A Fascinating World of Viruses with Microbiologist Hannah Gavin

SPEAKERS

Hannah Gavin, Jennifer Berglund

 

Jennifer Berglund 00:04

Welcome to HMSC Connects! where we go behind the scenes of four Harvard museums to explore the connections between us, our big, beautiful world, and even what lies beyond. My name is Jennifer Berglund, part of the exhibits team here at the Harvard Museums of Science and Culture. And I'll be your host. Today, I'm speaking with Hannah Gavin, a microbiologist and educator who researches viruses, and also manages Harvard's Microbial Sciences Initiative. She studies ocean bacteriophages, or viruses that infect bacteria. I wanted to ask her about that, and what it's like to study something we can't see with the naked eye. Here she is. Hannah, Gavin, welcome to the show.

 

Hannah Gavin 01:09

Hi, thanks for having me.

 

Jennifer Berglund 01:15

You study bacteriophages, which are viruses that attack bacteria. Tell me how they work, and what specifically are you trying to learn from them?

 

Hannah Gavin 01:26

Yeah, so bacteriophages, or "eaters of bacteria"--that's what the name means--are these viruses that are specific for bacteria. So there are viruses that infect pretty much any type of cellular life, but these viruses are specific for bacteria. So if we were to, you know, put them onto or in a human, they wouldn't infect human cells at all, they just attack the bacteria. The lifecycle of a bacteriophage is essentially, that there's this viral particle, very tiny, and it attaches to the surface of a bacteria, and then it injects its DNA or RNA into that bacterial cell, and it then uses the cellular machinery to replicate. So viruses are essentially parasites, they can't replicate by themselves, which is why they aren't technically considered alive, but they replicate using the help of a cell, and so they make more viral particles, phage particles, inside a bacterial cell, and then ultimately, there's this sort of lethal microscopic burst where the new phage particles burst out of the bacteria, killing it, obviously, and then go on to infect more neighboring cells. So there are lots of things you can imagine in that process that would be interesting to try to study. There are lots of different types of phages too, and so a lot of scientists are asking, how do they attach the bacteria? What sorts of structures do they use to attach to the bacteria? How do they replicate inside the bacterial cell? And some of this, for some phages, is known, but there's a lot of unknowns too. And then the flip side of that, really, is how to bacteria resist phage infection? How did they evolve to become resistant to that, too?

 

Jennifer Berglund 03:24

Yeah, and that's really interesting because the bacteriophages and bacteria have been interacting with each other almost since the beginning of life. There's sort of been this evolutionary arms race between the two, where viruses are getting better and better at infecting bacteria, and bacteria are getting better and better at avoiding viral infection.

 

Hannah Gavin 03:48

Absolutely. It's not static. It's it's a really dynamic process, and because they're both capable of evolution--it's because they're both capable of evolution. So you have bacteria evolving and viruses evolving in response, and vice versa.

 

Jennifer Berglund 04:06

The interesting thing about that is by studying these adaptations and bacteria, or their responses to viruses and vice versa, you can sort of develop some sort of understanding of how we might utilize those responses in our own scientific experimentation and our own development of drugs.

 

Hannah Gavin 04:27

Oh, absolutely. I think that there are a few different really big drivers behind asking questions related to phages and bacteria are really, really anything that might be considered basic science in the lab, and one of those is for curiosity, and humans wanting to learn more and wanting to have a conceptual understanding of how the world works, but also one of them is potential application and potentially learning something that might benefit society and humanity and figuring out how we can apply what's happening in nature, and what, as you point out, has been happening for so long. For so much longer than we, as humans have been studying it. Many people will say that biology has had a better chance to get it right than we do because it's been happening for so long.

 

Jennifer Berglund 05:14

You use viruses that were gathered from seawater.

 

Hannah Gavin 05:18

Yes.

 

Jennifer Berglund 05:18

Correct? So ocean viruses? How do you study these viruses in the lab? It seems like it must be really tricky to study something you can't see.

 

Hannah Gavin 05:28

Yeah, so viruses, by nature are very, very tiny, usually tinier than bacteria are. So I think it's a really natural assumption for anybody doing any sort of microbiology that we're using microscopes a lot, and certainly many microbiologists use microscopes in their work. But actually, a lot of us don't, and that's because there are processes that you can observe, or basically indirect evidence that you can use for detecting your organism or microbe of interest. And so, for phages, that's really what we do. We can use the fact that phages kill bacteria to detect their presence in many ways, and so a basic outline of an experiment would be that I would grow some bacteria because, as I mentioned before, the viruses need the bacteria to replicate, and so I grow some bacteria, and then add phages to bacteria. And then depending on the experiment that I'm doing, the outcome that I'm looking for, I can, you know, use that phage and bacteria combination to look for some sort of outcome, and count, essentially, how many phages come out of a single bacterial cell, or were in a given sample, or how they interact with the bacteria that we're studying. So really, we're just looking for evidence of the phages being there by the fact that they've killed bacteria.

 

Jennifer Berglund 06:44

What does that look like?

 

Hannah Gavin 06:46

I use a lot of petri dishes, and I do a lot of counting, which is not super glamorous, but it's honest, it's. I think that a lot of science just involves a lot of counting things. You're basically asking a question, and then quantifying some sort of outcome. You know, I'll grow, streak out the bacteria onto a petri dish using a nutrient jelly called agar, and then you get colonies, or these dots of individual bacteria, and then I can grow those in a liquid medium and we can detect the presence of bacteria growing because the media will go from being clear to being really opaque, or what we call turbid. And then I can take those bacteria and combine them with phage, and then usually that involves putting them back on a plate, on a petri dish with agar. And the plate, when it's covered in bacteria, will also become opaque because there's so many bacteria there, that we call it a lawn, but wherever a phage landed, a clear spot will develop. And that's because, initially, you can't see where the phage has landed, but as it multiplies, and as it kills bacteria, it will develop a spot on the plate where it's killing. And actually, those spots grow over time, too, because the phage is moving outward and propagating. And so you get these zones of clearance on the plate, and they're basically a clear spot you can see through because they've killed all the bacterias, so it's not opaque or turbid anymore.

 

Jennifer Berglund 08:05

So it's kind of like flying over a forest that's been infected by some sort of blight or something like that, where, like, you would fly over it, and you would see green, and then there'd be spots of dead trees that have been infected by some sort of blight.

 

Hannah Gavin 08:18

Yeah, that's a really good analogy is that if you were to look down, you'd see a cluster or brown trees, or a cluster of trees where all the leaves have fallen off, yeah. That's a that's a great visualization.

 

Jennifer Berglund 08:28

So then what do you do? So you find these clear areas, then how do you go in and capture the virus? And then what do you do?

 

Hannah Gavin 08:35

Sometimes counting is the outcome that we're looking for. Sometimes that lets me know, the answer that I needed, you know, I can count those clear spots, the zones of clearance on a plate, and say, "okay, great. Now I can back-calculate how many phages there were in this sample? That's my answer." But oftentimes, we are wanting to then isolate the phage, and so I took a tip that would be used on a pipette and use it to puncture the plate, and collect this small plug of agar covered in bacteria and phage, and I basically can puncture through it and take this little, kind of akin to a soil core, except very small. And so that way we can isolate the phage that are there.

 

Jennifer Berglund 09:16

So you sort of like cookie-cut a bit out?

 

Hannah Gavin 09:19

Yeah, exactly.

 

Jennifer Berglund 09:20

You take the cookie out, and you can isolate it.

 

Hannah Gavin 09:22

Yeah. A cookie-cutter, or like, I have biscuit-cutters at home that you can punch down into. Yeah, exactly.

 

Jennifer Berglund 09:27

Yeah. And then so you can isolate the virus that way, nd then and then what do you do?

 

Hannah Gavin 09:33

And then we can do a couple of different outcomes. Maybe I'll grow it because I want to then use it for subsequent experiments, especially if I'm working from a sample at the beginning that wasn't homogenous. So maybe there are lots of different viruses in an original sample, and I'm wanting to focus on one so I could grow more of it. Oftentimes, we also sequence them. And so we're in an age where genetic and genomic sequencing is, relative to what it was in the past, fast and cheap, and so we do a lot of sequencing, and that allows us to characterize the viruses not only on their characteristics, not only on how quickly they kill bacteria, how many viruses come out of a given bacterial cell, but also on the basis of their genetic content. We're in the process of doing that right now. We're going to sequence some so that we can then go back and look in other samples and see how prevalent they are, whether they're there, how many copies of them, that sort of thing. And then having the sequence also allows you to compare and contrast them to other viruses, which is really helpful, especially because scientists think that we've really only scratched the surface in terms of viral diversity, and so it's really helpful to be able to say, Oh, this gene, and this virus seems to be similar to these other viruses. This gene we haven't really seen before, or this arrangement of genes we haven't seen before. So being able to compare and contrast them to other existing sequences is also really helpful.

 

Jennifer Berglund 11:02

Okay, interesting. So there's sort of an evolutionary component to this too by sort of understanding relationships between viruses.

 

Hannah Gavin 11:10

Yeah.

 

Jennifer Berglund 11:14

Let's talk about ocean viruses and why they're interesting. You know, first off, talk about just the sheer number of viruses in the ocean, which I think is pretty fascinating.

 

Hannah Gavin 11:24

It's huge. Viruses are the single most abundant biological entity in the ocean. And

 

Jennifer Berglund 11:31

That's crazy!

 

Hannah Gavin 11:32

It's just, the numbers are millions per milliliter of seawater. It's neat to know that, and then it's also neat to see it People have taken samples of seawater and then stained them using dyes, fluorescent dyes that attach to DNA, and then looked at the result under a microscope, and it actually looks sort of galaxy-like, or at least, what I imagine the galaxy to look like Maybe sort of the Milky Way. You have different bursts where you can see these different sizes of organisms or microbes, and they're just tremendously abundant. It's pretty amazing.

 

Jennifer Berglund 12:08

Why are they so abundant in the ocean?

 

Hannah Gavin 12:11

Because they can be in the sense that they're, they're sort of growing to the nutrient capacity that is allowed by the ocean, and there's some sort of cap on that, some sort of carrying capacity that any ecosystem has, but they're in an environment that they've been very successful to adapting to, and to, to replicating in, and also to interacting in. And so they're just really, they're just really flourishing there.

 

Jennifer Berglund 12:39

It's wild to think about, you know, this whole world that exists within our own world that we can't see or really detect without really sophisticated science. Absolutely. No, it's just mind-boggling. Why do you think it's important to study these viruses that are found in the ocean?

 

Hannah Gavin 12:59

I would say there are a few different aspects to that, and we touched on this a little bit earlier. I think, upon realizing this, upon getting to look at an ocean sample, or a pond sample, or soil sample, and realizing that there's life happening that maybe our naked eyes isn't privy to, I think it's really natural to be really curious about that and to want to understand how it works. So at some level, because it's fascinating. And then at a more applied level, microbes are tremendously important for a few different processes, and I guess I'll talk about viruses specifically, but when we think about the ocean, viruses are helping cycle a lot of nutrients because of their capacity to kill microbes, to kill bacteria and other microscopic organisms in the ocean. And you might imagine that that would be a negative thing, and we hear a virus, or killing, or those are, those have negative connotations, but realistically, they're helping carbon and nitrogen and phosphorus and all these sorts of essential elements and molecules to be cycled and recycled, and by killing bacteria, they're releasing a lot of those nutrients, and then they get taken up into other organisms, and that's an ongoing, cyclical process.

 

Jennifer Berglund 14:15

So that's pretty cool because that directly relates to something that really matters to us, which is global climate change, for example. So, it's really these bacteria, and also these algae, essentially, that absorb the vast majority of the carbon from our atmosphere. And they take that carbon, they turn it into nutrients that are consumed by other critters in the ocean, and subsequently transported to the bottom of the ocean. And so by taking that carbon out of the atmosphere, that's literally what makes our planet habitable. So viruses, you could argue, are directly responsible for making our planet habitable. Is that fair?

 

Hannah Gavin 14:59

I think it is. I think it is, yeah.

 

Jennifer Berglund 15:02

Okay, Mind blown! Did you always know that you wanted to be a scientist?

 

Hannah Gavin 15:15

No. I definitely remember being fascinated by science, starting maybe in middle school. I had a great life science class, and that was when I first realized that things were made out of cells, which was definitely a pretty life-altering moment. I think I realized that there was this whole level of life happening that I didn't see, simply because our eyes can't see it normally, but realize that it was happening nonetheless, regardless of whether or not I could observe it on the day to day, and it was influencing me anyway. So I definitely remember being being interested by science from that point forward, and liking how it changed my perspective on things, like on the apple that I ate as an after school snack, or on trees, or, or other aspects of nature. But I definitely didn't know from that moment on that I was going to study science. I went through a few different iterations of hopeful career paths, I was going to be a dolphin trainer at one point. And

 

Jennifer Berglund 16:14

Like so many of us.

 

Hannah Gavin 16:15

Then I was gonna be a chef at one point, that was a fun. Or a restauranteur. Then, late in high school, I had a really fantastic chemistry class. So then going into college, I thought, okay, this seems pretty sweet, maybe I'll study chemistry and teach, and then I got hooked on research while I was in college. That was just so much fun, hands-on research. And

 

Jennifer Berglund 16:17

What kind of research did you do?

 

Hannah Gavin 16:26

I was studying the gut and how high fat diets impact the gut, basically, and then maybe our risk for diseases. I think digestion is a really interesting aspect of physiology and biology. There's so much happening in the gut.

 

Jennifer Berglund 16:57

Where did you go from there?

 

Hannah Gavin 16:58

Well, at that point, I still consider myself a pretty human-centric biologist, I thought that, you know, human health was where it was at. But right around that time is when we as scientific community, we as a human community, started appreciating and understanding the complexity of the gut microbiome. And so suddenly, this organ that I had been studying wasn't just human cells anymore. It was also this incredibly complex milieu of microbes, and genes and and processes that were going on. So that sort of sparked my awareness or renewed awareness of microbes, and I went on to graduate school, and even then wasn't really committed yet to microbiology. II tried three different labs, all centered around gut health, and one of them was studying colon cancer, one of them was studying gut immunology, and one of them was studying a bacteria that infected the gut, and that was the first time I'd really worked with microbes, and it was fun They grow quickly, or at least the microbes that I was using, they grow quickly, and you can do various manipulations, and it was becoming more clear every day that microbes were also really important to human health, too, so there's this very clear tie to human health, and I just got sold. Sold on microbes.

 

Jennifer Berglund 18:25

It's funny, you talk to people who do things like study lions, or rhinos, or things like that, like the charismatic megafauna. That, you know, so many people get into biology and behavioral ecology for, and it ends up kind of being a little boring because you end up sitting around for long periods of time, waiting for the moment when you can get the data you need. You know? Or, or it's like, hard to find what you need to find to get the data you need. And microbial sciences are, like, in some ways, so much more exciting because things are happening constantly. There's so much action.

 

Hannah Gavin 19:07

That's a really good point. The timescales on a microbial life, or a replication cycle, are just pretty astounding. Astoundingly fast for a lot of them.

 

Jennifer Berglund 19:16

Yeah. So it's, like really easy to get a lot of data really fast, and and figure out what's going on.

 

Hannah Gavin 19:21

Mm hmm. Yeah, anybody who listens to this and studies tuberculosis though is gonna really

 

Jennifer Berglund 19:26

Oh really? Why is that?

 

Hannah Gavin 19:27

It takes weeks to grow. Whereas the a lot of the bacteria I study, they're in the Vibrio genus, and they they multiply really quickly, you know, like, double in half an hour type of situation. So

 

Jennifer Berglund 19:41

Oh, man.

 

Hannah Gavin 19:42

Maybe I'm spoiled in terms of some microbiologists, but relative to anybody studying something that takes 15 years to mature, or decades to mature. It's real fast. Yeah.

 

Jennifer Berglund 19:54

So how did you get to ocean viruses?

 

Hannah Gavin 19:56

Oh, yeah. Well, the the gut pathogen that I was studying This bacteria that infects the human gut, it gets there via oysters, or shellfish, that people are eating. And so for a few years, I studied a toxin that the bacteria produce, and how that harms that gut lining, and really interesting stuff, and then towards the end of my graduate work, I started thinking more about why that toxin had evolved in the first place, and in order to think about those things, I had to think about the fact that this bacteria was evolving in the ocean. And even though it's really unfortunate that humans get exposed to it by eating raw shellfish, the bacteria didn't evolve to do that. It's an incidental infection. They actually, they evolved to compete and exist and thrive and survive in the ocean. And so then I started thinking about how that's true for a lot of microbes, as, as we mentioned, there are just so many microbes in the ocean. And that really, there's just a huge abundance of microbial life happening there, and evolution. That's where a lot of the action's happening. One of the big pressures on any bacteria living in the ocean is viral predation, is phage predation. And so that's how I eventually got to, to what I'm studying now,

 

Jennifer Berglund 21:12

It's interesting that, as a child, you went from wanting to be a dolphin trainer to a chef, because, you know, in some ways, you're kind of doing all of that right now. And and an educator, right? Like, doing science in the lab is a lot like cooking, right?

 

Hannah Gavin 21:27

It is. It is. They're hands-on, there are recipes, aka protocols. Yeah, completely.

 

Jennifer Berglund 21:32

Yeah, you're training bacteria and viruses. And you're also involved in a lot of museum work and education, so you found this way to combine all of your interests, which I think is really cool.

 

Hannah Gavin 21:42

I really have. I feel so fortunate. And I think it's also fun to reflect on that. It's not something I do every day, but it's fun talking to you about it, and reflecting on how bits and pieces of those thoughts or dreams or aspirations along the way have puzzle pieced together into what I'm doing now.

 

Jennifer Berglund 21:59

In addition to your work as a scientist, you also volunteer at the museum, and you're a program manager for the Microbial Sciences Initiative, MSI, at Harvard. So tell me about the work you do for each, and what you hope to inspire in others in doing that work.

 

Hannah Gavin 22:18

I hope it's obvious from talking up to this point that I really enjoy being in the lab, and hands on research is a lot of fun, but I also love talking to people about research, and I love facilitating other people learning about various aspects of science or biology. And there are numerous different forms that that takes. Some of its in the classroom, some of its at conferences, some of its in random meetings in hallways, and some of its in places like museums. So, I love being involved in all of those different facets. MSI is an intellectual epicenter for microbiology in New England, and it came out of the realization that even at one university at Harvard, microbiology was happening in different departments, in different programs, in different campuses, and that sometimes that's a barrier to people knowing what's happening with other microbiologists, even at the same university. So it was founded on the idea that those microbial scientists needed the opportunity to communicate and collaborate, and that there should be some sort of central organizing hub to do that. And so that's ultimately what we're trying to do at Harvard, but also throughout New England, and particularly now that things have gone remote, even nationally, and internationally bringing together people from all sorts of different microbial science communities from different physical places. So that takes the form of organizing seminars and symposia, opportunities for people to get to know each other's research, to present their research, to talk about it. I work with undergraduate students during the summer to organize a fellowship program where they get to do research, and we also get together to talk about applied microbiology. We brew some kombucha. We talk about professional development Then, among the different outreach efforts that MSI has, one has been this connection to the microbial life exhibit at the Museum, which started long before I came, but when I arrived in, actually, this is a funny story. When I arrived in Boston, the microbial life exhibit was set to only be available for a few more weeks, and so I put it on my list of things I had to do in my first few weeks in the area.

 

Jennifer Berglund 24:34

That's so funny!

 

Hannah Gavin 24:35

Because it's just, as you probably know, microbes don't really get spots in most museums, despite being so intimately connected to the natural history, the history of our planet, the history of our species. It's because they're so small and not obvious that we're interacting with them. They, for many years, haven't had much of a place in a museum, and so I put it on my list of things to do, went to the exhibit, and thought that was great. I've seen that, I've done that, thank goodness I made it in time. And then, when the exhibit got extended, I started volunteering at the demo station, showing people things through the microscope, talking about fermented foods, talking about different sorts of accessible microbes. Thankfully, that exhibit is still around, so I'm still doing that, or at least still when we're in person and still chatting about microbes in some other capacities to.

 

Jennifer Berglund 25:30

So what do you hope to inspire in those kids and those visitors?

 

Hannah Gavin 25:34

Hmm. I don't know, thinking back to the realization for me that things were made out of cells, and, whoa, my apple is made out of cells, and all of life is layers that I can't see on a daily basis, but they're there, and they're happening. I think they've really changed the way that I go about my day and go about my life. I think that appreciation, I hope some people walk away with and maybe a little bit of curiosity to explore some aspect that strikes them, whether it's making some sort of fermented food at home, or just reading about the way that life works, and at this level, at the scale that we can't normally see.

 

Jennifer Berglund 26:14

Why do you think it's essential we develop an understanding of the microbial world, which is a place that's largely invisible to us?

 

Hannah Gavin 26:23

It is invisible to us, but it has a tremendous impact on our planet. There is no ecosystem, almost no process that I can think of, that is not influenced by microbes, whether or not we can see it. The more we look into, the more we find. Whether we're looking to wrangle or harness some sort of process that a microbe has already come up with for our collective benefit, or just looking to be awed, in either case. microbial life can do it for you.

 

Jennifer Berglund 27:05

Hannah Gavin, thank you so much! This has been wonderful.

 

Hannah Gavin 27:08

It's been great to talk to you. Thank you so much.

 

Jennifer Berglund 27:20

Today's HMSC Connects! Podcast was produced by me, Jennifer Berglund, and the Harvard Museums of Science and Culture. Special thanks to Hannah Gavin and Harvard's Microbial Sciences Initiative for their wisdom and expertise. By the way, stay tuned for a new online exhibit spotlight on viruses that we worked on with Hannah, which we'll release soon on the HMSC Connects! website. Also, just to let you know, we're taking a little bit of a break from the podcast for the holiday season, but we'll be back in the middle of January next year. Thanks so much for listening! If you like today's podcast, please subscribe on Apple Podcasts, Spotify, Podbean, or wherever you get your podcasts. See you next year!

 

Transcribed by https://otter.ai