Announcer:
Welcome to the Salk Institute’s Where Cures Begin podcast where scientists talk about breakthrough discoveries with your hosts Allie Akmal and Brittany Fair.

Brittany Fair
So I’m here today with Dr. Molly Matty. Dr Matty is a postdoctoral fellow in the lab of Associate Professor Shrek Chalasani, where she studies how bacteria affect the behavior and brain signaling of worms. Dr Matty, welcome to Where Cures Begin.

Molly Matty
Thank you. I’m happy to be here.

Brittany Fair
So these tiny worms that you study are called nematodes. How big are these nematodes exactly?

Molly Matty
So the adult nematode that we work with, Caenorhabditis elegans is about one millimeter long.

Brittany Fair
That’s really small.

Molly Matty
It is very small. We do all of our experiments under a microscope.

Brittany Fair
I was going to say, can you even see them?

Molly Matty
You can, uh, when you have them on a plate and they’re adults, you can see it looks like, um, half of an eyelash on a plate.

Brittany Fair
And you know, why do nematodes make a good scientific model?

Molly Matty
Yeah, so there’s a bunch of reasons. Uh, one of the reasons that I really like that I don’t work on at all is that we know, we being scientists, know where each and every one of their cells came from. Uh, so we have a lineage tree of every single cell and there’s about a thousand cells in the whole adult animal. So about 300 of them are neurons, 20 of them are intestinal cells. And then there’s, you know, some, some muscles and other things going on of course. But, um, we kind of joke that they’re just a ball of neurons and a gut and a gonad, but we know, we know where each and everyone of those cells came from. And from a single cell stage all the way up to its adult stage. So it’s really good for studying developmental genetics and developmental biology.

But the other thing that’s really cool is that they’re transparent so you can see everything going on inside their body at all times. If you label neurons with trans genes for a calcium indicator, whenever calcium enters a cell, it’ll glow bright green, and we can use that to indicate neuronal activity. So you put a microscope on these transgenic worms and they’ll glow green whenever a signal is sent from one neuron to another.

Brittany Fair
Okay. And is this what you’re studying?

Molly Matty
Eventually? I will get there. Yeah. So the Chalasani lab is really great at studying these neural circuits. So how one neuron signals to another, to another to eventually turn into a behavior and you just put the microscope over to that space and maybe you expose them to an odor that they like and you can see which neurons light up and then you can expose them to an odor that they don’t like and you see which neurons light up.

So that makes it an excellent model for studying neurobiology, which is what we do in the lab. Uh, another really cool thing about the worm that I’m using in my postdoctoral work is they eat bacteria.

Brittany Fair
Okay?

Molly Matty
That’s their food source. So these nematodes that we work with live in the soil, in compost, in rotting fruit. If you were to go into your backyard, if you have a moist area, it’s teaming with nematodes. And we could actually take some of your compost and put it on a plate in our lab and get those nematodes out of it. I’m interested in how these bacteria that they eat can turn into their microbiome because they’re not destroying every single one of the bacterium that they’re eating. And they can potentially change metabolism. And the gut sends signals from the gut to the brain and alter like the life state of the worm.

Brittany Fair
So these nematodes are eating a bacteria, which then can change everything about that nematode?

Molly Matty
Probably. Yeah. So something that’s really cool. It’s like we hear about the microbiome a lot or the microbiota and, uh, we think of it in our gut, maybe on our skin, but like literally every surface has a microbiome. So these nematodes in the lab, we’ve historically only ever fed them the single bacterial species, an e coli. So what I’m doing is I’m giving them this complex mixture of microbes. So now they’re getting a lot more varied, um, nutrients and metabolites from these living bacteria that are inside them.

Brittany Fair
And so once the bacteria is inside them and kind of a part of the nematode, how does it then affect things like metabolism or a signaling to the brain?

Molly Matty
So the gut is in communication with the rest of the body. Um, it’s kind of how we get hangry. Uh, you can think about having a starvation signal from your gut being like, “go get food”! And I’m working on a project right now that actually is focusing on trying to figure out what signaling peptides these little tiny proteins are being sent from a starved worm to the brain of the worm to tell it to change its behavior.

Brittany Fair
Okay.

Molly Matty
And what’s interesting is they partake in what we call a risky behavior.

So they’re more likely to cross a barrier that’s dangerous to them if they’re starved than if they are well fed and they’ll cross that barrier to get to an odor that they think is food. And so this is something that’s already known even between two different strains of the same species of bacteria. So two different e coli, the worms will behave differently.

Brittany Fair
Oh wow. That’s so fascinating.

Molly Matty
And so we, we as a scientific community have a lot of instances where, um, microbes affect behavior. So some are very, uh, dramatic where, um, toxoplasma infections in mice make them less afraid of cats so that the toxoplasma parasite can get into cats, which are their primary vector, right. Rabies virus makes animals afraid of water.

Brittany Fair
Oh, interesting.

Molly Matty
Yeah. Yeah. And uh, one of my favorite examples of this that I shared with a high school student who worked with me this summer, uh, that there’s a virus that infects crickets that makes them more sexually promiscuous and it’s a sexually transmitted virus.
So of course, like that’s really beneficial for this virus to increase copulatory behaviors if that’s how they get around.

Brittany Fair
Wow. Yeah. Okay. So now I’m starting to understand, so you are really looking at the microbes, what the direct effect is internally in order to see how that affects behavior.

Molly Matty
Exactly. Yeah. Yeah. And so I can say with these microbes, how are you behaving differently?

Brittany Fair
Sure. Yeah. And does gut bacteria affect behavior in humans at all?

Molly Matty
There are some studies wherein humans, uh, are given probiotics. So like a yogurt, like, um, material and then given a survey of how they feel. And, um, in those studies they have shown that probiotics like a lactobacillus will improve, uh, depressive like behaviors or anxiety, like behaviors. So, or feelings I guess. So on a, on a survey they would say, I feel less anxious or I feel less depressed than I did before.

Um, but those studies of course are very, Hmm, they’re difficult to control, right? Yeah. So all human studies are difficult to control because we have different genetics, we’ve had different environments and self-reporting is really difficult. But in the worms they are hermaphrodites the ones we keep in the lab or typically hermaphrodites so, okay. They just make copies of themselves.

Brittany Fair
So that makes it easy.

Molly Matty
Yeah. So their genetics is very well controlled. Yeah. So I’ve got a plate of clones and in the plate I can control their environment completely and have, you know, thousands of animals that have had the exact same experience, have nearly the exact same genetics, and then say with this bacterium, are you behaving differently?

Brittany Fair
Okay. Yeah. Yeah. It’s a very elegant model.

Molly Matty
Yeah, exactly. And that’s why it’s called C elegans cause they’re elegant.

Brittany Fair
So before you came to Salk, were you also studying nematodes? microbiota? behavior?

Molly Matty
No, not at all.

Brittany Fair
Oh, okay.

Molly Matty
Yeah, I’m pretty new to everything about my postdoctoral experience. Um, my PhD I did at Duke University and I used zebra fish as a model system to study, um, infections, but a specific type of infection, uh, called mycobacteria. It’s the same bacteria that causes tuberculosis in people. It causes a tuberculosis in fish.

Brittany Fair
Interesting.

Molly Matty
Yeah. Yeah. So we use the same kind of conserved host pathogen interaction in fish with their mycobacteria, their tuberculosis, and use that to understand how humans get tuberculosis and how to treat it better.

Brittany Fair
Interesting.

And that was for your graduate work. So then what really brought you to Salk? Why did you want to come move across the country and start studying tiny worms?

Molly Matty
So I knew I wanted to move into a simpler model and I hate the way that, um, fly food smells. So I decided I wanted to work on worms. Who’s working on C elegans? Sreekanth Chalasani.

and, um, you know, I started reading about what his lab does and like it sounds cool, but it sounds super computational. Like neurocircuits sounds terrifying. I’m not computationally trained. Big data is overwhelming to me.

Brittany Fair
Yeah. It’s intimidating.

Molly Matty
Super intimidating! I don’t have these skills. I’ve never programmed in MATLAB. Um, and in reading, but then in reading some of Shrek’s papers, Shrek’s lab’s, papers, I, I realize the questions that they were asking were intrinsic basic biology questions of as an animal ages, how does it behave? How does its behavior change? Or based on a prior experience, how does an animal’s behavior change? You know, can we teach an animal to avoid scenarios that are good for it if we associate it with a bad thing and what is happening on a neuronal level in those scenarios. And I was like, this is so cool.

Brittany Fair
Oh yes.
And now that you’re here and integrated into the Salk community and you’re involved with Salk’s Education Outreach program.

Molly Matty
Yeah. Yeah. So, um, education outreach at Salk is great when you break it down into these fun analogies. And these, these vignettes of, of the findings for people to understand is when I get really inspired to go back in and do that work. Even if it’s, you know, a long night, it’s really inspiring to talk about my research and other people’s research in a way that, that is compelling to young people and the general public.

Brittany Fair
And when you, uh, volunteer for the program, are you working with middle schoolers or high schoolers? Are they coming to you? Do you go into the classroom? How does it work?

Molly Matty
I’m going to say it’s all of the above. I actually, when I first started, we put together a project where there’s the, this chemical called PTC phenylthiocarbamide that based on your genetics you can either taste it and it tastes bitter and terrible or it doesn’t taste like anything.

Yeah. So, um, it turns out that this PTC taste effect is like a single gene and we know the mutations. You get the kids and their families and anybody to taste this strip of paper with this chemical on it and tell you if they can taste it or not. And then you take them through essentially the central dogma, which is that a gene turns into RNA, turns into a protein. And so we give them their gene sequence, they transcribe it into RNA, and then they turn that RNA into individual amino acids and they wear a little bracelet with their amino acids that are different between the tasters and the non-tasters. We can have them show their bracelets and say, okay, looking at the sequence, do you think you’re a taster or a non-taster? Like, let’s compare. And so they’re essentially doing bioinformatics, right?

Like comparing sequences and putting it into a phenotype. Uh, so I think it’s, I think it’s a really cool activity for kids and adults alike where you can turn something physical that you can see or taste in this, in this case, into the, the gene and into the protein. And it’s really just like this receptor that has a mutated shape and so it can’t catch the flavor.

Brittany Fair
That’s great. And then we actually recently met at a meet and greet for Salk’s Ambassador program. Um, can you tell me about the program and how you’re involved?

Molly Matty
Yeah, so the Salk Ambassadors program is run by the Society of Research Fellows, which is kind of like a postdoc/graduate student association sort of thing here at Salk. And we put together a lot of opportunities for career development, training, and just community building at Salk focused on trainees. Um, so graduate students and postdocs primarily.

The SRF ambassadors program is for incoming trainees who maybe this is their first time in California, maybe their first time in the United States, or maybe just their first time working at the Salk and we match them with somebody with similar interests or background in some way to help them be introduced to the Salk to say, you know, I’m a friendly face. Let me show you around to things like, Oh, you’re a vegan, here are some really good vegan restaurants in San Diego. Yeah. So it’s really just to make Salk a more welcoming place for new incoming people.

Brittany Fair
Well, I think it’s so great that we have this program because so many people who are at Salk are international or not from San Diego. Right?

Molly Matty
Yeah. This is my first time in Southern California at all. And it is very different than the East coast. Like just culturally, you know, uh, the Society of Research Fellows is actually another way that I said. Okay. Salk is big. San Diego is big. I need a community.

Brittany Fair
Sure.

Do you have any hobbies outside of science?

Molly Matty
Outside of science and then telling everybody that I meet about science, I do this thing called, um, called “Uber outreach” where every time I take an Uber or a Lyft, I, uh, try to talk to my driver about science in some way.

Brittany Fair
Okay, wait, so give me an example.

Molly Matty
So, so, um, recently I told somebody that I worked on worms. And they were like, what do you mean, worms? I was like, well, they are microscopic worms.

Brittany Fair
Which is weirder in some ways.

Molly Matty
Exactly. Yeah. It is weird. Yeah. And so then I told him, you know, you know, these worms live in soil like earthworms, but they’re much smaller. And he, uh, wondered why we studied worms. And so similar to like, the first question here was like, why study worms? Like why not use a mouse or you know, something I’ve heard of that kind of resembles a person. So just telling people like, worms have muscles so muscles can atrophy in a worm. So if you’re interested in, you know, any sort of muscular disorder, you can use a worm to study that. The worms even have neurons, like that’s shocking to most people in the public. So just little things like that, um, are kind of my, my Uber outreach endeavors.

But outside of Uber outreach and normal outreach outside of science, what do I like to do? I run. Mmm. I really love running. It’s how I get to know any space that I’m in. So whenever I travel, I go for a long run and, you know, scope out good restaurants or cute little, um, walking areas for later on in the, in the day. But I try to do at least one half marathon a year and try to run my age in like kilometers every year. On my birthday. Okay. Yeah. So, so running is definitely a thing. I call them like Molly marathons. So, um, it started when I was 25 I didn’t start running until I started grad school. And it was a way to de-stress. I decided on my 25th birthday I was going to run a 25K and I was living in Durham, North Carolina.
So I just plotted out what 25 kilometers would be on a nice day in September when my birthday is, what I did was plotted out like a little map and then I get my friends to join me for legs of it. So like they’re kind of doing a relay and then I’m doing the whole thing. Um, yeah. And then the end, we always get ice cream because that’s, that’s why we run is to eat ice cream.

Brittany Fair
And you’re obviously a very successful scientist, but if you woke up tomorrow and someone told you “you cannot be a scientist”, what would be your backup career?

Molly Matty
Uh, so I think about this a lot actually. What I would probably do is be in like marketing, um, because I love puns and jingles and I’m so, I’m so much love, like, yeah, I think I would be really good at marketing everything.

Brittany Fair
So not to put you on the spot and feel free to take some time with this, but do you have any favorite jingles or puns that come to you?

Molly Matty
So I actually, in grad school I entered in pun competitions.

Brittany Fair
I didn’t know that existed or it was a thing.

Molly Matty
Yeah. So, um, so yeah, there, there were these things that you get a topic and you’re made to make puns about them in front of an audience of people. And…

Brittany Fair
Ookay. I’m rephrasing my question.

Okay. Can I just give you like a word?

Molly Matty
Sure. Yeah.

Brittany Fair
Okay. Butterflies.

Molly Matty
Okay. Butterflies. All right. Um, yeah, so butterflies are typically thought of as leaders in the insect community because there’s a lot of monarchs.

Brittany Fair
That was really good. So impressed.

Molly Matty
Yeah. So things like that. Yeah. Or, um, you know, the, the pun competition. Sometimes they give you the setup. Like I went to a movie about butterflies that was so bad and it’s like, how bad was it? Oh, I just, wanted to curl up in a cocoon and die or something. Uh, I felt like, yeah. Yeah. So those types of things. I love comedy. Um, when I was, when I was in middle school, my, my dream career was to be like Weird Al, um, to write like parody songs cause I just, I love seeing like little connections and, and making fun of things and making fun out of things.

Uh, and so I think science is also kind of related to that. And you see connections in a lot of things. And if you’re not having fun, like don’t do it. Like everyday I go to lab and I have a wonderful time. You know, I talk to my friends, I do cool things. I find out something that works or doesn’t work, and um, you know, connect it to something else that I know or don’t know and keep moving forward. So it’s kind of like being a comedian, but, uh, your audience worms.

Brittany Fair
Speaking of which, can I give you one last word? Nematode.

Molly Matty
Mmm. It’s really hard to run, uh, with out appendages. I really need ma toes to run.

Brittany Fair
Haha. That was amazing. Thank you so much Dr. Matty for being on the podcast today. We really enjoyed having you.

Molly Matty
I had a wonderful time.

Announcer:
Join us next time for more cutting edge Salk science. At Salk, world renowned scientists work together to explore big, bold ideas from cancer to Alzheimer’s, aging to climate change. Where Cures Begin is a production of the Salk Institute’s Office of Communications. To learn more about the research discussed today, visit salk.edu/podcast.