Development of methods for robust gene integration into native gut E. coli
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
ABSTRACT The objective of this proposal is to develop conjugative methods for rapidly and reliably integrating genes into diverse native bacteria isolates from both mice and humans. This will enable the creation of engineered native bacteria (ENBs) which can be used to study the gut microbiome and develop new therapeutics for chronic diseases. Compared to lab strains of bacteria and other bacterial strains used for live bacterial therapeutics, native bacteria have the unique ability to engraft and colonize the host long term. Therefore, ENBs have great potential as a platform technology to advance our understanding of the gut microbiome from a mechanistic level and as a therapeutic for the treatment of disease. However, engineering native bacteria remains challenging due to their inherent resistance to genetic manipulation. This research aims to address these issues by developing protocols that facilitate high- throughput and site-specific genome integration in native bacterial strains. The investigators will develop two protocols to address this problem. For Aim 1 the researchers will develop a protocol using Tn7 transposon integration for high throughput gene integration in 42 strains of native bacteria (e.g. Escherichia coli, Citrobacter spp., Enterococcus spp.) isolated from the gut of mice and humans in different disease contexts. This will result in a collection of validated chassis bacteria that are ready for use in high-throughput synthetic biology-based approaches by multiple collaborating labs across several institutions. For Aim 2 the investigators will develop a protocol for iterative genome integration of genes using conjugation and phage recombinases in both mouse and human gut native E. coli. The investigators will engineer a butyrate biosynthesis pathway into native E. coli. This protocol will allow for the introduction of complex, multi-gene pathways into ENBs. The expected outcomes of this research are validated chassis strains and new techniques that will unlock high-throughput and reliable construction of ENBs. This will have a positive translational impact by advancing the development of ENBs as therapeutics for the treatment of chronic diseases. The proposed work directly aligns with the mission of the National Institute of Allergy and Infectious Diseases (NIAID), specifically the development of new tools to understand diseases and its prevention and treatment. By enabling researchers with the methods to engineer native bacterial strains more effectively, this proposal will facilitate the creation of new ENB based therapeutic approaches for chronic diseases, including metabolic and inflammatory disorders.
Grant Summary
Development of methods for robust gene integration into native gut E. coli is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $439K for university, nonprofit, healthcare org. Applications are due 2028-05-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $439K
2028-05-31
- 1Confirm your organization is eligible for Development of methods for robust gene integration into native gut E. coli from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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Development of methods for robust gene integration into native gut E. coli: Frequently Asked Questions
Who is eligible for the Development of methods for robust gene integration into native gut E. coli?
Development of methods for robust gene integration into native gut E. coli is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Development of methods for robust gene integration into native gut E. coli provide?
Development of methods for robust gene integration into native gut E. coli provides up to $439K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Development of methods for robust gene integration into native gut E. coli deadline?
Applications for Development of methods for robust gene integration into native gut E. coli are due 2028-05-31 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Development of methods for robust gene integration into native gut E. coli?
To apply for Development of methods for robust gene integration into native gut E. coli, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.