Uncovering how tuberculosis transmits, $15.5 million, five-year grant from National Institutes of Health

Researchers: Kyu Rhee, associate professor of medicine and of microbiology and immunology at Weill Cornell Medicine (lead PI); Andrew Clark, professor of population genetics in the College of Arts and Sciences; Carl Nathan, chair of the Department of Microbiology and Immunology at Weill Cornell Medicine; Daniel Fitzgerald, director of the Center for Global Health at Weill Cornell Medicine; and Martin Wells, professor of statistical sciences in the School of Industrial and Labor Relations.     

This team will investigate the biology of how the tuberculosis bacteria survives and transmits infection through the air.

Prior to the arrival of COVID-19, tuberculosis (Tb) ranked as the leading cause of death from an infectious disease. Unlike COVID, Tb only transmits naturally to humans from other humans, and its transmission has not been studied in other hosts. It can remain silent in people for years before causing disease, limiting the effectiveness of existing methods to track and treat disease. Also, acquiring the disease doesn’t protect against reinfection. By learning more about the biology of transmission, the team hopes to identify candidate molecules for developing vaccines or drug targets that could reduce Tb’s infectiousness.

“For things where you’re forging new ground and creating new fields, that interaction is really critical.”

Kyu Rhee

The researchers will use an array of state-of-the art technologies to identify and study specific factors that enable Tb to successfully launch, fly and land from one host to the next. In Ithaca, Clark and Wells will analyze genome sequences of Tb variants from samples from Haiti and Moldova. As with COVID, the researchers plan to create a branching diagram, called a phylogenetic tree, that reveals the bacteria’s evolution and relationships between strains, showing how a descendant’s success is based on its increased transmissibility.

“A change in transmission is going to be informative about the biology,” Clark said. “It’ll tell us what mutations matter.”

Rhee said the academic integration office’s biannual symposia provided him with a survey of current thinking in related fields and exposed him to new opportunities for innovation and collaboration.

“The Academic Integration initiative is really quite special, if not powerful,” for bringing together the fundamental sciences at Ithaca and the clinical sciences at the medical college, Rhee said. “For things where you’re forging new ground and creating new fields, that interaction is really critical.”