The proposed NIDCR Dentist Scientist Pathway to Independence Award (K99/R00) will provide me advanced
research and academic training to become an independent dentist-scientist at the interface of oral microbiology,
biophysics, and spatial omics with impact in Early Childhood Caries (ECC). ECC is a major public health problem
characterized by high microbial carriage forming intractable plaque-biofilms on teeth exposed to sugar-laden
dietary habits. The disease leads to rampant tooth-decay, is costly to treat and can cause systemic complications
in children. Previous studies and a recent multi-omics analysis of dental plaque from two large community-based
cohorts of pre-school children (>400) have identified Selenomonas sputigena (Ss), a motile bacterium, to be
strongly associated with ECC. This finding was further validated in an in vivo caries model whereby Ss
exacerbated the severity of carious lesions when co-infected with Streptococcus mutans (Sm). However, the
role of Ss and its motility on biofilm formation, interspecies interaction with Sm, and cariogenic functions are
unknown. To address this, I will focus on the overall hypothesis that the motile Ss colonizes tooth surface and
interacts with Sm to mediate biofilm spatial structuring and community functions that promote emergent caries-
causing properties of supragingival biofilms through three Aims: (1) Characterize Ss motility on surface
colonization and biofilm initiation; (2) Determine the dynamics of biofilm assembly, spatial transcriptomics and
disease-associated functions; (3) Investigate Ss-mediated colonization, interspecies spatial structuring/omics
and biofilm virulence in vivo. The outcome will elucidate the role of Ss and its motility in supragingival biofilm
formation and Ss contributions to the etiopathogenesis of ECC. During the K99 mentored phase, I will conduct
research in the lab of my primary mentor/co-mentor, while developing key expertise in 3 areas: 1) advanced
skills in biophysical methods to study motile bacteria; 2) acquiring knowledge and technical skills in single-cell
RNA sequencing and spatial transcriptomics; 3) improving scientific communication and grant writing skills. In
addition, I will incorporate mentoring and laboratory managing skills as well as networking. In transition to
independent R00 phase, I will implement and complete the spatial transcriptomics studies to understand how
Ss influence biofilm interspecies interactions and determine its pathogenic role in dental caries in vivo. The data
will provide ample opportunities for further mechanistic studies and targeted strategies for ECC. In addition, it
will provide a platform to study other motile oral bacteria in health and disease, which remain understudied.
Collectively, the proposal will broaden my vision and skills by capitalizing on highly experienced mentor and co-
mentor with an interdisciplinary advisory committee with complementary expertise in biophysics, spatial multi-
omics, oral microbiome, and clinical research. I will gain essential knowledge, skills, and experience to build my
own research program with the goal of receiving an R01 prior to the end of award, and successfully guide me to
pursue independent dentist-scientist career in oral microbiology and cariology with multidisciplinary vision.