Project Summary: Overall The goal of the Nebraska Center for Molecular Target Discovery and Development (CMTDD) is to establish and expand physical and intellectual resources at the University of Nebraska Medical Center (UNMC) and the University of Nebraska system to catalyze the identification, validation, and development of approaches for manipulation of molecular targets implicated in clinically important diseases. We perceive an increasing expectation by journals and granting agencies for progressively sophisticated model systems and data sets. Acquisition of these systems and generation of high-content data often requires a substantial investment in time and money that taxes limited research resources. To enhance the competitiveness of CMTDD Research Project Leaders (RPLs) and other university faculty members during Phase 2, the CMTDD recently invested in the development of technologies to enhance the sophistication of investigator research while minimizing the cost of access. These technologies: single-cell and spatial transcriptomic analysis, organoid generation and manipulation, and inhibitor and proteolysis-targeting chimera (PROTAC) synthesis will be integrated into three Phase 2 CMTDD cores. These investments will enhance the research capabilities of the institution, expand the translational capacity of its faculty, facilitate the training, mentoring, and career advancement of promising new faculty, and efficiently drive discovery and development for the improvement of human health in Nebraska and the nation. Phase 2 RPLs bring a breadth of cutting-edge expertise to the CMTDD. With mentoring and ready access to CMTDD-supported cores, our RPLs will become self-supporting faculty members invaluable to the future success of UNMC. Our Phase 2 RPLs share both a passion for exploration of the basic biologic principles that underly cell homeostasis and a belief that many diseases can be effectively classified and characterized through detailed genomic, genetic, and molecular analyses that identify drivers and vulnerabilities from which will emerge unique therapeutic approaches. To realize this vision, the CMTDD will: 1) maintain an Administrative Core and mentoring program that successfully graduated all but one of its initial RPLs in the first four years of support; 2) increase research capacity through newly established state-of-the-art scientific cores for single-cell and spatial transcriptomics, organoid development, and inhibitor and PROTAC synthesis and validation; and 3) provide low- or no-cost access to these technologies and reagents as an affordable means for increasing the impact of investigator research.

Project Narrative: Overall Impactful biomedical research requires an increasing level of sophistication in data acquisition and analysis. The goal of the Nebraska Center for Molecular Target Discovery and Development is to facilitate biomedical research university-wide by providing mentoring/guidance and underwriting the cost of access to cutting-edge techniques that will catalyze the identification, validation, and development of potential therapies against molecular targets for clinically important diseases.