The complex microbial communities that reside in the oral cavity are now accepted to play important roles in host health and disease. During the last 60 years of research the major focus of oral microbial ecology has been on single and dual species interactions. Even though a few studies include up to 10 species they are far from being representative of the human oral cavity that harbors approximately 700 bacterial species. Earlier studies show that nutritional factors especially carbohydrate intake and nitrogen sources greatly affect oral bacterial growth and their associations with health/disease. However, our understanding of these interactions at a community level is very limited and it is unclear to what extent we can translate the knowledge from studies of only a few species into a community context. This proposal seeks to understand how bacterial gene expression and signaling molecules orchestrate the development of both health and caries associated communities through dissection of transcriptional and metabolite networks that controls these processes. The ultimate goal is to understand how key metabolic interactions at low-pH contribute to the ecologically and clinically important properties of oral biofilms, such as selection for cariogenic bacteria, pH recovery in health associated communities, and cell-cell communication. The candidate, Dr. Edlund, has a longstanding interest and history in studying bacterial ecological functions in the environment and therefore, ecology studies of oral communities is a logical extension of her research. Her career trajectory after the mentored phase of this K99 is to become an assistant professor at a leading academic research institute, where she hopes to continue and further her research program on oral biofilms, perform teaching responsibilities, and train future scientists. Dr. Edlund believes that in the long-term, once more is known about how oral biofilms are regulated, her findings will provide important information to developing new drugs to treat and prevent oral diseases. This K99/R00 proposal is designed to complement Dr. Edlund's prior research experience and to provide her with substantive and necessary technical and intellectual expertise as well as the confidence to function as an independent investigator. The candidate will receive her K99 training at the renowned institution UCLA, which will put her in a prime position to move on to similarly ranked Universities. Dr. Edlund's choices of primary mentor, Dr. Shi, and co-mentors, Dr. Dorrestein and Dr. McLean were carefully selected for their relevant, diverse, and complementary expertise to cover all elements of her proposal. In addition, Dr. Edlund has assembled an advisory committee consisting of a diverse group of basic scientists and physicians to oversee her scientific progression and career development throughout her transition to becoming an independent investigator.
Caries disease is a result from acid formation in dental plaque and is a global health problem causing detrimental effects on people's health and overall life quality. This proposal seeks to understand key molecular mechanisms underlying the transition from a highly diverse and healthy oral microbiome to a disease- associated microbiome by using an in vitro biofilm model system, capable of supporting growth of more than 150 oral bacterial species. Understanding the molecular dynamics of oral biofilms and their responses to carbohydrates in more detail will lead to improvements in preventing and treating caries infection.