Deadline: 13 May 2015
The Bill & Melinda Gates Foundation is inviting new ideas/proposals that addresses Newborn and Infant Gut Health through Bacteriophage-Mediated Microbiome Engineering. 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. An example of a more early-stage proposal would be the use of bacteriophages to develop a dynamic model for the bacterial determinants of gut health. This could include, for example, targeted killing of specific bacterial strains or classes of strains within the gut, titrating the treatment efficacy from moderate reduction to complete elimination of targeted strains, and the concomitant monitoring and modeling of how the microbial community responds to such disruption. An example of a more applied proposal would be that of testing a bacteriophage intervention in a relevant model, where the treatment would be developed based on a mechanistic model that considers pharmacokinetics, delivery characteristics, microbiome dynamics, signaling, inflammation, etc.
Approaches of funding:
- Systems-level approaches that address many of the criteria below are of particular interest.
- Selection and/or engineering of pathogen-specific bacteriophage or bacteriophage cocktails;
- 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;
- Studies aimed at using bacteriophage to understand the mechanistic and/or dynamic principles underlying microbiome-host health and pathology, especially under acute disruption;
- 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;
- Studies investigating timing, formulation, and/or route of administration of bacteriophage therapies.
Proposals must do all of the following:
- 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.;
- Strategies involving the use of engineered bacteriophage or gene therapy must include a discussion on overcoming regulatory hurdles.
Approaches not 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;
- 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.
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