DESCRIPTION: A novel platform biotechnology, "natural products genomics" for seeking plant-based medicines has been developed which utilizes high throughput screening to identify active compounds in large populations of mutant plant cell cultures. This technology likely accesses the entire range of metabolic products of which the plant is capable. In this regard, plants, particularly their roots, are constantly under attack from bacterial and fungal pathogens that share similarities with those that infect the human oral cavity. The defense mechanisms of plants are therefore a potential source of antimicrobial compounds that may be of value in oral health. This application is to develop methods that will allow the novel platform technology to be applied to the identification and separation of plant compounds that are active against oral pathogens. For this, it is first necessary to develop an ultra high-throughput screen for antimicrobial activity that can be used with very small plant cell cultures. The development of this screen represents the deliverables for Phase I of this STTR. There are two major aspects to this development. First, appropriate pathogen cultures must be developed in which an indicator of cell damage/killing can be used to evaluate efficacy of plant culture secretions. Second, a mechanism for exposing the pathogen cultures to the mutant plant cell cultures must be developed. The application is to explore the possibility that pathogen and plant cultures can be grown on "matching" 96 well plates as co-culture systems, with plant cultures grown in wells with a semi-permeable membrane. The plates can then be placed in contact for 24h, with culture media separated only by the semi-permeable membrane, allowing secreted products from the cultures to diffuse onto the pathogens. If successful, this STTR will represent an extremely valuable transfer of the natural products genomics technology into the field of oral health medications. Compounds discovered by this method should be of considerable economic and medical value as proprietary medicines for the control of oral pathogens.