PROJECT 2
Project 2 is focused on the interplay between tick metabolism and immune pathways, and how these influence the vectorial competence and developmental processes of Ixodes scapularis. Through evolution, ticks gained unique physiological adaptations, including tightly-regulated metabolic processes, that allow prolonged blood feeding on hosts and tolerance to microbes that are pathogenic to humans. Our previous studies identified several tick pathways that are activated by host- or infection-derived molecules that integrate arthropod immunity and metabolism, and showed that vectorial competence in ticks is influenced by immune and hormonal signaling, intersecting with tick development and metabolism. For example, the Project 2 studies, led by Dr. Joao Pedra of the University of Maryland School of Medicine, characterized a non-canonical immune deficiency (IMD) pathway that responds to infection-derived lipids, in a network that is initiated by an I. scapularis surface protein called Croquemort, which altogether regulates tick immune responses and metamorphosis.
For the current cycle of this P01, Project 2 will continue to investigate the nexus between immunity, metabolism, and development in ticks. The team will explore how Ixodes immune responses are intertwined with tick metabolism, particularly how they influence the physiology and vectorial competence of I. scapularis. Ongoing studies will assess how tick signaling pathways regulate metabolism at the cellular and organismal levels and during infection, and in turn, how the metabolism of I. scapularis affects immune signaling, biological fitness, and pathogen transit. Altogether, this project will address the emerging concept that immunity and metabolism operate within a physiological framework in ticks.
Specific Aims
Metabolic pathways regulating tick immune responses
Aim 1: To assess how the JAK/STAT, IMD and ISARL pathways influence I. scapularis metabolism during blood-feeding and infection
Aim 2: To determine the contribution of I. scapularis metabolism to immune signaling upon microbial acquisition
and transmission