Key Dates

Related Announcements

• May 08, 2024 - Academic Research Enhancement Award (AREA) for Undergraduate-Focused Institutions (R15 Clinical Trial Not Allowed). See NOFO PAR-24-152.
• January 10, 2022 - Research Enhancement Award Program (REAP) for Health Professional Schools and Graduate Schools (R15 Clinical Trial Not Allowed). See NOFO PAR-22-060.
• May 07, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195.
• May 05, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.
• November 25, 2020 - NIDCR Small Grant Program for New Investigators (R03 Clinical Trial Not Allowed). See NOFO PAR-21-084.

Issued by

National Institute of Dental and Craniofacial Research (NIDCR)

Purpose

The National Institute of Dental and Craniofacial Research (NIDCR) is issuing this Notice of Special Interest (NOSI) to encourage research to better understand bacteriophage biology in the oral cavity and to support eventual development of therapeutics. Despite the high abundance of bacteriophage in the oral cavity, they continue to be overlooked as mediators of health and disease. An increased understanding of the role of bacteriophage in the oral cavity could lead to the development and use of phage therapy.

Background

The human oral cavity provides a portal of entry for viruses and bacteria. Metagenomics studies have identified a large population of viruses in the oral cavity, many of which were identified as bacteriophage--up to 10⁸ phages exist in 1 milliliter of human saliva. Phages specific for bacteria in the oral cavity, including Lactobacillus, Actinomyces, Aggregatibacter, Fusobacterium, Enterococcus, Porphyromonas, and Streptococcus species have been identified. Despite the high abundance of bacteriophage in the oral cavity, their role as critical determinants of bacterial population structure/ecology and virulence remains unknown.

Phages have been shown to play various roles in the host, such as influencing bacterial communities through predation, interacting with mammalian cells, and impacting the structure of biofilm communities. The ability of bacteriophage to penetrate biofilms has been shown to be more efficient than some antimicrobial treatments for biofilm removal, indicating that phages may serve as useful antibacterial agents in the oral cavity. Bacteriophages are strain specific and easy to isolate and manipulate, making them an ideal candidate to serve as a therapeutic that can disrupt unwanted biofilm. Bacteriophage could also be potentially engineered to release biofilm-degrading enzymes further enhancing biofilm breakdown. Phage therapy offers the benefit of not increasing  antibiotic resistance, and therefore could play an instrumental role in antimicrobial stewardship. In 2021, the Centers for Disease Control (CDC) reported that healthcare professionals prescribed over 211 million antibiotic prescriptions, 12% of which were prescribed by dentists. The overuse of antibiotic therapy leads to resistant bacterial strains that have become a serious health threat. In response to antibiotic resistance, researchers have revived interest in the use of bacteriophages as potential therapy. Although various Eastern European countries widely use phage-based treatments, there are no Food and Drug Administration (FDA)-approved phage therapies; use of phage therapy in the US is approved only under compassionate use conditions. The first U.S.-based clinical trial of phage therapy only recently began evaluating bacteriophage therapy against Pseudomonas aeruginosa in adults with cystic fibrosis who carry Pseudomonas aeruginosa in their lungs.

Specific Areas of Interest

Although increasing knowledge suggests that bacteriophages play important roles in regulating microbial ecosystems, bacteriophage-bacteria interactions in the human oral cavity remain less understood. Addressing this gap in knowledge around the role of phages in the oral environment will not only allow for an increased understanding of the ecology of the oral microbiome but may also provide potential novel therapeutics for the prevention and treatment of oral disease. Phage therapy is widely used in other countries, and with the start of the first U.S. clinical trial , it is an optimal time to expand studies on oral phage biology to support eventual development of therapeutics.

Much of the research on phage therapy in the oral cavity is in preliminary stages. While phages specific for numerous oral bacteria species have been identified and isolated, research is needed to increase our understanding of the roles and potential uses of bacteriophages in the oral cavity. Potential areas of research that could address current gaps in knowledge beyond identifying and characterizing new bacteriophages from the oral cavity include, but are not limited to, the following:

• Elucidating the roles of oral phages as drivers of bacterial diversity and dysbiosis in oral diseases
• Understanding the bacteriophage-bacterium relationship and effects on bacterial virulence, phage resistance, community structure, host physiology, and population dynamics
• Defining direct and indirect antibacterial properties and antibiofilm activity of phages
• Understanding phage-host interactions in vivo
• Developing basic tools to exploit phages as safe and effective modulators of oral microbial communities
• Examining the therapeutic potential of bacteriophages to prevent or treat oral diseases such as dental caries, gingivitis, and/or periodontal disease

Application and Submission Information

This notice applies to due dates on or after October 5, 2024 and subsequent receipt dates through January 8, 2028. 

Submit applications for this initiative using one of the following notice of funding opportunity (NOFO) or any reissues of these announcements through the expiration date of this NOSI. 

 All instructions in the SF424 (R&R) Application Guide and the NOFO used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-DE-24-014” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Tamara McNealy, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 202-430-1474
Email: tamara.mcnealy@nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Gabriel Hidalgo, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4630
Email:gabriel.hidalgo@nih.gov