Developing a Chiropteran model to study the impact of thermal stress on antiviral immunity and inflammatory responses

PROJECT SUMMARY/ABSTRACT The purpose of the proposed Career Development Award (K01 SERCA) is to provide Dr. Anna Fagre with protected time and collaborative mentorship so that she can build a strong foundation for her career as an independent investigator. Dr. Fagre's proposed K01 career development training plan builds on >7 years of experience studying bats (order Chiroptera), arthropod vectors, and arboviruses in both the field and the lab. Importantly, it integrates additional training in three focus areas: (1) development of atypical animal models for complex studies involving host-arbovirus-vector interactions, (2) advanced training in multi- omics analysis, and (3) application of comparative approaches in immunology and stress physiology to Chiropteran models of infection and disease. Dr. Fagre's proposed K01 research outlines the development of a bat model to characterize the impacts of thermal stress on host-arbovirus-vector interactions, incorporating novel datalogging technologies to minimize animal handling while leveraging methodologies used in the fields of stress physiology and environmental health. Dr. Fagre will explore these questions with 3 specific aims: (1) development of a Chiropteran model for assessing innate immunity and inflammasome activation in bats exposed to thermal stress, (2) characterization of ambient temperature's impact on host-vector interactions in bats following subdermal inoculation with mosquito salivary gland extract, and (3) quantification of ZIKV infection dynamics and host responses at different temperatures in cell lines derived from taxonomically diverse bat species. The anticipated results will contribute to ecoimmunology and ecophysiology studies by expanding our knowledge of how heat stress affects bat immunology and host-virus interactions. In leading these studies, Dr. Fagre will be uniquely poised to build out an independent research program interrogating the transmission dynamics of emerging arboviruses, harnessing a combination of in vivo and in vitro methods supplemented with field-based studies leveraging her past epidemiologic training. Not only will the proposed aims build a framework within which to characterize the impact of environmental stress on host-virus-vector interactions and viral infection outcomes, but results will aid in the identification of valuable diagnostic biomarkers for heat stress and viral infection. The K01 SERCA award would provide Dr. Fagre with continued funding and dedicated time to strengthen her research portfolio and build her own research program before applying for tenure-track faculty positions.