Summary Cancer affects the health of millions of Americans. Studying molecular mechanisms that endow cells with malignant properties is an essential component of advancing pre-clinical studies and a key part of efforts to improve patient outcomes. The purpose of this COBRE submission is to establish the Center for Molecular Interactions in Cancer (CMIC) at the University of Arkansas for Medical Sciences (UAMS). The mission of the CMIC is to study molecular features and functional properties of biomolecules that drive cancer. The unifying theme of research among Center members is the coupling of structural biology and high-resolution imaging with precise, quantitative analysis of biochemical and cellular processes to understand how molecular interactions govern the initiation, progression and treatment of cancer. In Phase 1 of this COBRE, we will pursue the following aims: (Aim 1) establish the CMICcreating an organizational framework that ensures the success of junior investigators as independent scientists and strengthens the research infrastructure at UAMS and its affiliate institutions, (Aim 2) build a thematic, multidisciplinary COBRE center with unique collaborative opportunities and strong research programs focused on understanding the molecular basis of cancer, and (Aim 3) implement a plan for long-term sustainability of the CMIC. The organization of the CMIC will include 5 Research Projects, an Administrative Core, and 2 new research coresthe Structural Biology Core and the Biomolecular Interactions Core. The Administrative Core will oversee operation of the Center, including a Pilot Project Program to fuel the pipeline of replacement Research Project Leaders (RPLs) and a formalized Faculty Development Plan that includes individualized mentoring. The Structural Biology Core will help RPLs plan and execute structure-function studies by ensuring high-quality sample preparation and providing access to world-class instrumentation and computational resources required for high-resolution structural studies. The Biomolecular Interactions Core will enable researchers to perform quantitative analysis of macromolecular interactions and dynamics down to the level of single-molecules. Both research cores will assist users in experimental design, data analysis and interpretation of results, while also providing training and educational outreach. The CMIC will address an institutional priority at UAMS and contribute to the mission of the Winthrop P. Rockefeller Cancer Institute by creating a critical mass of investigators who are able to gain molecular-level insights into mechanisms that are crucial for a deep understanding of cancer biology. Our long-term goal is to leverage faculty mentoring, strategic recruitment, and cutting-edge core resources to develop a critical mass of investigators that will support a self- sustaining center in which research advances our knowledge of cancer through precise and comprehensive analyses of molecular events tha...