ISSUE 1
How do pathogens replicate at the molecular level?
Spotlight on Elizabeth Campbell, the Corinne P. Greenberg Women & Science Professor and head of the Laboratory of Molecular Pathogenesis
The landscape of human pathogens is vast. Rockefeller professor Elizabeth Campbell works with two of the deadliest: the bacteria that causes tuberculosis—one of the most ancient diseases—and the virus that causes covid, a relatively new disease.
Researchers want to understand what makes pathogens good at entering and infecting the human body and how they replicate once they are there. They also want to understand—in mechanistic detail—how an antibiotic kills a pathogen.
Humanity’s struggle with pathogens is often likened to the one-upmanship of the Spy Vs. Spy comic in Mad magazine. Humans innovate—antibiotics and antivirals. Pathogens mutate. This microbial arms race is causing a crisis in antibiotic resilience.
The Challenge
Liz Campbell is arriving at innovative solutions by focusing on one of the most basic processes in biology—what biologists call “the central dogma” and high school students learn in their first biology class: how genetic information flows from DNA to RNA to proteins. The first step in that process is called transcription where an RNA copy is made of a gene’s DNA sequence.
Transcription is complicated and varies from pathogen to pathogen, but it is also essential for life, making it a fantastic target to inhibit pathogen proliferation.
Dr. Campbell’s Approach
The transcription factor that upregulates antibiotic resistance in the bacterium that causes tuberculosis.
Using cryo-electron microscopy, Liz Campbell is visualizing—at the scale of individual atoms—the sequence of events in transcription and finding new ways to disrupt the process. Dr. Campbell and her team discovered a swivel action in the enzyme central to transcription, and in collaboration with Rockefeller’s Jeremy Rock, showed how it plays a role in antibiotic resistance in tuberculosis. They are currently exploring ways to gum up the movement in much the same way that grains of sand can stop a gear from turning.
Tuberculosis is the leading cause of death in the antibiotic era. Because tuberculosis is not a chronic illness that requires a lifetime of medications to treat (think statins and cholesterol), finding new antibiotics to treat drug-resistant tuberculosis infections is not a good investment for drug companies. Finding new drugs to treat infections relies heavily on academic research, such as Dr. Campbell’s.
How This Could Improve Our Lives
By uncovering novel paradigms and never-before-seen molecular details, Dr. Campbell and her team are rewriting the textbook descriptions of how our cells “read” our genes and laying the groundwork for innovative therapeutic strategies that could interrupt these these processes in pathogens. “While our current focus is on fundamental principles, our work exemplifies how basic science can drive translational research forward,” says Dr. Campbell.
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