$4.3M NIH Grant Awarded to Study, Co-led by Alissa Rothchild, Aimed at Battling Tuberculosis-infected Cells
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Tuberculosis, caused by the bacterium Mycobacterium tuberculosis (Mtb), kills upwards of 1.2 million people a year, making it one of the leading causes of death by an infectious agent worldwide. How, exactly, Mtb evades the immune system isn’t yet known, but over the last decade UMass Amherst has assembled one of New England’s premiere teams to help figure out how.
And now, thanks to a $4.3 million grant from the National Institutes of Health, which Alissa Rothchild, assistant professor in the College of Natural Sciences's Department of Veterinary and Animal Sciences (VASCI), is co-leading, UMass Amherst’s researchers are going to be investigating the mysteries of programmed cell death.
Mtb researchers have recently taken a great interest in programmed cell death as a potential means for either control or dissemination of bacteria. Nothing lives forever, and our bodies have a number of different mechanisms for killing off their own cells in order to keep us healthy.
Once a person breathes in an Mtb bacterium, it infects specific lung cells, called alveolar macrophages, which, ironically, are the first line of defense in fighting infections. Once inside an alveolar macrophage, Mtb can replicate efficiently and eventually spread into neighboring cells.
“Mtb effectively turns the alveolar macrophage into a Trojan horse, where the bacteria can hide from the body’s defenses,” says Rothchild. “But what would happen if the infected macrophage was killed off early on during infection before Mtb had a chance to replicate? We want to understand whether programmed cell death of infected macrophages leads to different outcomes depending on when and where it happens.”
That’s exactly what Rothchild and her graduate student, Bismark Minnah, along with their collaborators at Seattle Children’s Hospital, Shuyi Ma and Alexis Kaushansky, are going to spend the next five years researching.
Their hunch is that ferroptosis, a specific kind of programmed cell death mediated by iron, could be the key—if the cellular mechanisms that protect against ferroptosis in macrophages can be turned off.
“Alveolar macrophages are programmed to resist ferroptosis,” says Rothchild, “but maybe, in the case of tuberculosis, killing those infected cells off early could be a new way forward in the fight for public health.”
This story was originally published by the UMass News Office.