PROJECT 3
Project 3 seeks to translate the scientific findings of this Program Project into new prevention strategies that could be utilized to reduce the incidence of tick-borne diseases. Our past studies contributed to a deeper understanding of tick biology, particularly revealing that tick signaling pathways (JAK/STAT and IMD) modulate tick immune responses and developmental processes, and that specific tick proteins (such as ISARL, which is involved in metabolism, and the secreted protein IsC1ql3) facilitate the survival of B. burgdorferi within the tick or its transmission to hosts. Led by the PI, Dr. Erol Fikrig, the team at Yale University will investigate whether proteins that promote critical aspects of tick development, metabolism, and immunity could serve as novel targets for anti-tick measures, as their interference could impair the life cycles of the tick and the pathogens they harbor.
Building on previous mechanistic findings from the Tick Immunity project, and incorporating newer observations from the ongoing Project 1 and Project 2 studies, the Project 3 efforts will evaluate whether the targeting of key domains or secreted components of the tick immune and metabolic pathways can induce protective immunity in the host. The project also addresses how the targeting and impairment of these key domains or secreted components can interfere with the tick life cycle, pathogen survival, and pathogen transmission. These results will provide the basis for understanding how tick immune-developmental and metabolic pathways may be targeted to impair the tick-pathogen cycle, which could be utilized in future work to develop host-targeted preventive measures to control infection and tick populations.
Specific Aims
Tick immune-developmental and metabolic pathways as anti-tick vaccine targets
Aim 1: Determine the impact of host immunity against key ectodomains or secreted components of the IMD, JAK/STAT, IsC1ql3, or ISARL pathways on the tick life cycle.
Aim 2: Determine the impact of host immunity against key components of the IMD, JAK/STAT, IsC1ql3 or ISARL pathways on pathogen acquisition and transmission.