Project Grant R00DE029527
- The National Institute of Dental and Craniofacial Research (NIDCR) awarded a $310,500 Project Grant under the Oral Diseases and Disorders Research program (CFDA 93.121) to Virginia Commonwealth University (VCU) to conduct comparative experimental evolution research on gene essentiality in the oral bacteria Streptococcus sanguinis and S. mutans. The research aims to enhance understanding of how differences in essential genes contribute to the contrasting roles these bacteria play in oral health...
- This Project Grant award from the National Institute of Dental and Craniofacial Research (NIDCR), under the Oral Diseases and Disorders Research program (CFDA 93.121), will provide $460,885 to The Trustees of the University of Pennsylvania to investigate how the interaction between the fungus Candida albicans and the bacteria Streptococcus mutans leads to the initiation and progression of severe early-childhood caries (S-ECC). The research aims to understand how this interkingdom microbial...
- This federal Project Grant award of $597,807.00 from the National Institute of Dental and Craniofacial Research (NIDCR), under the Oral Diseases and Disorders Research program (CFDA 93.121), will establish a novel 13C-labeled metabolite library for the study of dental caries. The key objectives are to: Create a 13C-labeled oral bacterial metabolite reference library for Streptococcus mutans and Streptococcus gordonii using SWATH LC-MS, with dual peaks identified and curated to improve rigor...
- This Project Grant award from the National Institute of Dental and Craniofacial Research (NIDCR), under the Oral Diseases and Disorders Research federal grant program (CFDA 93.121), provides $241,500.00 to support research focused on identifying diffusible small molecules that regulate the replication of the oral bacterium Porphyromonas gingivalis (Pg). The goal is to elucidate the mechanisms by which Pg, a late-stage colonizer linked to periodontitis and other systemic conditions, overcomes...
- This Project Grant award of $470,279 from the National Institute of Dental and Craniofacial Research (NIDCR), under the Oral Diseases and Disorders Research program (CFDA 93.121), aims to study the impact of bacterial oxidative stress responses on the ecology and pathogenicity of oral streptococci. The research project, conducted at the University of Alabama at Birmingham (UAB), will identify and characterize the hypochlorous acid (HOSCN) response mechanisms in oral streptococci, particularly...
- This federal Project Grant award of $163,411 from the National Institute of Dental and Craniofacial Research (NIDCR), under the Oral Diseases and Disorders Research federal grant program (CFDA 93.121), supports research to characterize the nutritional niches and interactions between Streptococcus mutans, a primary driver of dental caries, and other commensal oral streptococci species. The research aims to understand how these microcolony biofilm structures form, the interactions between S....
- The National Institute of Dental and Craniofacial Research (NIDCR) awarded a $205,000 Project Grant under the Oral Diseases and Disorders Research program (CFDA 93.121) to The Regents of the University of California, San Francisco (UCSF). The award, effective April 8, 2025 through March 31, 2027, will support research to determine the relationship between the oral microbiome, dental caries, and adverse outcomes in pediatric hematopoietic cell transplant recipients. The study aims to identify how...
- The National Institute of Dental and Craniofacial Research (NIDCR) awarded a $620,000 Project Grant under the Oral Diseases and Disorders Research (CFDA 93.121) program to the Regents of the University of Minnesota, Office of Sponsored Projects Administration. The grant will fund research to identify natural products synthesized by Streptococcus mutans bacteria that have antibacterial and antibiofilm activity against the oral pathogen Enterococcus faecalis. The research aims to determine how...
- The University of Kansas Center for Research Inc. was awarded a $467,008 Project Grant from the National Institute of Dental and Craniofacial Research (NIDCR), under the Oral Diseases and Disorders Research program (CFDA 93.121), to develop a novel non-invasive treatment for dental caries in children and patients with special needs. The project aims to create a biomimetic peptide-polymer interface that works synergistically with silver diamine fluoride (SDF) to arrest caries progression and...
- This federal Project Grant award of $645,988 from the National Institute of Dental and Craniofacial Research (NIDCR) under the Oral Diseases and Disorders Research (CFDA 93.121) program supports research on the role of bacteriophages (phages) in the development of dental caries. The multi-year project aims to leverage advanced computational platforms to characterize the oral phageome and understand how phage dynamics impact the microbial shifts that lead to early childhood caries. Key objectives...
NOVEL SMALL MOLECULE BIOSYNTHETIC GENE CLUSTERS IN STREPTOCOCCUS MUTANS AND VIRULENCE OF DENTAL CARIES - PROJECT SUMMARY DENTAL CARIES IS A GLOBAL INFECTIOUS DISEASE IMPACTING THE LIVES OF 80% OF THE HUMAN POPULATION. SEVERE EARLY CHILDHOOD CARIES (SECC) IS OF PARTICULAR CONCERN AND CHARACTERIZED BY EXTENSIVE TOOTH DECAY THAT CAN DRAMATICALLY AFFECT THE DENTAL HEALTH OF CHILDREN UNDER SIX YEARS OF AGE. THIS CONSTITUTES A SIGNIFICANT ECONOMIC BURDEN, CAN HAVE DRAMATIC IMPACT ON THE CHILD'S WELL BEING AND MAY CONTRIBUTE TO OVERALL HEALTH LATER IN LIFE. STREPTOCOCCUS MUTANS IS THE BACTERIUM MOST COMMONLY ASSOCIATED WITH INITIATION OF SECC AND EARLY CHILDHOOD CARIES (ECC). BIOSYNTHETIC GENE CLUSTERS (BGCS) IN BACTERIA OFTEN ENCODE GENES FOR SMALL MOLECULES AND OTHER ANTIMICROBIAL PEPTIDES. THIS RESEARCH PLAN PROPOSES TO INVESTIGATE A NOVEL BGC (BUTYROLACTONE-LADDERANE HYBRID, BL-BGC) OF S. MUTANS FROM A HIGH CARIES RISK POPULATION TO IDENTIFY ITS IMPACT ON S. MUTANS VIRULENCE AND SURVIVAL TRAITS. PRELIMINARY DATA SUGGESTS THE BL-BGC IS SIGNIFICANTLY UP REGULATED IN DENTAL CARIES AND OCCURS IN THE MOST PREVALENT STRAIN TYPE OF S. MUTANS WITHIN A HIGH-CARIES RISK STUDY POPULATION. THE HYPOTHESIS IS THAT CLINICAL S. MUTANS STRAINS WITH THE BL-BGC WILL HAVE INCREASED VIRULENCE PROPERTIES AND CARIOGENICITY. AIM 1 WILL CHARACTERIZE PHENOTYPES OF CLINICAL S. MUTANS STRAINS CONTAINING THE BL- BGC AND THEIR ASSOCIATION WITH DENTAL CARIES KEY VIRULENCE AND SURVIVAL TRAITS USING GENE MUTAGENESIS AND IN-VIVO BIOFILM ANALYSIS. AIM 2 WILL DETERMINE THE IMPACT OF BL-BGC ON EXPRESSION OF VIRULENCE GENES AND METABOLITES IN S. MUTANS BIOFILMS USING RNA-SEQUENCING AND METABOLOMICS ANALYSIS. AIM 3 WILL DETERMINE THE HOW BL-BGC IMPACTS S. MUTANS COLONIZATION AND VIRULENCE USING ANIMAL MODELS OF DENTAL CARIES. THE PROPOSED STUDY WILL ELUCIDATE THE ROLE OF BL-BGC IN S. MUTANS VIRULENCE AND FITNESS DURING THE K99 PHASE. METABOLITES PRODUCED BY S. MUTANS WITH BL-BGC IMPACTING KEY VIRULENCE TRAITS WILL BE PURIFIED AND CHARACTERIZED IN THE R00 PHASE, PROVIDING NEW INSIGHTS INTO S. MUTANS' ROLE IN THE PATHOGENESIS OF DENTAL CARIES. CHARACTERIZATION OF THIS AND OTHER BGCS MAY LEAD TO NEW THERAPEUTIC TARGETS DESIGNED TO REDUCE, REVERSE, OR EVEN PREVENT SECC. THE K99 PHASE OF THIS AWARD WILL PROVIDE THE TIME AND SUPPORT FOR ADDITIONAL RESEARCH TRAINING, BUILDING EFFECTIVE COLLABORATIONS, ENHANCING PROFESSIONAL DEVELOPMENT AND SUBMISSION OF PUBLICATIONS LEADING TO A SUCCESSFUL TRANSITION TO AN INDEPENDENT ACADEMIC RESEARCH APPOINTMENT IN THE R00 PHASE. THIS STUDY IS UNIQUE IN THE USE OF BGCS FROM CLINICAL S. MUTANS ISOLATES FROM A HIGH-RISK CARIES POPULATION ALLOWING FOR CLINICAL TRANSLATION OF RESULTS AND THE USE OF METABOLOMICS FOR IDENTIFICATION OF BL-BGC RELATED COMPOUNDS/METABOLITES. THIS STUDY WILL ENABLE AN INDEPENDENT CAREER PATH BY ESTABLISHING A MULTIDISCIPLINARY PROGRAM UTILIZING MOLECULAR BIOLOGY APPROACHES TO VALIDATE EPIDEMIOLOGICAL ASSOCIATIONS, BRIDGING THESE FIELDS AND ADVANCING THE KNOWLEDGE OF S. MUTANS VIRULENCE IN CARIES.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $249.0k | 3/20/25 | ||
| Not listed | $248.5k | 5/17/24 | ||
| Not listed | $248.5k | 5/17/24 |