I talked to Katie Henzler-Wildman, a professor of biochemistry and co-director of the NMR facility at UW–Madison, about her experience with the Biological Interactions Summer Research Program organized by WISCIENCE. During this ten-week program, visiting undergraduate students are placed in labs for intensive, hands-on research experience. Katie hosted Danielle Amaegbo from Austin College in her lab, helping her complete a research project.
To start, could you tell me a little about yourself?
I am a professor of biochemistry, and I’m co-director of the NMR facility. In my lab, the primary question driving us is understanding the molecular mechanism of how transporters and channels work. How do they move molecules across the membrane? In the case of channels, we want to understand how they recognize a signal and then open and close in response to allow some ions to flow. In the case of transporters, we want to understand how they function. In particular, we are interested in proton-coupled transporters. Cells have a proton-motive force across their membranes, basically a proton gradient and an electrical potential. And so we want to understand how they couple the movement of protons into bacteria to drive export of drugs out.
The particular examples we study are multi-drug efflux pumps that contribute to antibiotic resistance. And how do they use this sort of proton potential? You can think of it sort of akin to a water wheel, although it’s not a spinning mechanism for our pumps. But protons are allowed in in a controlled fashion, the same way water is allowed downhill with a water wheel in a controlled fashion. And then that energy is used to do some other work—in this case, pump antibiotics out of the cell.
So that’s what we want to understand. And we use a whole bunch of assays in bacteria to look at, you know, when we do different things with the transporter, we look at different substrates, can it still confer resistance? Does it actually reverse the effect of function to cause it to confer susceptibility? Weird things like this. And then we also use biochemical and biophysical tools to try to figure out on a very molecular level how these machines work.
We do a lot of NMR because it gives you information on proton binding, which is very hard to observe directly by other methods, and because it gives you information on both structure and dynamics. And so if you’re studying a pump like a little tiny machine, you want to know both what the structure is, what does it look like, and how does it move between different conformations to pump things out.
This is the first year your lab has worked with the BI program. What got you interested in working with them?
I started my lab at Wash U actually, and my lab there participated in some summer programs, particularly for high school students from diverse backgrounds. But then, when I moved to Wisconsin, there was a lot of just setting up the lab and taking over the facility. And so this was the year we got our act together to actually do this.
I have a number of grad students that are really invested in teaching and mentoring and are really dedicated to bringing undergrads into the lab. Because they’re the ones who do the day-to-day mentoring in the lab. So having grad students who are considering teaching as a career or otherwise really interested in developing their mentoring skills—I think that’s really important before you say okay, my lab is going to do this. Because I talk to students about their data, how to interpret it and how to talk about it, but I don’t do the day-to-day things, like here’s where the pipettes are, and here’s how we do this particular experiment step-by-step. So having grad students who are invested in that is important. So that’s sort of how we came to this point.
So what has it been like for you? How much interaction do you have with Danielle?
I have had less than I would have liked this summer because I was actually traveling for the first three weeks to give a talk and teach a workshop. But I’ve talked to Danielle about her data. So we look at the data and we talk about what it means, and what sort of controls are important. We’ve also talked about how to write her report.
And actually we had a funny conversation where she said, “But you gave such detailed feedback, usually you just get ‘This is wrong.’” But that doesn’t tell you what is right, and it’s really hard if you’re guessing in the dark. So I actually find I do a lot of mentoring on scientific communication skills. Because I think that’s the hard part. Undergraduate students can come in, they’re excited to learn, they learn how to follow a step-by-step protocol, they’re like, great, I’ve got this. But then how do you talk about that in a meaningful way? What are the important details to report and to share? And what are the details that go in your lab notebook but aren’t the thing you should lead with when you’re talking about it? So we’ve done more discussion of that. Like, what’s important to communicate? When you take that step back, what are the most important details about how you set up this experiment? Yes, like all these things are important, but what are the key features that someone needs to know to be able to understand what you did, what it means, and why it’s important.
Has there been anything that’s been surprising or unexpected for you working with the program?
No, not surprising. I just always forget how fast these summer programs go. They appear and then, yeah, you’re having conversations about their data, you’re having conversations about their career goals, different opportunities, and what does it really mean to work in industry versus the lab…and then, all of a sudden, you’re like, wait, they’re done in two weeks. So yeah, I think it’s just the speed that always catches me by surprise.
Yeah, 10 weeks. It sounds like a long time at first, but yeah, I’m sure it’s over in the blink of an eye.
Yes. She’s been getting great data. We’ve paired her up with one of my other undergrads who actually just started a couple months ago, so was also fairly new in the lab, but at least knows where things are. So they’ve been working together on a variety of projects, because then we can give the pair of them a bunch of different things to try, so they can each try a different transporter. And recognizing that this is real science and some are going to fail, and so it sort of gives a better guarantee that something will work. So they’re doing parallel experiments in some cases on different transporters or doing different aspects of the same experiment. It lets you go a little faster and really try a bunch of different techniques in the 10-week period. So they’ve done drug resistance screening in bacteria, they’ve done some cloning, and they actually purified protein successfully last week. A protein we’ve never purified before. So that’s really cool. And they’re gonna get to do a little NMR today. Yeah, it’s a little more range. Microbiology to biophysics.
And what’s the most rewarding part of it for you, working with this program?
I really love seeing the students in this program (and my other undergrads and even my grad students) figure out what they really want to do. Because I think a lot of students love science but they don’t really have a good handle on what careers you can actually do in science. What are the different options? Actually, last week I had a conversation with Danielle. She’s like, I had no idea that this was even a job people had. So it’s having conversations about what you love about what you’re doing, what you’re maybe not enamored with, what the different career options are, is grad school a good fit, and is this really what you want to do. And then sort of seeing their passion for science and helping them figure out exactly where they want to end up. As opposed to just saying, I want to do science and I want to go to grad school, because that’s what people do. Or, I want to do science, so I think I want to do med school. Helping undergrads figure out what the options are, and what it’s really like to work as a scientist, and see them discover that—I think that’s the most fun.
Yeah, that’s great. Like helping people find their path.
Yeah, yeah. And just help them get excited. And recognize what’s a big discovery when they stumble across it. A lot of times they’re like, this was a total failure and you’re like, no actually this is really useful information.
Do you have any advice or recommendations for other labs or faculty and staff who might be considering getting involved with the program?
I think thinking very carefully about what can be accomplished in 10 weeks is important. Having a reasonable project with some safe parts where you know the student is going to have some success, along with some riskier parts, because this is real science and this is what we want to try, and it may or may not work. And then also having a grad student or postdoc mentor who’s really invested and passionate about it. Because I think that makes a huge difference for the day-to-day experience of the students.