Project summary/Abstract Research: To discover novel factors and mechanisms that enhance the quality of memory T cells has the potential to impact the development of cancer immunotherapies. My recent publication demonstrated that caloric restriction (CR) enhanced the function of memory T cells to control melanoma and significantly extend host survival. As such, CR could represent an accessible nutritional intervention to modulate the function of the immune system for the treatment of cancer. However, the molecular determinants and signalling pathways involved remain unclear, which are critical to uncover in order to rationally design and implement diet-based therapeutic approaches. Based on preliminary data and the published work of others, this proposal will investigate the role of microbiota-derived acetate in enhancing memory T cell function during CR to promote melanoma control. Such information has the potential to benefit human health by improving strategies aimed at treating cancer. Career Goals: My overarching career goal is to become an independent investigator at an academic institution where I study the mechanisms by which CR can be utilized as a nutritional intervention to modulate the immune system for the treatment cancer. Furthermore, I believe that teaching and mentoring are essential aspects of being an independent investigator and therefore aspire to become an inspirational teacher and an outstanding mentor. Career Development Plan: To become a successful independent investigator I will need to develop various research, professional and personal skills. These will include acquiring expertise in molecular biology and microbiology techniques, as well as fostering collaborations and developing skills in writing, mentoring, teaching, communicating and laboratory management. The NIH provides an outstanding academic environment in which trainees can fulfil these criteria by regularly presenting data, receiving feedback from prominent scientists, fostering collaborations and enrolling in courses to develop skills in specialist scientific areas, personal development and laboratory management. Furthermore, in addition to my mentor and co-mentor, I have support from several independent investigators with extensive expertise in areas that will greatly facilitate the completion of experiments proposed here. As such, the NIH is an ideal environment to develop during the K99 phase as I progress to become a successful independent investigator. Career Development Environment: I will perform the K99 phase in the laboratory of Dr. Yasmine Belkaid at the NIH, which provides an unprecedented environment in terms of the resources and facilities available. The laboratory has access to all of the instruments and facilities necessary to complete the experiments proposed in this application. These include a gnotobiotic animal facility and a sequencing facility that also provides bioinformatics analysis. The mentorship I will receive will be of the highe...