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Closeup of glossy nightshade
Image Credits: David Eickhoff (CC BY 2.0)

Unraveling the Molecular Evolution of Nightshade Plants: A Lab Spotlight with Dr. Yann-Ru Lou

Note: This interview has been edited slightly for clarity and cohesion but care was taken to preserve the interviewee’s original statements.

Dr. Yann-Ru Lou is an Assistant Professor in the Department of Plant Biology. Her lab focuses on implementing synthetic biology and biochemistry approaches to investigate the evolutionary trajectories of plant chemical diversity. I joined Dr. Lou’s lab in the Spring Quarter of my first year and enjoyed every moment of learning about research practices and working with nightshade plant metabolites. Nightshade plants belong to the Solanaceae family, including tomatoes, potatoes, and eggplants. The Solanaceae family produces acyl sugars, which are specialized metabolites for plant herbivory defense against insects and other pests. I would like to thank Dr. Lou for sharing her thoughts on science communication and giving us an opportunity to learn more about her research. Hope everyone enjoys this lab spotlight!

Research and project

Could you briefly describe the research projects that your lab currently does? What are the main goals of these projects?
Figure 1
Figure 1: Solanaceae Phylogeny Tree Showcasing the Evolution of Corresponding Modern Crops

My lab studies the evolution of specialized metabolites in plants, specifically the Solanaceae family. We’re mostly wondering how and why plants make structurally different compounds. Our underlying hypothesis is that the structural diversification of these compounds bears the fingerprints of the arms race between plants and insects, whose evolution often occurs dependently.

To study the plants’ evolution, we mainly focus on the molecular level by studying how pathways evolved and where enzymes come from. All plants share a common ancestor, and this common ancestor does not have all the beautiful pathways that lead to secondary metabolites of varying molecular structures. Therefore, the enzyme involved in the more evolutionarily-recent secondary metabolite must have evolved from somewhere. We study the molecular aspect of how acyltransferase (an enzyme used to catalyze acyl sugar biosynthesis) evolved and identify the number and identity of amino acids that are needed to switch or potentiate a new activity by the enzyme.

Then the other question is, considering how plants make so many different types of specialized metabolites, how can we test the evolutionary relationship between similar metabolites? It's hard to test these evolutionary hypotheses with natural plants because they differ not only in the analog [a structure in different organisms with similar functions but that has evolved independently] of specialized metabolites they make but also in their growth and phenotype, hence adding more noise in the background composition. If we think about coffee, there's still a good amount of coffee metabolite analogs or conjugated forms found in plants that we don't exactly know the function of. Another aspect that my lab is doing is using biochemical knowledge we learn from the molecular evolution study to do synthetic biology and bring in those pathways to an isogenic background [a gene might be modified in a model organism and then compared to other organisms that are genetically identical except for the modification]. We are testing the efficacy and activities of these compounds in a background that is comparable across the border of plant groups, and for us, it's within the Solanaceae family.

Are there any recent innovations or breakthroughs from your lab that you find particularly exciting? How would these advancements shape your other ongoing projects?

My lab mostly focuses on acyl sugars, which is a group of specialized metabolites in Solanaceae, a family including tomatoes and nightshades. We recently observed that the early division species in Solanaceae, or basal specieshad a shift of enzymatic activity compared to its ancestor. We think that we identified the time point when this shift exactly happened. It also seems like there's only a limited amount of amino acid changes, suggesting that it's a rather easy change in the evolutionary timeline for this to happen. So, the next question we have from here is: “Can we learn from this and design an enzyme for something that we want to do in medicine or industry?” I'm pretty excited about that.

What are the beauties and difficulties of working with plants in systems and synthetic biology?

I think the most challenging part is that there is a lot of noise that exists and acts as disturbances to experiments. We can always come up with hypotheses and models, but there is typically a need to replicate our experiments and extraneous variables to consider. In the experimental design process, we need to consider how to execute experiments while minimizing the noise. This is why many of the synthetic biology models and system designs are extremely complicated. For example, we can do experiments in controlled environments, like in greenhouses or growth chambers, but the experimental results under these replication conditions don’t hold 100% true when we put them out in the field.

And here comes the beauty of synthetic biology. We have methods to engineer plants with the knowledge from greenhouse experiments. We can then test these plants’ growth outside in fields and acquire a more thorough understanding of how these genetic changes affect the phenotypic performances of plants.  

What factors did you consider when you decided to research nightshade plants specifically?

There are many economically important crop plants from the nightshade plant family. Tomatoes and potatoes are the two of the most produced vegetable crops in the USA. There are also eggplants and petunias. Studying plants from the nightshade family comes with a lot of resources and collaboration opportunities that make researching these plants appealing.

A fun fact is that even thousands of years ago, humans had already started using Solanaceae and their specialized metabolites for medical purposes. Cleopatra, the Egyptian Queen from 51BCE to 30BCE, used Solanaceae alkaloids as eyedrops to dilute her pupils and make her eyes look bigger. That illustrates how long humans have been interacting with specialized metabolites in the Solanaceae family.

In your opinion, what is the importance of evolutionary research on the progression of translational applications?

I like evolutionary research because it provides information that can be applied to other levels of research, especially in the case of specialized metabolites. Many of them play a role in how plants interact with their environment. The more we understand about them, the more we can apply that knowledge in other applications. Plants have already survived nature for so long; there must be a strategy that works well for them. Although we don’t know how they designed the strategy, we can learn from what has been preserved throughout the millions of years of evolution to see whether we can use similar strategies to prepare our croplands in the future. Evolutionary research and translational applications are interwoven, and their significance to society is inseparable.

One particular example I can give is, as we notice throughout Solanaceae evolution, there is a specific type of acyl sugar—acyl glucose, built on a six-carbon glucose core—which has independently evolved more than two times. This triggers some questions: “Are these compounds more potent toward insects? Or are they just ‘cheaper’ to make in terms of plant energy expense?” To test for this, we use synthetic biology to generate plants that only produce acyl glucose and not other acyl sucroses. Then we can see insects behaving differently in response to those plants. We then ask the California tomato community if they notice similar behavior in the field under more complicated conditions and under abiotic and biotic stress at the same time. This could be a way that our crop plants can move forward to breed for endogenous defenses.

Science communication

How do you integrate your research activities into your teaching experiences, and what is your teaching philosophy as an educator?

I'm going to teach a systems and synthetic biology class in the spring quarter, which is a capstone class for synthetic biology majors. I designed the course to weave together all the knowledge that students have learned from their prerequisites and apply it to something going on in the synthetic biology field. Synthetic biology is a big field and there is a vast opportunity for research. One example is producing alternative meat using proteins or flavors from plants. I'm trying to build the framework so students will learn what real-life industrial pipelines look like. I’m hoping that students will be able to apply the information and knowledge that they have gained in their future jobs or research projects.

I’m curious about how you incorporate undergraduate students into your research lab. As a professor, what do you see are the values of involving us in cutting-edge biology research?

Honestly, we love it a lot. From personal experience, most undergrad students who join labs are enthusiastic about research, and contagious enthusiasm is beneficial to the lab atmosphere from a management perspective. On the other hand, I would say that UC Davis is trying very hard to push for course-based experiences, but in many cases, the traditional lab courses are kind of sugar-coating. So, I also like that when a prospective student joins us in the lab, they get an idea of how real-world research works. They often run into various challenges, which I think are good to run into when you are a student because you're not held accountable for that. They’re also learning the techniques in a more thorough, hands-on way. Overall, I encourage students to find a lab that they'd like to work in during undergrad.

Did you always know that you wanted to do research in biology and work in academia? What advice would you give to undergrads who are looking to pursue research in life sciences and plant biology?

I always felt I wanted to do research. When I was younger, I thought that I wanted to be a chemist. After I graduated college, I realized that the reason I wanted to do research was that I basically didn't know what other professions involved. I tried 10 different part-time jobs, but then I realized that I really like doing research and the mindset of researchers. It's curiosity-based and you have a lot of soul-crushing moments, but there is never a dull moment. Then I went to grad school where I studied plant-specialized metabolites. The next question became, “How do plants make these compounds?” This became a biochemical question. And after studying the pathways and enzymes of the plants, the question became: “How do plants evolve?” And suddenly, this became an evolutionary question. Overall, my journey is very curiosity-driven.

Anything else you would like to add?

For undergraduates, I think practicing is the biggest thing. Practice a good attitude while learning. Research is hard and everyone makes mistakes, so don't hold yourself accountable and improve upon those mistakes. Then the other thing is that research is really hard because many times you're pushing the limit on something that we don’t have an answer to because there isn’t available human knowledge to certain questions. This is a mindset that we should encourage people to adopt so they understand that even negative results are good results. With any result, always try to improve on the technique. Overall for undergrads, the experiences are most valuable. If you're really putting in the thought, the time, and the effort, you will contribute to research.

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