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Catherine Drennan: Catalyzing new approaches in research and education to meet the climate challenge

Leda Zimmerman    ·    May 15, 2019    ·    MITEI

Listen to the bonus interview:

Katie Luu: From MIT, this is the Energy Initiative. I’m Katie Luu. Today we’re talking with Cathy Drennan, professor of biology and chemistry at MIT, and professor and investigator at the Howard Hughes Medical Institute.

Your research centers on microbes. Can you define what microbes are for audience members who may be brand new to this topic?

Catherine Drennan: The “micro” part of it is small. Small things, small microorganisms, bacteria. That’s what a microbe is, something that is tiny. We’re not talking about humans here. We might be talking about the bacteria that lives in your gut, though.

KL: They’re microorganisms that also help with fermentation processes?

CD: Oh, yeah, microorganisms are great. A lot of people, when they think about, it’s like, well, if you care about beer, for example, then you probably care about some of the processes that are going on with microbes.

KL: Is that how you came to microbes?

CD: Not so much. I became very interested in understanding the cool chemistry. When I say that, if I take a step back to high school, I was not a fan of chemistry in high school, I have to admit now. In my title, you heard professor of chemistry as part of my title. I did not find chemistry interesting. Then I went to college. I said, I’m really interested in understanding fundamentals of how a living organism works. How does it do what it does? How does it survive? Where does it get its energy from? What is going on? What is the essence of this? Someone said, that’s chemical reactions. It’s chemistry. I was like, oh no, I took a chemistry course, that can’t possibly be the case. I took chemistry, it was required. I was like, wow, this is fascinating. This is the fundamentals of life, these chemical reactions. Then I said, okay, what are the most challenging of these chemical reactions that happen in the body? What are the coolest ones?

I have to say, no disrespect to humans, but a lot of the coolest chemistry is actually happening in microbes. They make crazy stuff like vitamins. We need vitamins. There are crazy scaffolds of things that do chemistry in our body, but humans are like, let’s let a microbe make it and we’ll ingest it, thank you. The microbes are doing the hard chemistry there. It’s like CO2 in the environment and you want to fix that into another carbon thing like acetate. Microbes do that. A lot of really hard chemistry, splitting nitrogen, triple bond. There’s lots of nitrogen in the environment, but we need to break it down to actually use it to make proteins and do other things. Can we do it? No. Microbes? Yes. Microbes can do that. I just wanted to understand the coolest chemical reactions. When I went that direction, I found myself studying microbes.

KL: How does that relate to energy and your work with solving environmental problems?

CD: I’ve always cared about the environment. I was just an outdoors person. I realized that we needed to think about where our energy is coming from, how we’re doing reactions. That a lot of the time the way that we do things is not very good for our environment. Microbes can do a lot of that same chemistry but they do it in a much cleaner way. That brought me to it. In studying these challenging reactions, I often found myself studying things that were very important for energy or the environment. Because microbes are doing the hard stuff, like taking CO2 or CO out of our environment, fixing it into other carbon sources, splitting nitrogen, doing hydrogenous chemistry so we have hydrogen fuel cells. Microbes are doing those same reactions. I found myself studying how nature does it and saying, can we apply some of this knowledge to having cleaner ways to do things in industry?

KL: What are some applications of your research that you’ve seen in industry so far?

CD: Some people have been very interested in the carbon dioxide work. We study enzymes that bind carbon dioxide and fix it, remove it from the environment. They’re complicated, they have metals in them, and there are proteins with metals that do this chemistry. We’ve been studying kind of how they work. But there are companies now, LanzaTech is one of them, that are really trying to use the microbes that have these enzymes and do these reactions, to take carbon dioxide and make it into other things. Their dream is, put one plant, attach it to another plant, one plant is releasing carbon dioxide, have the other one take that carbon dioxide and make it into something like jet fuel. This is all very early days. There are, of course, a lot of skeptics about whether everything is going to work. Some of the first plants are open and we’ll see what happens. I feel like it always takes time to get new technology to work. I love the fact that people are being adventurous and creative and trying new things. We’ll see what works and doesn’t. But we’ve got to venture out of our comfort zone and try new things.

KL: I was reading about some of your other recent micro research. I saw an article that talked about how it can be used to clean up oil spills. Can you dive into that a little bit?

CD: Definitely in the category of cool chemistry that enzymes and microbes do. Microbes are amazing. They need carbon for life. Everything needs carbon for life. Very important. There are microbes that will take whatever carbon you give it and try to figure out a way of, how can I break this and turn it into something that I can use? How can I transform it into something that I need?

There’s a lot of products in oil spills, crude oil, hydrocarbons. There are hydrocarbons, there’s carbon, that’s great. But they are not reactive forms of that. They’re really inert compounds. That’s the problem with oil spills. It’s very inert. A lot of times the products sink down to the bottom or you’re way away from oxygen, even. Oxygen is a great thing to do chemistry, but you’re away from that. You’re in very inert environments. Toluene and other things that are in crude oil, they’ll just sit there for a really, really long time. But some microbes have found a way to actually use that, to break it down. What they do in the beginning is they have this metalloprotein that we’ve studied. They take this and go, okay, this group is hard to do anything with. But I’m going to stick another group onto it. I’m going to add this other molecule that has more handles on it and I’ll stick them together. Once I’ve done that, there are other enzymes in place that can now deal with it. They can bind it and break it down.

We study these microbes that basically live off this stuff that is components of crude oil. A lot of people are very interested in this idea of, can we either take the enzymes or the organisms and put them in areas where there are these oil spills and just let them clean it up. Some of them naturally find their way there. But can we reengineer these to say, maybe, not just break down one component of crude oil, but put in some enzymes that might work on other components? You have these little microbe machines going, all right, what hydrocarbons do you got? I can work with that one, I can work with this one.

But we also have to control the chemistry, because another thing that people have found is that near some of the oil refineries, these microbes are like, oh, yummy. They’ll go into the tubing and piping and stuff and they’ll actually break the pipes and cause an oil spill. We want the microbes where the oil has already spilled, but please do not spill more. Can we understand the enzyme to figure out how to inhibit it? We might have an inhibitor near where there is the tubing and say, okay, you cannot live here on that, but you can live here. Really control where they’re doing that those reactions.

KL: Holy moly. That is really neat chemistry. How do you even go about reengineering these microbes?

CD: We’re starting out looking at the native organism and it can grow on toluene. But if you knock out the enzyme so it can’t really function, then it can’t grow anymore. We’re thinking, okay, we can add stuff and see what makes a good inhibitor and screen for whether the organism can live on the toluene or not. That’s one thing we’re doing. My lab is a structural lab where we really want to look at what the molecules look like. Doing some of these other things of inhibitors stuff is kind of new for us. We’re venturing in uncharted territory. I actually have a lot of undergraduates who are super dedicated to saving the planet. They are just like, I want to work on this project. We have a lot of enthusiasm in the lab for some of these things so hopefully we’ll keep beating on it until it works.

KL: One more research question. Some of your other newer research looks at spare part proteins. What are spare part proteins? How does that all work?

CD: This idea of the spare part protein, it’s actually kind of one of my favorite things. A lot of the cool enzymes that we study, they have metals and they’re sensitive to oxygen, or they have co-factors that are sensitive to oxygen. What that means is that when they are in an oxygenated environment, they’re basically killed. But then when they’re away from oxygen, they’re going strong and they’re happy. Actually, inside the human gut doesn’t have a lot of oxygen in it. A lot of this chemistry is happening there. But sometimes the enzymes can be exposed oxygen.

This one particular system, these enzymes are super cool, they have this built in co-factor, I guess I’ll say that it can do radical-based chemistry. It is an amino acid, a glycine, which is the simplest amino acid known, in part of the protein. It basically forms this radical species. It’s missing a hydrogen atom and a metal co-factor will generate it. When you’ve generated this species, it can just make lots of product, make lots of product. It is a fantastic enzyme, just make a lot of stuff. But when oxygen comes, it just cleaves the whole thing and your protein is literally cut in half and it won’t work anymore. It was discovered, actually a number of years ago, that there was this sort of spare part protein, that once you cut your enzyme in two, it would come and bind and restore the activity. Instead of making a whole new enzyme, nature already had, and was making, all this spare part protein. It was around. If there was oxygen, then it would come in and save the day. We always think of an automobile and you have your spare tire in the back and if something goes wrong, you can add it, and that nature would do this too. Where you have this thing that just could be destroyed by oxygen, that there’s a repair mechanism. There’s an extra little piece that can just bind.

I’m excited about this because this whole family of enzymes, these are ones that work on all of these hydrocarbons that are found in crude oil and things. You worry about doing some of the chemistry, if there’s any oxygen around, it could be problematic, and the chemistry won’t work. But there’s this possibility of these spare part proteins, where if you just make this spare part, you don’t have to worry as much about oxygen. A lot of enzymes that are super useful for industrial purposes that make stuff are sensitive to oxygen. I love the idea of having a backup system for these proteins. It’s like, go ahead, it’s okay, if you get cleaved, we’ll come and fix you right up. But we have a spare, it’s fine.

KL: How is this helping fight the oceans contributing to global warming?

CD: We have one project that is really focused on the ocean and global warming. At least we were looking for the culprit of who, in the upper ocean this time, is releasing methane. We know a lot about how nature makes methane, how microorganisms can make methane, and how other or more organisms can use methane. But those were all these proteins that were super sensitive to oxygen. But researchers discovered that in the part of the ocean that has oxygen, methane was still coming out of there. They’re like, who is making it? Because everyone we know who makes methane is living down deep in the ocean but yet somebody is making methane that we don’t know about.

We worked with Wilfred van der Donk’s lab at the University of Illinois and were able to figure out which enzymes were actually important for making the methane in the upper ocean. In that case, we don’t have a solution for that but we know who they are. I think that’s super important. There are questions that we should all be asking. How many greenhouse gases are coming from the ocean? If the ocean temperature gets warmer, and there’s lots of evidence that it is, will there be more of these microbes when the ocean is warmer? Will they grow more? Do they like living in that warmer temperature? How does the chemistry that they’re doing relate to this? Will they be perhaps making more methane if the ocean becomes more acidic? Or might they make less? How does it relate to other kinds of nutrients that are there?

Another thing that we are very interested in is, let’s make sure we know who all the players are. Because we should be collecting data, we should be thinking about, how does this change affect this other thing? If we don’t know what the other thing is, then we can’t do a good job of modeling it. Unfortunately, I’m sort of afraid that some of our work might suggest that as the oceans get warmer, they’re going to be releasing more greenhouse gases into the environment, which will then make them even warmer. We really do need to be very careful of what we’re releasing into the environment. Because we’re heading down a path where it’s not just the amount that we’re directly putting in, but we’re making changes that are going to then have another effect that’s going to make everything even worse. Now I’m being I’m a bit depressing.

I’m going to remind you that there are really exciting things that we can do to solve these problems. The more information we get, even if sometimes it’s not the happiest information, allows us to be more creative and come up with better solutions. We need lots of smart people thinking about these things. Some of you, if you’re just interested, that’s good enough. I feel like someone’s like, I’m not smart enough to be a scientist. No, no, no, no, no. If you’re interested, you can do this. You can be a scientist, you can be an engineer, come talk to me. We need so many more people to be excited about these problems and come up with solutions. I have an 11-year-old daughter and I want to make sure that the planet is in good shape for her. I need help. I need a lot of help. We need more people coming and thinking about these problems.

KL: I’ll send my two-year-old twins your way as soon as possible because I agree. That’s why I got into coming over to the MIT Energy Initiative as well. This is a really great segue into your teaching. In addition to being a very accomplished researcher, you’re also a celebrated professor here at MIT. Can you talk about how you draw undergraduate students into the fields of biology and chemistry that they may otherwise have felt intimidated by when they were back in high school?

CD: I taught intro level chemistry at MIT from ’99 to 2014. Now I’m teaching intro level biology. I taught today and I’m sitting here wearing a dress that is covered with structures of amino acids, because I was teaching intro biology about amino acids. I try very hard in every lecture to coordinate my outfit with the lecture topic. Today, amino acid, amino acid dress. Yes, you can buy online an amino acid dress.

I start out when I teach, and I confess when I’m teaching chemistry that I didn’t always love chemistry. I tell them about my high school experience. I often like to start with a slide. I say, this is MIT, so there’s a quiz. It’s like, who are these people? I show the slide. They would look and sometimes guess. One of them is me from my college yearbook picture and one of them is Lisa Kudrow, who was my classmate at Vassar College, who is Phoebe on the TV show Friends. I ask, what do you think Lisa Kudrow went to college to study? They say, theater. I say, actually, no, it was biology. What do you think I went to college to study? Well, obviously chemistry or biology. I say, no, actually theatre. What do you think Lisa studied? Well, drama. No, actually, biology. What did I study? They’re like, chemistry? It’s like, yes, I did. One never knows what you’re going to do. There’s a lot of different pathways in life. The last thing I thought I would do when I started at Vassar was chemistry, but I fell in love with chemistry. I say, some of you out there may not have found your love for chemistry yet. You may find it over the course of this chemistry semester. You may find it years later, where you’re trying to do something, of coming up with some new way, alternative energy source, and you realize, I need to talk to chemists. This involves chemistry. But you know what, I took chemistry with Professor Drennan once upon a time and I kind of liked it. I can go back and learn what I need to do and talk to these chemists and together, we can come up with the problem. I don’t know when you’ll find your love for chemistry but you will. Maybe I can get you started now.

I’m also now teaching intro to biology. I’m teaching it with Professor Eric Lander. I like to tell students that Eric Lander, who is head of the Human Genome Project, a celebrated MIT professor, he came to biology through math. All his degrees are in math. He thought about, what is the coolest math problem that I can solve in my life? He said, sequencing the human genome. It’s really a math problem. I’m going to solve that. He came to biology because it had the coolest math problem he could think of. I came to biology because it was the coolest chemistry that I could find. Here we are teaching intro to biology at MIT, a mathematician and a chemist. This is what’s important. You may not have found your love for biology yet. Maybe you will over the course of the semester. Maybe it will be down the road.

But all these problems that are facing the world right now, they need people who understand chemistry and biology. Even if you’re not doing it every day, to understand the fundamentals so you can vote for appropriate politicians, you can write appropriate letters, you can work with the techniques or things that you learn. If you’re doing computer science, trying to solve an energy problem, you might be thinking about designing new materials. You need to know some chemistry for that. Science and engineering can be so interdisciplinary and the biggest problems really require multiple people coming together with different backgrounds, knowing enough to be able to talk and communicate and brainstorm with each other. That’s how we’re going to tackle these very hard things. I’m passionate about teaching because you don’t have to major in biology or chemistry at the end of my course. But I want you to have an appreciation for it and understanding of it so that you can use this fundamental knowledge to solve the world’s problems. Because, again, I have an 11-year-old daughter, and there are a lot of problems. I need you to understand these things so that you can help me solve them.

KL: What were you up to before coming to MIT?

CD: My path has been a little bit unusual. After I graduated from Vassar College as a chemistry major, and yes, I did take some theater classes as well, I decided that I wanted to do something different. I was thinking of grad school but wanted to do something different. I found that I loved teaching. I figured that out as I was going along. I taught high school. I taught high school chemistry, high school physics, high school biology, and high school drama. It was a Quaker boarding school and working hog farm in Iowa. I’ll just set the stage a little: I’m a New Yorker, lived in New Jersey, pretended it was New York, also lived in New York, and Vasser College is in New York. I was never more than an hour and 20 minutes, maybe two hours, from New York City my entire life. Then I graduated from college and I was like, I’m going to move to Iowa and teach at a Quaker boarding school and working hog farm. I liked telling my fellow students at Vassar this because they were also all from New York City and they’re like, Iowa? To them, and to me a little bit, being a true New Yorker, where you know, New York, New Jersey, Pennsylvania, kind of thing, Connecticut, and then there’s sort of something in the middle and then there’s California, and you’ve been to California but you don’t know what’s in the middle. Iowa was just like, super exotic. It’s like, I bet you can’t find it on a map, that’s where I’m going.

I went to Iowa and it was an amazing experience. I loved, loved teaching. Students were really super interesting. Some of them were from Quaker families, a lot of them were from Chicago because that was only about four hours away from the school. Some of them had been in trouble in the public school system, a few of them had gotten involved in drugs and were looking for a fresh start. We had these students come in and we were together and they were in my theater class and in my physics class and it was a really incredible experience. I was there for three years. After that, I felt as I was teaching them that I really wanted to understand how they would use this information that I was teaching to save the world. Because I’m always been very big on saving the world. I was just like, okay, there’s these laws of thermodynamics, and how exactly are people going to use those? I really felt like I didn’t understand enough about what people were doing in research, in chemistry and in biology. What were the big research questions? What were the major goals? I thought, I’ll go to grad school, I’ll learn about the world of research and then I’ll leave with a master’s and I’ll go back and teach high school. This was my grand plan.

I went to the University of Michigan and research turned out to be super fun and cool. I was like, I’ve got to finish my PhD because I am really having a very good time. I had a wonderful advisor, Martha Ludwig, and just was having the best time. People are like, so now are you going to go teach high school with your PhD? It was like, yes, but you know, I’m having a really good time with this research thing so I think I’ll just do a postdoctoral period first. Because there’s this professor at Caltech named Doug Reese and he just studies the coolest things I have ever heard of. He works on nitrogenous, this enzyme that splits that triple bond of nitrogen. How could you not want to work on that first? I’ll just do that, and then I’ll go back and teach high school. While I was there, I had an opportunity to interview at MIT for a faculty position. I just said, how fun is that? To interview for this position. I’ll never get it. Then I’ll go and teach high school. Well, they offered me the job. I said, well, it’s really hard to get tenure at MIT. I’m sure I won’t get that. I’ll just do this and then when I don’t get tenure, then I can go back and teach high school.
It’s been 20 years that I’ve been at MIT. They gave me tenure. I’ve just been having a great time. I have been doing my teaching of undergraduates, not of high school students. I have made videos about all of the amazing research and cool things that are happening at MIT so high school teachers who don’t know how to inspire their students can show them these videos. I feel like I kind of completed my goal, but in a very different way.

KL: Some cool research from your past that I wanted to ask you about, and I think this may have been when you were at Michigan, but please, obviously, correct me. Vitamin B12 and imaging of vitamin B12 and a huge breakthrough that you spearheaded. Can you talk about that?

CD: Vitamin B12 has been called the most beautiful vitamin. I do agree with that. In its natural state, it has the element cobalt in the center of it. It is this beautiful red color, if you just imagine the most beautiful red color. It’s just stunning. Just absolutely a stunning color because of the metal that it has in it. It’s only used by two enzymes in the human body. It’s a very expensive molecule for nature to make. It takes somewhere around 30 enzymes to make one compound of vitamin B12. It’s only used by enzymes that have no other choice. They need that vitamin or they can’t work, so there’s only two.

At the time I was studying it at the University of Michigan, no one knew what the vitamin looked like when it was bound to a protein. In its relevant state being bound to a protein. The initial structure had been solved of it by Dorothy Hodgkins who won a Nobel Prize for her crystallographic work. She was at Oxford and she saw the structure of penicillin, which was really impressive. Then vitamin B12. At the time she solved it, that was the largest thing that had been determined by this technique known as X-ray crystallography. I was very excited to be the first person to show how that molecule bound to a protein. I was able to get that structure in Martha Ludwig’s laboratory in collaboration with Rowena Matthews. I had trained as an undergraduate with Miriam Rossi, who had trained with someone who had trained with Dorothy Hodgkins. There was this generation, these female X-ray crystallography line that worked on vitamin B12, so that was an extremely cool heritage to have as well.

We got the structure and it had actually the vitamin change shape. It had rearranged when it was bound to the protein. It was a really big surprise at the time. That was, for me, it was such an exciting result. I was like, how can I give up doing this research? These proteins are teeny, tiny things inside your cells and there are these techniques that let you figure out what they look like. Once you see what they look like and where their pieces are, you can figure out how they work. It’s like, I’ve got to see a lot of these. There’s a lot out there, we don’t know what they look like, and I just want to know, especially the ones that do the cool chemistry. I really want to apply these techniques of X-ray crystallography and now cryo electron microscopy. Which we have two wonderful instruments at the MIT.nano building at MIT that allow you to much more easily visualize these tiny little molecules and understand what they do. It’s the most exciting time to be working in this area. The technique development is huge. We can now have many more discoveries of figuring out what these proteins look like and how they work. Such an exciting time to be doing biology. I cannot tell you, it is so exciting.

KL: I am going to ask a question, and you can totally say it’s too personal, related to your dyslexia. How is being dyslexic? Or how has being dyslexic affected your career in science, if any? I would imagine it would be difficult when you’re looking at the formulas, to reconcile.

CD: I was diagnosed as being dyslexic, I think it was about first grade. When I just wasn’t learning to read and my teachers were looking at me like, she’s a very articulate kid. She likes adults. She’s chatting about everything. She’s knowledgeable about the world. Why can this girl not learn how to read? I finally figured out in sixth grade how to read. The way that I read, and I don’t know whether multiple people with dyslexia do this, but I memorized the shapes of the words. I don’t read by sounding out, which I understand is what normal people do. I look at the shape of the word and go, I know that word, that word, say, is “should”. I look at another word and it’s like, oh, I see the shape of that word, that’s “showed”. But some words that have similar shapes are a little confusing to me. Sometimes I’ll write the wrong word down. But I memorized enough and I had memorized the shape and then I would know what that word was and how that word sounded. I had separate memories and then I’d have to link. I had to translate everything as I’m reading.

I wasn’t supposed to be able to graduate from high school, according to the folks who diagnosed me, they said my dyslexia was severe enough that I would have a lot of trouble in school. My parents decided, to their credit, to not inform me that I couldn’t graduate from high school until after I had graduated from high school, which was very wise on their part. I went to college and I hid my dyslexia and I just studied harder, hoping that if I lost points, because I flipped numbers around or whatever, that I would just know it better than other people, so I wouldn’t lose any points except for the ones that were due to my dyslexia.

But in my research, I actually think that my learning, memorizing shapes and thinking about shapes and being very good at shape recognition, is actually a huge plus. Because the data that we get, we don’t actually get to see directly the atoms. We see what we call maps of electron density. What we get out of these different techniques, we know where the electrons are. Basically, there are atoms there but we don’t know which one they are, so we have to build a model into it. We say, I know what this amino acid looks like, I know what this amino acid looks like, I’m looking at it and going, I recognize this shape, that’s that amino acid. I recognize this shape, that’s this amino acid. Sometimes a graduate student of mine will be sitting and just looking at these maps and they’re like, I don’t know what’s happening here. Is it going this way? Is this going this way? What is this part due to? What is happening? Sometimes they’ll be like, it goes up here and down here. No, no, not through there, it goes over here. This is how it’s connected. They just look at me, it’s like, how did you see that? It’s like, I don’t know, I just saw that this is the way it is. I have practice looking at it. But I think that since I was learning how to read in first grade by my own figuring it out on my own what worked for me, I just became super good at recognizing shapes. Now what I do, I’m better at it because I’m dyslexic. I think instead of “disabled” people really should say “different-abled”, because you are different-abled when you have a disability.

KL: Thank you. I was just imagining people listening, who may be avoiding some of these classes, because they’re dyslexic themselves and have gotten messages that this isn’t possible for you. This isn’t a career path. I think it’s just so great that there’s proof that there is.

CD: I actually know a lot of people with dyslexia in science. I think it’s a great area. Maybe your brain works slightly differently, but we like that in science. We want people who are out of the box, thinking about problems, and are able to see things and put things together maybe in a slightly different way. No one should ever rule anything out. If you have a passion, you can figure out a way to do it. You may be better at some of these things then, then someone who’s “normal”.

KL: What’s next for you?

CD: What’s next for me? Right now, I feel like next is the next lecture in intro to bio. I think at the beginning of the semester, it’s always just one day at a time, one day at a time. But bigger picture, let me try to remember what’s going to happen after I get these lectures together.

I’m actually really excited about my research program right now. I have a fantastic group of individuals. I’ve been very active in some of the summer programs that MIT has. MIT MSRP program, which brings in students from underrepresented groups for summer research. I’ve had some spectacular undergrad students come through the program. I’ve recruited them back to be graduate students at MIT and then recruited them into my lab. I have this fantastic group of a really diverse lab full of individuals who are ready to tackle this world and solve important problems.
I’m very excited about this new technique, well, it’s not a new technique medicine, of cryo electron microscopy. It’s an old technique that has undergone a revolution. Because there’s just new methodology and new hardware and software. What you’re able to do with it now, it just blows my mind. With this group of students and this new technology… there are problems that I decided were too hard that now we’re going to go do. Some of them are definitely related to energy. I’m very interested in the complexes that involve carbon dioxide metabolism and also methane production. Some of these are just huge, multi, multi enzymes, big enzymes in these giant complexes. I think in the past, there was just no way we were going to get structural information on them. Now we can.

KL: Sounds really, really exciting. I can’t wait to see what comes out of your lab in the next couple of years. Next seven years.

CD: Seven years.

KL: With your HHMI renewal.

CD: Yes.

KL: Where can people keep up with your research?

CD: We try to keep our website, the Drennan Lab website, somewhat up to date. Maybe it’s not too bad. We enjoy working with the folks at MIT News and also Energy Futures and if we have something that we think is going to be of interest, let them know that a paper is coming out. I recently got arm-twisted onto Twitter. I have a Twitter account where I try to let people know what’s happening in the lab. I was in a meeting of the American Chemical Society. My husband is a scientist, he’s a chemist. My poor 11-year-old daughter, two chemist parents. She’s an only child. She’s like, I am outnumbered by these chemists. We’re both kind of biochemists so it’s like, man. But he was just very active on Twitter and people were telling me things that I didn’t know about my husband. How do you not know that he wrote about it on Twitter? It’s like, I better get on Twitter so I can know what my husband is doing.

KL: What is your Twitter handle?

CD: @drennan_lab.

KL: I’ll be following you. Your husband’s going to start learning about your stuff from Twitter as well. Thank you so much for being here. It was such a pleasure to speak with you, Cathy.

CD: It’s been a real pleasure. Thank you very much.


Catherine Drennan says nothing in her job thrills her more than the process of discovery. But Drennan, a professor of biology and chemistry, is not referring to her landmark research on protein structures that could play a major role in reducing the world’s waste carbons.

“Really the most exciting thing for me is watching my students ask good questions, problem-solve, and then do something spectacular with what they’ve learned,” she says.

For Drennan, research and teaching are complementary passions, both flowing from a deep sense of “moral responsibility.” Everyone, she says, “should do something, based on their skill set, to make some kind of contribution.”

Drennan’s own research portfolio attests to this sense of mission. Since her arrival at MIT 20 years ago, she has focused on characterizing and harnessing metal-containing enzymes that catalyze complex chemical reactions, including those that break down carbon compounds.

She got her start in the field as a graduate student at the University of Michigan, where she became captivated by vitamin B12. This very large vitamin contains cobalt and is vital for amino acid metabolism, the proper formation of the spinal cord, and prevention of certain kinds of anemia. Bound to proteins in food, B12 is released during digestion.

“Back then, people were suggesting how B12-dependent enzymatic reactions worked, and I wondered how they could be right if they didn’t know what B12-dependent enzymes looked like,” she recalls. “I realized I needed to figure out how B12 is bound to protein to really understand what was going on.”

Drennan seized on X-ray crystallography as a way to visualize molecular structures. Using this technique, which involves bouncing X-ray beams off a crystallized sample of a protein of interest, she figured out how vitamin B12 is bound to a protein molecule.

“No one had previously been successful using this method to obtain a B12-bound protein structure, which turned out to be gorgeous, with a protein fold surrounding a novel configuration of the cofactor,” says Drennan.

Carbon-loving microbes show the way

These studies of B12 led directly to Drennan’s one-carbon work. “Metallocofactors such as B12 are important not just medically, but in environmental processes,” she says. “Many microbes that live on carbon monoxide, carbon dioxide, or methane—eating carbon waste or transforming carbon—use metal-containing enzymes in their metabolic pathways, and it seemed like a natural extension to investigate them.”

Some of Drennan’s earliest work in this area, dating from the early 2000s, revealed a cluster of iron, nickel, and sulfur atoms at the center of the enzyme carbon monoxide dehydrogenase (CODH). This so-called C-cluster serves hungry microbes, allowing them to “eat” carbon monoxide and carbon dioxide (CO2).

Recent experiments by Drennan analyzing the structure of the C-cluster-containing enzyme CODH showed that in response to oxygen, it can change configurations, with sulfur, iron, and nickel atoms cartwheeling into different positions. Scientists looking for new avenues to reduce greenhouse gases took note of this discovery. CODH, suggested Drennan, might prove an effective tool for converting waste CO2 into a less environmentally destructive compound, such as acetate, which might also be used for industrial purposes.

Drennan has also been investigating the biochemical pathways by which microbes break down hydrocarbon byproducts of crude oil production, such as toluene, an environmental pollutant.

“It’s really hard chemistry, but we’d like to put together a family of enzymes to work on all kinds of hydrocarbons, which would give us a lot of potential for cleaning up a range of oil spills,” she says.

The threat of climate change has increasingly galvanized Drennan’s research, propelling her toward new targets. A 2017 study she co-authored in Science detailed a previously unknown enzyme pathway in ocean microbes that leads to the production of methane, a formidable greenhouse gas: “I’m worried the ocean will make a lot more methane as the world warms,” she says.

Drennan hopes her work may soon help to reduce the planet’s greenhouse gas burden. Commercial firms have begun using the enzyme pathways that she studies, in one instance employing a proprietary microbe to capture CO2 produced during steel production—before it is released into the atmosphere—and convert it into ethanol.

“Reengineering microbes so that enzymes take not just a little but a lot of CO2 out of the environment—this is an area I’m very excited about,” says Drennan.


Professor Catherine Drennan (right) and former Undergraduate Research Opportunities Program (UROP) student Ben Bell ’14 adjust a crystal for an X-ray diffraction experiment aimed at determining a structure of a metalloprotein at atomic resolution. Photo: James Kegley

Creating a meaningful life in the sciences

At MIT, she has found an increasingly warm welcome for her efforts to address the climate challenge. “There’s been a shift in the past decade or so, with more students focused on research that allows us to fuel the planet without destroying it,” she says.

In Drennan’s lab, a postdoc, Mary Andorfer, and a sophomore, Phoebe Li, are currently working to inhibit an enzyme present in an oil-consuming microbe whose unfortunate residence in refinery pipes leads to erosion and spills. “They are really excited about this research from the environmental perspective and even made a video about their microorganism,” says Drennan.

Drennan delights in this kind of enthusiasm for science. In high school, she thought chemistry was dry and dull, with no relevance to real-world problems. It wasn’t until college that she “saw chemistry as cool.”

The deeper she delved into the properties and processes of biological organisms, the more possibilities she found. X-ray crystallography offered a perfect platform for exploration. “Oh, what fun to tell the story about a three-dimensional structure—why it is interesting, what it does based on its form,” says Drennan.

The elements that excite Drennan about research in structural biology—capturing stunning images, discerning connections among biological systems, and telling stories—come into play in her teaching. In 2006, she received a $1 million grant from the Howard Hughes Medical Institute (HHMI) for her educational initiatives that use inventive visual tools to engage undergraduates in chemistry and biology. She is both an HHMI investigator and an HHMI professor, recognition of her parallel accomplishments in research and teaching, as well as a 2015 MacVicar Faculty Fellow for her sustained contribution to the education of undergraduates at MIT.

Drennan attempts to reach MIT students early. She taught introductory chemistry classes from 1999 to 2014, and in fall 2018 taught her first introductory biology class.

“I see a lot of undergraduates majoring in computer science, and I want to convince them of the value of these disciplines,” she says. “I tell them they will need chemistry and biology fundamentals to solve important problems someday.”

Drennan happily migrates among many disciplines, learning as she goes. It’s a lesson she hopes her students will absorb. “I want them to visualize the world of science and show what they can do,” she says. “Research takes you in different directions, and we need to bring the way we teach more in line with our research.”

She has high expectations for her students. “They’ll go out in the world as great teachers and researchers,” Drennan says. “But it’s most important that they be good human beings, taking care of other people, asking what they can do to make the world a better place.”


This article appears in the issue of Energy Futures.


Climate & Environment Education
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