Project Summary This is a resubmission of a new competitive proposal for an NHLBI T32 training grant. Sleep/wake and circadian rhythms involve state changes of multisystem biological function that may not in themselves be vital to life but the systems under this modulatory control are vital to life. Further, optimal function of these systems, required for healthy living, is severely compromised in the absence of these intricately organized state changes. The regular and/or rhythmic occurrence of state changes is evolutionarily preserved and adverse outcomes in a variety of organ systems, including CNS, cardiovascular, respiratory, immune, and metabolic systems are associated with their disruption. However, the mechanisms, the mechanisms’ integration and both qualitative and quantitative impact of the state-change related modulation and overall health of the organism (including humans) is not well understood. An overall goal of this T32 proposal is to prepare a group of pre-doctoral and post-doctoral researchers to engage in the challenging endeavor of effective investigation to help remedy this vitally important gap in our biological understanding. Not only will the trainees receive in depth exposure and experience in effective application of multiple and integrated state of the art technologies and experimental approaches from world leaders, but additionally, strong integrative and collaborative interaction and facilitation of this interaction will be generated from our proposed structure within the newly developed Peter O’Donnell Brain Institute. This will enhance the trainee’s ability to engage in independent development of successful research programs that truly span the usual gulf from bench to bedside in a manner that integrates multiple biological systems across behavioral states as demanded by effective sleep/wake and circadian research. Finally, trainees will receive mentored experience in grant writing and in the communication and publication of integrative form of research and career counseling to enabling successful pursuit of a sleep and circadian research oriented career.