’ - a competition linking children and scientists, run with Gallomanor UK (https://imascientist.org.uk) (https://www.youtube.com/watch?v=n--SJOtFm1w). Capacity building: The CBP was developed in recognition that much of the ‘front-line’ contact with patients and communities enrolled in clinical trials or cohort studies is from hospital or government study staff. In response we have started a CBP to train and support hospital health care workers (HCMC), community-based data collectors (Nepal) and local vets (in provinces where we conduct research on zoonosis). As the funding for the IAS project and other awards come to an end, we need additional funding to support the current PE team. This application is for additional staff salary costs and to run PE workshops to develop engagement capacity across the region.
DNA origami: how do you fold a genome? 30 Apr 2017
Recent advances in DNA sequencing technology mean that it is now possible to identify genetic variants in patients with specific diseases which either cause or alter their risk of developing that disorder. However, linking these variants to the genes they regulate and the symptoms of the condition itself is time-consuming and challenging. The overarching aim of this project is to develop high-throughout methods to systematically investigate the impact of genetic variants associated with specific diseases on cell function and human health. This will be achieved via collaboration between several groups within the University of Oxford and multidisciplinary external groups, each bringing their own specific field of expertise relevant to the overall aims of the project. Over the past three years, we have developed and refined high-throughput techniques to link genetic variants to the genes they control, and analyse how and why these variants impact the activity of their target gene. Now that we have established these methodologies and associated computational analysis pipelines, we will apply these techniques to variants associated with various conditions during the next two years of the award. In the first instance, these will be disorders associated with red blood cells, multiple sclerosis, and type 2 diabetes. The final stage of the project is to optimize recently developed genome editing techniques to correct any variants that are found to have a functional impact on the condition in question. This will serve two purposes; first it will prove that the variants influence gene regulation and second it will provide the first steps to establishing proof-of principle for gene editing as a potential therapeutic opportunity. Of particular importance to the interpretation of this work will be ongoing basic research in modeling and visualization of how gene activity is regulated in the 3D space of the nucleus, which will aid our understanding of how these specific variants affect the activity of distant genes. Using state of the art methods to visualize and interact with the DNA molecule in three dimensions represents a unique opportunity to intuitively explain these complex but universally important concepts to the public.
Healing Heathen Lands: Protestant Missions and Public Health in British India, 1855-1956 17 Jul 2017
This project will explore the role of Protestant missions in the making of British Indian public health by tracing the interactions between evangelical, colonial and vernacular sources. It will argue that Protestant missionaries in South Asia did not merely play a complementary role to imperial biomedicine. It will examine the ways in which missions contributed towards shaping colonial health policies as well as knowledge of colonial disease and treatment. The project would also explore the extent to which Indians and their knowledge was involved in medical missions. This work will add on to histories of imperial medicine, international health, global history, colonial Christianity and postcolonial studies. The key goal of the project is to produce a monograph explaining the distinctiveness and significance of Protestant missionary medicine in South Asia. The project will be contributing to the emerging literature on British voluntary religious organisations in the making of imperial public health. It will also contribute to the broader literature on the relationship of modern science and medicine with Christianity.