Host Tropism of Lyme Disease Bacteria
We aim to define the mechanisms that drive host-specific Lyme disease infection so that strategies targeting these mechanisms can be developed to block transmission to humans.
We have developed artificial tick feeding chambers as well as various models of infection in our laboratory. These laboratory infection models and inoculation methodologies allow us to investigate the host-specific complement evasion of polymorphic Lyme borreliae proteins that promote spirochete transmission and dissemination in mammals and birds.
Capillary feeding to infect ticks or collect tick saliva
In a longitudinal, 6-year study performed in collaboration with Drs. Maria Diuk-Wasser at Columbia University and Sergios Kolokotronis at SUNY Downstate, we are sequencing the polymorphic Lyme borreliae genes from ticks feeding on mammals and birds on Block Island, RI using deep amplicon, long-read sequencing. The results will allow us to identify alleles preferentially present in such ticks in nature, providing insight into the dominant alleles of the polymorphic Lyme borreliae genes in rodent and bird species circulating on an island ecosystem.
We are employing transposon sequencing technology (Tn-Seq) to identify transposon mutants of Lyme disease that display enhanced ability to survive in ticks feeding on mammalian and avian blood and/or confer increased colonization or increased fitness in the bloodstream of mammals and birds.
Lyme Disease Prevention
We aim to generate a safe and potent vaccine and prophylaxis to protect humans from Lyme disease infection.
In collaboration with Dr. Maria-Elena Bottazzi at Baylor College of Medicine, we are optimizing the production process for CspZ-YA vaccine and formulating this antigen with commonly used adjuvants. We will ascertain the minimal dose of the vaccine (evaluating various inoculating routes and adjuvants) that prevents Lyme borreliae colonization and manifestation. This information will allow us to define the ideal condition that enables CspZ-YA to display the most efficacious prevention against Lyme disease.
The structure of CspZ-FH binding complex. Source: PDB #6ATG; http://www.rcsb.org/structure/6ATG.
Our collaborators, Dr. Jon Lovell at SUNY Buffalo and Dr. Kaspars Tars at Lativia Research and Study Centre, have recently developed cobalt chelated porphyrin-phospholipid (CoPoP) and Q-β virus-like particles (VLP) as novel adjuvants. We are conjugating several Lyme borreliae vaccine antigen candidates and evaluating the ability of these adjuvants to provide better immunogenicity and efficacy in preventing Lyme Disease infection.
With Dr. Robert Linhardt at Rensselaer Polytechnic Institute, we are testing the synthesized analogous compounds of glycosaminoglycans (GAGs) as prophylaxis to prevent spirochete colonization and Lyme disease-associated manifestations.
Early Lyme Disease Diagnosis
We aim to develop a rapid, easy to use platform that combines the high sensitivity of ELISA/IFA with the specificity of the Western blot for the diagnosis of Lyme disease in the early stages.
Through our collaboration with Dr. Nate Cady of SUNY Polytechnic Institute and Ciencia, Inc, the Connecticut-based company, we are developing a high throughput, chip-based platform for early Lyme disease diagnosis using grating coupled surface plasmon resonance (GC-SPR) and fluorescence mode of GC-SPR (GC-FP).