Higher throughput scientific approaches can provide a foundation of enabling data that facilitates rapid and efficient progress in biomedical science. The discovery of chemical probes and proof-of-concept (POC) molecules provides enabling tools that remove a potential limiting factor in the progress of biomedical science and this can be achieved on occasion from high-throughput screening deliverables alone. The key hypothesis surrounding the development of the MLSCN proposal is that high throughput chemical approaches, when integrated with state-of-the art post-genome sequence, cell, molecular and in vivo biology, provides a rapid and facile mechanism for enhancing the progress of biomedical science. With the following proposal we intend to address the following aims:
Aim #1 : Establish a 96 well assay capable of being implemented in a 384-well format by the MLSCN Aim #2: Transfer the assay conditions and reagents to MLSCN for small molecule screening Aim #3: Provide selectivity screens for count-screening MLSCN hits RATIONALE Screening the NIH library to find POC molecules that act as agonists and antagonists for LPA1 receptor to study receptor function in vitro and the implication in the growth of neuronal cells and ovarian tumor migration. The goals of small molecule screening have been to provide useful chemical tools for the study of biological processes at molecular, cellular and in vivo levels. The success of the present process can be defined as the selection or identification of one or more selective, reasonably high affinity ligands for the proposed target. MATERIAL AND METHODS: Screening will be performed in a 96 or 384 well fluorescence imaging plate reader (FLIPR) format which allow throughput of >10,000 compound per day, screening throughput of 50-100,000 compounds per day can be achieved in homogenous assay formats. ? ?
