PROJECT SUMMARY – Administrative Core This Combating Antibiotic Resistant Bacteria (CARB) proposal outlines the design and function of a multidisciplinary, collaborative partnership applying new and innovative approaches to understand the mechanisms underlying bacterial envelope assembly and enable the discovery of treatments against multidrug- resistant infections. Because this is an academic effort, emphasis will be on developing the scientific knowledge that will allow discovery of new compounds and protein therapeutics for especially challenging and unexploited targets involved in cell envelope biogenesis, with membrane proteins and protein complexes a focal point in all three projects. The project team comprises an accomplished group of scientists with extensive and synergistic expertise in biochemistry, including reconstitutions of multi-enzyme pathways and large protein machines, in structural biology of membrane proteins and membrane protein complexes, in approaches for discovery of components essential for cell envelope biogenesis, in the creative use of genetic screens to dissect the regulation of pathways important in cell division and envelope biogenesis, and in development of new technologies and screening approaches for discovery of antimicrobial compounds and therapeutic proteins. Synergistic expertise in both the Gram-negative and Gram-positive cell envelopes is also well-represented among the project team members. The scientific expertise of the project team will be complemented by substantial administrative experience. The goal of the CARB Administrative Core therefore is to oversee the smooth implementation of the research plan and deployment of resources, and to foster the cohesive and well- functioning whole to achieve goals that are greater than the sum of the individual projects. This will be accomplished by achieving the following Specific Aims: 1) Provide program management, oversight, and compliance assurance, 2) Facilitate regular interactions among CARB investigators and trainees from the various labs and projects in a smooth and effective manner, and promote connectivity with other Harvard-wide initiatives; 3) Provide critical infrastructure for fiscal management of the program; 4) Provide a single point of contact and active coordination for on-going communication with NIAID, the Program Officer, and other NIAID staff and initiatives. The Administrative Core will foster the continued development of a highly functioning, well integrated, and synergistic whole to contribute to much-needed scientific advances in a challenging area of research that holds considerable promise for overcoming antibiotic resistance, while generating resources and fostering data sharing with the greater scientific community.