Provide within the Chemical Biology Consortium (CBC) a cadre of members with the biological expertise and capability to rapidly develop sufficient information both in vitro and in vivo to determine the potential of novel discoveries, from the TCGA, NIH supported GWAS studies and TARGET projects, as well as basic NCI-supported discoveries, to be evaluated as potentially druggable therapeutic targets/diagnostics/biomarkers, etc. The first step will be to bring institutions into the CBC that have sufficient knowledge and the in house technical expertise to perform a thorough evaluation of molecular targets/pathways identified by these network anayses (TCGA?) as well as how amenable these targets might be to therapeutic intervention. These participants will initially be tasked with assessing the scientific merit of project proposals that are intended to eventually transition into the early discovery efforts of the CBC. The second step entails the development of experimental systems in which to interrogate the biology of the target and its associated pathways. These systems may include genetically manipulated cell lines and/or animal models that mimic defects observed in human cancers or will also be necessary to determine whether the necessary aspects of tumor biology can be recapitulated in these models. An additional level of interrogation would involve the perturbation of various combinations of genes to determine the number and specific combinations of relevant pathways necessary to model the diseased state. Expertise would be required in the generation of transgenic or knockout mice, the generation of stable cell lines expressing a gene of interest or translational inhibitors such as siRNAs or shRNAs for the functional ablation of targeted genes. Because such systems would then serve as the basis for high throughput screening assays or models for assessing the outcome of targeted medicinal chemistry efforts, members of the Functional Biology Working Space would also be required to work in an integrated fashion with CBC high-throughput screening and assay development centers to ensure that the biological reagents they develop will have utility in the development of molecularly-targeted anticancer agents. We envision potential contributors and advisors coming from Pharma, academia, and the NIH intramural research program (IRP).
