Project Summary Our understanding of the impact and workings of the innate immune system has increased exponentially in the past 25 years. Innate immunity is now a complex discipline that encompasses a variety of topics ranging from innate immune sensing and receptor signaling to microbial pathogenesis to auto-inflammatory and cardiovascular diseases. To effectively train students in such a cross-disciplinary field requires a cohesive and interactive faculty unit with diverse expertise. The 26 UMass Medical School faculty participating in Innate Immunity Training Program (IITP) represent just such a group. Our goal is to provide an outstanding training environment for predoctoral students committed to effectively and creatively expanding our understanding of innate immune mechanisms. This goal will be met by providing predoctoral trainees with: (1) a solid academic background in biochemistry/biophysics, molecular and cellular biology, immunology, and genetics through the UMMS core curriculum and IITP curricular components; (2) an in-depth understanding of rational experimental design as well as the subtleties of the innate immune system interactions through additional regularly scheduled journal clubs, seminar presentations by nationally/internationally recognized experts in the field, as well as by student and faculty IITP members; (3) an innovative, challenging and focused research experience using state of the art technologies; (4) opportunities to present research accomplishments at institutional, local, national and international forums; and (5) appropriate training in the ethical conduct of research. The diverse research interests of our faculty will provide trainees with a wide range of opportunities in both basic and translational research. Particular areas of faculty expertise include innate host defense mechanisms, pathogen evasion, pattern recognition receptor signaling and interactions (Toll-like receptors,NOD-like receptors, and beyond), complement cascades, inflammasome activation, innate-like lymphocyte subsets (B1 B-cells, iNKT cells), protein structure/function, and autoinflammatory diseases. We intend to support 6 predoctoral trainees (Ph.D or M.D./Ph.D. students) each year. Trainees will be selected based on their academic record and previous evidence of commitment to and talent for research. Special efforts will be made to recruit a diverse group of trainees. Training grant funds will enable our program to increase the caliber of student recruits and create an even more rigorous innate immunity research community.