In Jake Brunkard’s lab in the Genetics-Biotechnology Center, you’ll find plants everywhere. The space is filled with grow carts containing tomatoes and Arabidopsis thaliana, a member of the mustard family that Brunkard calls “the lab rat” of the plant genetics world. You’ll also see Nicotiana benthamiana, a tough survivor of the Australian Outback, where it flourishes in rocky soil, high heat, and low-nutrient conditions. The flora (and the science) extend beyond laboratory walls to the university’s agricultural research stations, which host maize and soybeans in summer fields, and to UW greenhouses during the cold months.

Brunkard, associate professor of genetics, and his lab concentrate on the TOR cell signaling pathway, by which plants, on a molecular level, sense the availability of nutrients that prompt growth. Eventually, what they learn may help food crops get by with less added nutrients in the form of fertilizer— by lending them some “Outback toughness” genes — thereby making agriculture more sustainable.

What is TOR, and what does it do in plants, animals, and other life forms?
A group of scientists went to Rapa Nui, also known as Easter Island, back in the 1960s. Inspired by the penicillin discovery story, they were looking for useful drugs from microbes. They screened soil from the island and discovered a chemical they called rapamycin. No one knew what it was for, and it turns out it is found in the soil all over the world; but, eventually, it was discovered that it regulates this cellular signaling pathway called TOR, which stands for target of rapamycin. The pathway controls growth, metabolism, and lifespan in all eukaryotic species. In humans, the mTOR (mammalian TOR) pathway is implicated in many cancers, causing cells to grow wildly. Rapamycin is used in cancer treatment and transplant medicine to quell organ rejection. In plants, it regulates growth in response to nutrients and other growth factors. It really does show how basic science can lead to a giant field that has such important implications for human and animal health, and for plant health as well.

Why are you interested in TOR?
First, I’m interested in the evolutionary perspective on this. TOR has been really well studied in mammalian systems and in models, but it’s not often studied with an evolutionary perspective on how this signaling pathway, which has existed for a very long time, has evolved or changed or been modulated. One possibility is that plants have evolved a totally new way of sensing nutrients and controlling growth through this TOR pathway, but that’s not very satisfying. It seems likely that there are many similarities in the TOR pathway between humans and plants. We’re interested in the conserved pathway that’s shared across 2 billion years of evolution. How do these things evolve?

What could a better understanding of TOR lead to for crop plants?
It’s well-accepted that our agricultural system is not sustainable. To get the crop yields that we get, we have to apply huge amounts of fertilizer to our soils, and fertilizers are finite resources. Phosphorus is a rock that we mine from the earth. In the coming decades, we’re going to deplete our phosphorus mines.

The other thing is we apply all this fertilizer, and the plants barely use it. We need to overload the system to get them to take up even a fraction of what we apply. The rest gets into our waterways, and you get those green algal blooms. So, if we could understand better how plants are sensing and responding to nutrients and how they’re using those nutrients to make the kernels of the corn (as opposed to the leaves), then there might be ways to tweak the process that would be really useful for agriculture. This could be a way to improve crops that would never be achieved using traditional breeding approaches.

We do a lot of work with an Australian plant, Nicotiana benthamiana, which we affectionately call benthi. It grows in rocky deserts. It’s just the most robust plant you’ve ever encountered — it can grow anywhere. And it’s a great tool for plant biology because we can grow it easily, anywhere we want to, and it’s really easy to transfect with viruses. It has figured out how to make do with less. So, if we can understand better how it does that, maybe we could give a little bit of that ability to some of our agricultural crops.

How would you go about doing that?
To do that, we can use the exact same human drug, rapamycin, because the proteins are the same. We can add rapamycin and other TOR inhibitors to plants and measure what happens in response to inhibiting TOR. We look at gene expression and ask several questions: What genes are being transcribed? Which of those genes are being translated into proteins? Of those proteins, which ones are stable or unstable? How are those proteins being modified? We’re trying to really map everything that TOR is doing to control the expression of the genome using those inhibitors.

How does interest in TOR drive studies in your laboratory?
The most honest answer for why I study TOR is that TOR connects to so much of biology in so many different ways. When I was starting my lab, I really wanted to have a simple organizing principle so that when a brilliant student comes along who wants to work on something, we can find a way to make it work with TOR. If a student wants to study some sort of plant disease, we can study that. Or I have a student who wanted to sequence the genome of a plant, so we sequenced the genome of a plant in Australia that he was really excited about. Everything has a connection to TOR in some way. And it’s just been a great way to organize a lab around creativity and thinking about dynamic science while not being limited by a topic.

You’re working with Dudley Lamming, an associate professor in the UW School of Medicine and Public Health, on a project to create corn and soy protein that is better for human health. Is TOR involved there?
Yes, actually, it is. Dudley is a leader in the rapamycin and mTOR field, and that’s how we connected in the first place. Seeds like soybeans make huge amounts of protein from just a couple of genes; there are three to five genes that are making something like 80% of the protein in a seed. We have no idea how that’s regulated, but we think TOR is involved for various reasons. So, the secret side project is that I’m trying to understand the regulatory process and whether we could tweak it in some way that could let us modulate the nutritional properties of seeds even further. The goal is to create soy and corn products with lower levels of the essential amino acids isoleucine and histidine to promote weight loss and better glucose tolerance.

Some of these interventions for human health might be tricky to actually implement, and it might be easier to do some of these things with pets, where we can control their diet a little bit more easily. Wouldn’t it be cool if some of this not only helps human health but also helps our pets have healthier lives? We’re changing the proteins in soybean to make them healthier calories. A lot of what pets eat is soybean and corn that’s been ground up into meal. If we can have them eating a healthier version, that’d be incredible. That’s a main motivation for that whole project: I’ve got a 2-year-old puppy, and wouldn’t it be cool if I can get him on a healthier diet in just a few years?

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Federally Supported Research

Jake Brunkard’s lab has received federal funding from the National Institutes of Health, the National Science Foundation, and the U.S. Department of Agriculture. His research also has been supported by the nonprofit Howard Hughes Medical Institute and the Wisconsin Partnership Program.

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This article was posted in Basic Science, Health and Wellness, Healthy Ecosystems, Living Science, Summer 2025 and tagged Animal health, cell signaling, fertilizer, Genetics, Genetics-Biotechnology Center, Jake Brunkard, mTOR, sustainability, target of rapamycin.