PROJECT SUMMARY/ABSTRACT Regulation of biomolecular communication pathways is critical to maintaining physiological function. Unraveling these pathways and filling in critical knowledge gaps will provide novel opportunities to understand, diagnose, and treat human diseases. During Phase 1, the Nebraska Center for Integrated Biomolecular Communication (CIBC) supported 15 early stage investigators (ESIs), helped recruit four new faculty members to the University of Nebraska-Lincoln (UNL), and established two research cores. CIBC’s ESIs secured $16.7 million in external research funds and authored 82 peer-reviewed publications. Building on Phase 1, the goal of the CIBC in Phase 2 is to continue building a critical mass of biomedical investigators and supporting research infrastructure in the area of biomolecular communication pathways at UNL that will position CIBC for a successful transition to long- term sustainability in Phase 3. CIBC will continue to develop multidisciplinary teams to interrogate complex disease pathways, especially by connecting researchers developing new molecular probes and analytical techniques with those unravelling molecular mechanisms of human diseases. CIBC’s Phase 2 specific aims are to: 1) strengthen UNL’s biomedical research infrastructure by supporting the research efforts and career development of biomedical investigators whose research is broadly focused on understanding the regulation of biomedically relevant communication pathways; 2) enhance research capabilities by maintaining and expanding the Systems Biology Core (SBC) to facilitate acquisition of essential bioanalytical data and the Data and Life Sciences Core (DLSC) to provide critical bioinformatics support and data management, storage, and sharing to Center members; and 3) advance interdisciplinary research collaborations with broad disciplinary representation to pursue high-impact research into complex disease from diverse perspectives. The initial Phase 2 Project Leaders will pursue projects interrelated by their fundamental focus on different aspects of the biomolecular basis of disease-associated communication pathways. These projects, which signify CIBC’s interdisciplinary nature, are directed toward: 1) developing novel chemical probes and targeted mass spectrometry approaches to study the cocaine and amphetamine-regulated transcript peptide and receptor(s), 2) understanding how the 7SK RNP regulates transcription and its implications in human diseases, 3) conducting near real-time detection of methicillin-resistant S. aureus by developing a generalizable electrochemical peptide-based biosensing platform, and 4) developing a novel Unnatural Amino Acid-based Chromatin Isolation Method (UChIMe) with improved accuracy and sensitivity. CIBC will further expand SBC and DLSC to enable Nebraska’s biomedical researchers to pursue high-impact biomedical research. CIBC’s innovation is in integrating the research activities of chemists, biochemists, engineers, and bioinformaticians to understand how cells communicate and integrate metabolic and regulatory pathways relevant to disease development and progression.

PROJECT NARRATIVE Diseases result when the internal stability and normal communications within and among biological pathways are disrupted by genetic defects, environmental disturbances, or pathogens. The Nebraska Center for Integrated Biomolecular Communication (CIBC) integrates the research activities of chemists, biochemists, engineers, and bioinformaticians to address critical knowledge gaps in our understanding of how cells communicate and integrate metabolic and regulatory pathways relevant to complex disease development and progression. CIBC investigators will continue to bring together unique expertise in the understanding of complex diseases and in the development of novel methodologies and technologies to probe communication pathways. 1