PROJECT SUMMARY/ABSTRACT The purpose of this NIH F31-Diversity application is to obtain support for the PI, Kristin Olson, for mentored research and career development activities within her MD/PhD degree training that will strengthen her potential to become a successful physician scientist. The project goal is to develop skills in statistical genetics that will allow the PI to study the influence of immunogenetic determinants on Chlamydia trachomatis (CT) infection outcomes in women, including methods of genetic data quality control, imputation, multiple testing corrections, and pathway analyses. The primary objective of the research proposal is to investigate the immunogenetic determinants of Chlamydia trachomatis (CT) reinfection and CT-associated infertility in women. CT infection is the most prevalent sexually transmitted bacterial infection worldwide, including in the U.S. CT disproportionately affects women due to the reproductive morbidity it causes. Up to 20% of women experience reinfection after treatment and inflammation from repeated CT infection episodes can contribute to risk for CT- associated infertility. It is unknown why some women remain susceptible to CT after treatment, leading to reinfection, and why some CT infections lead to infertility. This project seeks to determine genetic risk markers for CT reinfection and CT-related infertility (Aims 1A and 2A), and then utilize complex statistical methods to predict the immune responses mediated by these genetic markers (Aims 1B and 2B). The central hypothesis is that genetic factors influence risk for these CT infection outcomes through specific immunological pathways, and some genetic factors may contribute to both clinical outcomes while others may be unique for only one of the clinical outcomes. The long-term objective of our research is to understand immunogenetic factors that influence CT infection outcomes in order to develop strategies for improving prevention and management of CT infection, such as optimizing chlamydia screening strategies and development of a chlamydia vaccine. The proposed training plan for the PI is sponsored by her project co-mentors, Dr. William Geisler and Dr. Hemant Tiwari. Included in the training plan are experiences that help the PI develop in three major areas: 1) rigorous research in the CT field, including developing familiarity with the existing CT literature, critically evaluating published CT studies, principles of scientific integrity and responsible conduct of research, and methods of rigor and reproducibility; 2) statistical genetics, including methodology and interpretation of results; and 3) career and professional development, including learning skills in grant writing, journal reviewing, presenting, and translation of research findings to clinical applications. The overall goal of the training plan is to provide the PI with a solid foundation for a successful career as a physician scientist, with the ultimate career goal of leading a collaborative research team that bridges the gap between laboratory-based research and systems-based research in the context of improving reproductive health outcomes for women.

PROJECT NARRATIVE Chlamydia trachomatis (CT) infection, the most prevalent sexually transmitted bacterial infection worldwide, is one of the most common causes of female infertility. It remains unclear why some women remain susceptible to CT reinfection after treatment and why some women develop infertility after CT infection. In this project, I am investigating the genetic determinants that predict risk for CT reinfection and CT-associated infertility and utilizing statistical methods to further predict immunological pathways mediated by these genetic determinants in order to guide and develop strategies for the prevention of CT infection.