Deadline: 11 November 2015
The Bill & Melinda Gates Foundation is inviting new ideas/proposals that addresses Newborn and Infant Gut Health through Bacteriophage-Mediated Microbiome Engineering under its 16th round of Grand Challenges Explorations (GCE). The Challenge is an opportunity to leverage decades worth of progress in biotechnology, including high-throughput sequencing, gene synthesis, advanced omics, and systems biology, to develop a novel bacteriophage-based tool to probe, modify, and ultimately foster healthy gut function through a healthy gut microbiome – one that is complementary to nutritional and chemotherapeutic approaches.
The goal of this topic is to support all stages of development of bacteriophage-mediated strategies for microbiome engineering in children under two years of age, as a means to reduce the number of cases of environmental enteropathy in low-resource settings.
- The pharmacokinetics and pharmacodynamics of phage therapies – how complete is pathogen elimination and over what timescale?
- The combination of empirical “subtractive” experiments in model systems, omics, and computational modeling to help understand the implications of acute microbial community disruption, the presence of new and high-titer bacteriophage, the release of endotoxins, etc. This could include modeling studies on:
- The response of the microbial community (e.g. through metagenomics);
- The immunogenic response of the host (e.g. through transcriptomics);
- Chemical signaling within the microbial community and between the microbial community and the host (e.g. through metabolomics).
What will be considered for funding:
- Systems-level approaches that address many of the criteria below are of particular interest.
- Studies aimed at using bacteriophage to understand the mechanistic and/or dynamic principles underlying microbiome-host health and pathology, especially under acute disruption;
- Strategies to mitigate the evolution of resistance of microbial pathogens to introduced bacteriophage;
- Modulation/optimization of the persistence and/or efficacy of bacteriophages in the newborn and/or infant gut;
- Development of relevant animal models for bacteriophage modeling and efficacy studies;
- Development of bacteriophage preparations that reduce or eliminate endotoxin exposure to the gut, from both the bacteriophage preparation itself and resulting from bacterial lysis;
- Proposals that identify regulatory risks for bacteriophage-based tools or therapies, and propose specific technical solutions for mitigating those risks;
- Selection and/or engineering of pathogen-specific bacteriophage or bacteriophage cocktails.
Proposals must do all of the following:
- Strategies involving the use of temperate bacteriophage must include a discussion on the mitigation of lysogen immunity to superinfection and generalized transduction;
- Convey a clear and testable hypothesis for how the innovation will measurably improve gut function, mitigate environmental enteropathy, or inform/enable future strategies to do so;
- Outline a clear measurement and evaluation plan for each component;
- Be relevant to the newborn or infant (less than two years old) gut;
- Be relevant to the developing world, especially on the basis of cost. This includes cost of preparation, delivery, stability, administration, etc.;
Fields Not be considered for funding:
- Ideas that are not directly relevant to developing countries;
- Ideas without a clearly articulated and testable hypothesis and metrics;
- Literature reviews or market studies;
- Incremental improvements over existing technologies;
- Proposals, or portions of proposals, for scale-up of existing preparations or business development;
- Ideas that address diseases not directly relevant to environmental enteropathy;
- Studies only on bioethics and/or regulatory issues. Applicants interested in these areas should consider partnering with others;
- Applications only proposing a screen or selection;
- Strategies that do not involve bacteriophage;
- Strategies aimed at killing pathogens without consideration of (1) microbiome dynamics, (2) the evolution of resistance, and (3) gut function consequences;
- Broad-spectrum antibacterial strategies;
- Ideas for which a relevant indicator of success cannot be demonstrated within the scope of the GCE Phase 1 award ($100,000 over 18 months);
- Solely infrastructure or capacity-building initiatives;
- Basic research without clear relevance to the goals of this topic.
For more information about this grand challenge, please visit GC Addressing New Born.