Scientist Profile – Professor Zeba Wunderlich
Zeba Wunderlich, Ph.D.
Associate Professor of Biology
By studying gene regulation in the embryonic development and immune response of Drosophila, the Wunderlich Lab investigates how a gene regulatory network’s tasks influence that network’s architecture, robustness, and evolvability.
The lab’s principal investigator, Professor Zeba Wunderlich, reflected on what fascinates her about gene regulation and what she loves most about being a scientist, then talked a bit about gardening, books, and pasta.
How would you describe your research and the goals of your lab?
We have an identical copy of DNA in every one of our cells, but of course our cells can have extremely different jobs, and the reason they can perform those different jobs is that they express different genes. For instance, a muscle cell will turn on a whole bunch of muscle-specific genes that allow it to do its job of forming a fiber and contracting, and a neuron will turn on a distinctive set of genes that allow it to relay signals. The primary question my lab asks is how are those instructions—the ones turning genes on in certain cells or under certain conditions—how are they written into the genome? And we explore that question using fruit flies as a model. We examine how genes are turned on and off in the flies’ early development as well as in the context of flies’ defense against bacterial infections.
Why do you focus on these two particular models of gene regulation?
One thing that’s interesting about gene regulation in development versus immune response is that embryonic development is not so variable from one individual to the next. Fly embryos go through the same processes at about the same time points and their adult body proportions are similar from one to the next, even if they’re genetically distinct and regardless of other environmental variation. Gene regulation as part of immune response is very different. If you give a whole bunch of fruit flies the same pathogen, they don’t always turn on the same genes to the same levels, and some animals will live and some animals will die. In one study, we gave genetically distinct animals the same infections and measured what genes turned on, and how strongly, and how that was encoded in the genome. We also have an ongoing study that involves locating the specific genomic regions that have instructions for turning on the immune response. We can systematically screen the whole genome by transfecting cells and seeing which pieces of DNA will turn on a gene in response to an immune stimulus.
Can you share any recent findings from your lab that you’re really excited about?
I can tell you about an interesting new technique we developed recently. For a long time, when we were studying gene regulation with respect to flies’ immune response, we had to make frustrating choices about what we wanted to measure. For instance, you can choose to measure survival time by giving the animal an infection and observing how long it takes to die. Alternately you can infect the animal and measure the amount of bacteria after a certain amount of time, but you have to sacrifice the animal to do it—you grind it up, plate and examine the solution, and count how many bacterial colonies came out of it. We wanted to be able to measure both bacterial growth and survival time in the same animal instead of having to choose. So, we partnered with an expert in bioluminescence to make bacteria that glow with the hope that we could then observe that bacteria in the flies without having to kill them. There were reasons that we weren’t sure this would work. For instance, flies are not as clear as, say, a zebrafish embryo, so we weren’t sure that we would get enough signal. But it turns out it does work, which is awesome!
What drew you to this area of research?
One of the reasons that I like working on gene regulation is because it looks like it should be a mess. Many levels of organization are necessary for gene expression to happen correctly. For example, our DNA needs to get folded into our cells, and some parts are tightly folded and some—usually the parts where the genes are being expressed—are relatively open. And that’s a complicated problem because our genomes are huge. Also, when you turn on a gene, you have all these relatively weak molecular interactions that need to occur inside a nucleus that’s densely packed with proteins and DNA. That’s what I mean by it seems like it should be a mess. It’s fascinating that it all somehow manages to work because we would probably never design a system that functions this way.
What would you say is your favorite part of being a scientist?
I think it’s two things. On the scientific end, many scientists like a puzzle, right? We’ve come up with these questions that we want to address, and that point when you get multiple pieces of evidence that start coming together and give you that picture of what’s really going on, I think that’s incredibly satisfying. The other aspect I love is training people in the lab. I’ve worked with trainees ranging from high school students to postdocs and I love seeing them grow as scientists and as people. They attempt very difficult things, and they make them work. It’s great supporting them through that process and witnessing their victories.
What are your favorite activities or hobbies outside of the lab?
I like houseplants, and I like gardening. I like looking at plants in different places. I would garden for food, but my backyard is extremely shady, so I go mainly for aesthetics.
Favorite book?
Off the top of my head, for relaxation I like Ellen Hildebrand’s novels. They’re not very literary but they are fun, and they all take place on Nantucket, which I’ve never visited but I still like reading about. Another that comes to mind is A Wrinkle in Time. I’ve always loved that book and I’ve read it a million times.
Favorite food?
Pasta! I’ve only been to Italy once. It was glorious. Now I go to Eataly until I can get back to Italy.
*This interview was conducted and edited by Jim Cooney.