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Patel Lab earns new grant to study evolutionary trade-offs between reproduction and aging

Posted by on Monday, February 14, 2022 in Uncategorized.

By: Andy Flick, Evolutionary Studies Initiative scientific coordinator 

Assistant Professor of Biological Sciences Maulik Patel and his lab have received a Pilot Research Grant from the Vanderbilt Evolutionary Studies Initiative to study reproduction and aging.

Submitted Photo | Patel, Held and their team take a basic science approach to study mitochondrial homeostasis.

According to one theory in evolution, aging is the price animals pay for reproduction. Research in the Patel lab uses the tiny but experimentally mighty roundworm model organisms Caenorhabditis elegans to examine the connection. The researchers employ CRISPR genome engineering technology to determine what genes affect which cellular processes or correct cellular glitches. 

“The challenge has always been to identify the molecular basis for the evolutionary tradeoff between (somatic) body maintenance and reproduction,” Patel said. “Using C. elegans and a fluorescent reporter provides an elegant framework to think about this tradeoff and, more generally, how we age.” 

Ph.D. candidate James Held, who is participating in the work, said, “We decided to study the soma-reproductive tradeoff because the associated phenotype that we serendipitously came across was just too remarkable not to follow up on.” 

The researchers use a fluorescent reporter that illuminates cells when their mitochondria, or power center, stop working. The reporter signals that the cell has employed a process to help the impaired mitochondria, the mitochondrial unfolded protein response, or UPRmt for short. 

“The fluorescent reporter … gives us a quantifiable way to measure distress,” Patel said. “Historically, studies use lifespan as a measure of maintenance. However, lifespan is a complex phenotype, measurements are notoriously variable and the biological significance of small differences is not always clear.” By using mitochondrial distress, the lab has a quantifiable and practical way to measure changes in somatic maintenance. 

Held described the process he used that led to questions about the tradeoff: “I created a mutant in which a protein called HOE-1 cannot leave the nucleus because its nuclear export signal—NES for short—is compromised. I found that the NES mutant robustly induces UPRmt, seen most obviously by activation of the UPRmt reporter.” These mutants grew normally but were sterile and could not reproduce. 

They then wanted to clarify the role the HOE-1 protein played in activating UPRmt. “Thus, to complement the NES mutant, I made a strain in which nuclear HOE-1 is overexpressed. Surprisingly, UPRmt is not activated in these animals.” 

Held noticed that the main difference between the NES mutant and complementary mutant was that the complementary one was not sterile—which led to the link in a tradeoff between maintenance and reproduction. 

According to Patel, “Given the importance of the topic and the exciting findings, this new project will be a major focus of the lab. I’m really excited to see where James and the other trainees can help take this project.” 

The ESI grant may fundamentally expand the work conducted in Patel’s lab and will provide preliminary data to seed a larger National Institutes of Health (NIH) grant this summer.