CROSS-KINGDOM IMMUNE PATHWAYS IN TICKS
This NIH-supported grant is an interdisciplinary, collaborative effort among four institutions across the United States, under the leadership of the Pal lab. Our group specifically investigates cross-kingdom signaling pathways that are relevant to the transmission and persistence of Lyme disease. See here for our discovery of a new twist in host-pathogen interactions.
DECIPHERING THE TICK GENOME
The tick is an ancient and unique arthropod that, despite years of research, remains enigmatic. The genome of the whole tick could help to uncover more information about Ixodes scapularis biology. Our lab, supported by outside collaborators, recently sequenced and assembled the Ixodes tick genome, which was subsequently annotated by NCBI (see below) and VectorBase (see here). This improved I. scapularis genome is expected to serve as a key resource for fostering the much-needed research on tick biology and prevention of tick-borne infections.
STRUCTURE, FUNCTION, AND VIRULENCE ATTRIBUTES OF BORRELIA PROTEINS
This is one of our long-term NIH-supported studies (project start date: 01-July-2009; current end date 31-July-2025), which focuses on understanding how a select set of proteins from the Lyme disease pathogen can support microbial survival and virulence in vivo. We are specifically addressing how these unique proteins of undefined functions contribute to pathogen persistence in the tick-rodent infection cycle and pathogenesis in mammalian hosts. Knowledge of these processes is critical for the development of novel preventive and/or therapeutic strategies to combat the infection.
NOVEL THERAPEUTICS FOR LYME DISEASE
As part of our ongoing efforts and collaborations with our partners at NCATS, we are pursuing the development of new and improved antimicrobials against Lyme disease pathogens, via the targeting of unique and essential protein-protein interactions that the pathogen employs for infectivity and persistence in mammalian hosts. This involves the use of cutting-edge quantitative high-throughput drug discovery platforms.
DEVELOPMENT OF TICK IMMUNITY IN MAMMALIAN HOSTS
In our ongoing attempts to develop a Lyme disease vaccine, we are pursuing the concept of "acquired tick immunity". Some rodents, such as guinea pigs, have displayed signs of tick resistance after multiple encounters. In such cases, ticks have been noted to feed less and drop off sooner. We hope to better understand the mechanisms behind this acquired tick immunity, as it could help to pinpoint vaccine targets. Currently, with the support of extramurally-funded grants and contracts, we are attempting to evaluate the efficacy of select tick antigens (associated either with the genesis of acquired tick immunity, or the support of various aspects of tick physiology, such as blood meal acquisition) as anti-tick vaccinogens.
NOVEL VACCINE USING THE RABIES VIRUS PLATFORM
Under the support of NIH, we will explore the potential of tick and bacterial proteins to protect against Lyme disease. With our partners at TJU, we will incorporate essential target proteins into the widely-used rabies virus system, in an effort to develop safe and effective preventive strategies.
TICK-BORNE DISEASES IN A HUMAN MODEL
We are taking a groundbreaking interdisciplinary approach to Lyme disease with this DoD-funded project. In a collaboration with USUHS and Johns Hopkins University, we will use 3D models of human blood vessels to study the dissemination of the pathogen throughout the human body.