Complexity is genomicist Meru Sadhu’s best friend

Prabarna Ganguly, Ph.D. April 07, 2022 PRESS CONTACT

Genomics was not Meru Sadhu’s first academic love.

“I wanted to be a paleontologist and study dinosaur bones. The only dream that made sense for a four-year-old!” says Sadhu.

But instead of working at an active dig site, Sadhu was exposed to the world of research at a young age. His parents worked at a pharmaceutical company, and they used to take Sadhu to their work site where he would watch them perform all kinds of biological research.

For Sadhu, the decision to pursue a degree in science was propelled by his desire to make discoveries. He took his first genetics class during his third year at Caltech, and he realized the remarkable novelty of the field. Instead of simply being taught facts, Sadhu felt like he was finally being asked to observe and discover the complexities of biology.

“That you can get such complex systems starting with the simple rules of genetic inheritance really appealed to me, and my fascination with it remains to this day,” says Sadhu.

Sadhu is an Earl Stadtman Investigator and head of the systems biology and genome engineering section within the Intramural Research Program of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health. In a conversation with science writer Prabarna Ganguly, Sadhu discusses his research and why yeast have a special place in his heart. He even provides a small gardening tip.

This interview has been edited and condensed for clarity.

Ganguly: You started your laboratory in the Intramural Research Program at NHGRI in 2018. What kind of truth about biology are you most interested in uncovering?

Sadhu: My goals are similar to what genetics researchers have tried to understand for over a century. What are the genetics’ underlying traits? What makes them so complex? My laboratory is committed to teasing apart some of that complexity. We use experimental techniques to look at thousands of different genomic variants to understand how each of those variants and the environment influence the particular traits.

Ganguly: Why is yeast one of your favorite organisms to use for studying genetics?

Sadhu: There are so many reasons. Yeast have a lot of genes that are conserved with other organisms, including humans. Yeast are also a wonderfully rigorous system to study because you can control their environment so tightly; every input can be controlled. Also, you can do experiments with millions or even billions of yeast cells, and you can understand what's happening in those millions or billions of cells individually, even if they are in one single pool.

Ganguly: Are you studying a particular trait or behavior in yeast?

Sadhu: Yeast do this interesting thing in the wild — they kill each other with toxins they secrete. These toxins are not lethal to the yeast that secrete them, so they are therefore protected; it's a way to kill neighboring yeasts that are not toxin secretors. We are trying to understand if there was any selective evolutionary pressure for those yeast to become resistant to these toxins.

Ganguly: And are there yeast with toxin resistance?

Sadhu: We set out to look for yeast protecting themselves against secreted toxins. We did this by looking across yeast populations and found that yeast do vary in terms of their resistance. We were also able to identify a single gene that seems to be a major contributor to toxin resistance.

Ganguly: Given that many of us are working from home, have you taken up any hobbies lately?

Sadhu: My partner and I got a house with a garden, so I've been learning how to garden. Lots of cherry tomatoes. Also, fun fact — we planted a tree called serviceberry that has quite tasty berries in May and June. It's a really common tree in this area, but I don’t think most people are aware of it!

Ganguly: Nothing like some good gardening advice. What are you looking forward to seeing happen in genomics over the coming years?

Sadhu: I’m genuinely excited about the work being done to understand human history through genetics and genomics: the record in our DNA, how it provides a map of who we have met and where we have been. But I also think it’s critical to do such research being aware and respectful of the societal and cultural context.

Last updated: April 7, 2022