This proposal describes a 5-year training program for the development of an academic career in infectious diseases (ID). The applicant has completed training in both pediatrics and ID. Her goal during the next 5 years is to develop the skills necessary to succeed as an independent scientific investigator in the fields of human immunology and cellular biology. The applicant's interest in ID prompted her research towards Mycobacterium tuberculosis (Mtb). This pathogen infects 1/3 of the world's population and is an enormous global burden. The CD8+ T cell response is increasingly recognized as important in the immune response against Mtb. Once internalized by cells, Mtb resides within a structure called the phagosome. Our preliminary data suggests that the phagosome may participate in MHC l-mediated """"""""cross-presentation"""""""" of Mtb-specific antigens to CD8+ T cells. The long-term goal is to investigate the role of the phagosome in Mtb infection.
The specific aims are: (1) Is the phagosome a MHC-I presenting organelle for Mtb? (2) Is the MHC-I molecule within the phagosome derived from the endoplasmic reticulum or recycled from the surface? Dr. David Lewinsohn will mentor the applicant's scientific development. Dr. Lewinsohn is a recognized leader in the field of human immunology against Mtb and has trained numerous postdoctoral fellows and graduate students. In addition, an advisory committee of highly-regarded medical scientists will provide scientific and career advice. The Pediatrics department at Oregon Health &Science University is a very collaborative environment and provides an ideal setting for training physician-scientists. The incorporation of expertise from diverse resources maximizes the potential for the applicant to establish a scientific basis from which an academic career can be founded. Relevance to public health: Mtb remains a significant contributor to morbidity and mortality worldwide. Our studies will advance knowledge in key areas of Mtb immunology, particularly regarding CD8+ T cells. Since a future vaccine against Mtb will likely need to include CD8+ T cell responses, our findings will guide the design and development of vaccine candidates. This proposal furthers the mission of the NIAID in determining better means of controlling Mtb, a pathogen with immense global impact.