PROJECT SUMMARY The Synthetic Chemical Biology Core (SCBC) was established in July 2016 from the merger of the Center for Molecular Analysis of Disease Pathways (CMADP) Molecular Probes Core (MPC) with the newly established Chemical Biology of Infectious Disease (CBID) Medicinal Chemistry Core (MCC). The synthetic capabilities of the SCBC will fulfill the specific aims of both COBRE centers. The mission for the SCBC in Phase II is to provide the junior faculty affiliated with CMADP, as well as other investigators in the state of Kansas, with novel molecular probes of biological systems. The SCBC will also offer the capability to evaluate these probes in vitro in whole- cell bioassays, and in vivo in zebrafish, an increasingly important model organism for biomedical research. The SCBC will also fulfill CBID?s missions concerning anti-infective drug discovery. These projects will be funded through the CBID. The SCBC Director is responsible for coordinating all SCBC Core lab activities to both COBRE centers. The SCBC will offer expert design of molecular probes and synthesis of both small molecules and peptides, with an emphasis on the generation of fluorescent and other tagged molecules. SCBC will also offer bioassays of molecular probes, including whole cell assays and assays using zebrafish, to bridge a gap that currently exists between very high resolution imaging of cells in culture and low resolution imaging of fluorescent tracers in rodents. The newly established SCBC would function synergistically with other CMADP-funded Core facilities, including the Genome Sequencing Core, to identify genes that impact functions of probes in vivo, and the Microfabrication and Microfluidics Core, to develop devices for imaging and chemical analysis. This integration is designed to empower faculty to use chemical biology approaches to investigate biological problems. The SCBC provides investigators with access to highly qualified personnel with experience in synthetic organic chemistry, biochemistry, microscopy, and approaches for optimization of biological properties of synthetic molecules. The Center has two Co-Core Leaders from the Department of Medicinal Chemistry at KU. Prof. Blake Peterson will continue to be the Leader of the CMADP?s part of the SCBC. Prof. Tom Prisinzano is the Leader of the CBID part of the SCBC. The Director of SCBC is Dr. Chamani Perera. The specific aims that will be addressed by the SCBC for this Phase II proposal are: (1) to continue to integrate resources from the proposed COBRE Center for Molecular Analysis of Disease Pathways Phase II with the existing COBRE Center for Chemical Biology of Infectious Disease Phase I to further establish the new SCBC, gain economies of scale, and serve faculty affiliated with the COBRE CMADP; (2) design and synthesize molecular probes of biological systems for faculty investigators; (3) enable faculty clients to conduct bioassays in cell culture and zebrafish models; and (4) provide outreach and administrative support necessary to manage Core activities, and offer services to the larger biomedical research community in the state of Kansas.