In the not-too-distant future, a  fungus called Cordyceps will mutate in response to a warming planet, and  evolve the ability to infect humans.

The fungus takes over its victims’  brains, turning them into zombies, hellbent on consuming every  living person they can find. The resulting panic will create a dystopian world where our survival is far from guaranteed.

Sounds... bad. Lucky for you, that’s  just the plot of The Last of Us, and not a prediction of the actual future. As far as we know, anyway.

But if you played the game or  watched the show and have been worried about Cordyceps becoming a  reality, I do have some bad news for you, also some good news, and  then some really bad news. The bad news is that the Cordyceps fungus is real, and does cause zombie epidemics. The good news is that it mainly targets  insects and spiders, not humans.

So you don't have to worry about it...for now. But the really bad news is that there are  plenty of other fungi out there that have the potential to become a disaster for  us, and fungal infections are on the rise. Which is why researchers like  Asiya Gusa are so important.

Her work to understand how fungi  adapt to changing environments, and what they could mean for our health, can help us prepare for whatever they throw at us. We sent our friend Madelyn Leembruggen  to Duke University to tour Gusa’s lab and get a firsthand look at the potential threat. Get ready for another SciShow Field Trip! [♪ INTRO] Thanks, Hank!

He’s such a fun-guy. Stop me if you’ve heard this one before. One day, totally out of the  blue, a new pathogen evolves from something more benign, and this new  bug is very good at making us sick.

It’s highly contagious, we don’t have  great medicines or vaccines for it, and the sudden surge of sick people  throws the entire world into chaos. If you’re having flashbacks to  sanitizing our groceries in 2020, well, I don’t blame you. But when we talk about pandemics, we  tend to think of viruses or bacteria, things like the flu or COVID or tuberculosis.

What we usually don’t think of are fungi. Fortunately, Asiya Gusa does. Gusa is an Assistant Professor of  Molecular Genetics and Microbiology at Duke University, where she  spends her days studying fungi that have the potential to  cause dangerous infections.

So as you can imagine, she  talks a lot about fungus. I noticed that you said fungi. I say fungi.

Fungi, fungi, fungi, however you  want to say it is actually okay. Okay. Is there like debate in the  community about everyone talking about whether or not you  want to use a hard g or not?

I've landed on fungi, but  whatever makes you comfortable. One of your body's great defenses against fungi is the fact that you are, well, kind of hot. And I mean that literally.

So why are fungal infections  not very common in humans? It's a really good question, and we  think that it's actually a lot of it has to do with our higher body temperature. So our higher body temperature serves  as a natural kind of thermal barrier.

Since most environmental fungi that  we breathe in in the environment, they actually can't grow that  well at our body temperature. They prefer cooler temperatures,  like around 25 to 30 degrees Celsius, because they live in the soils  and they live on plant matter. So we actually have sort of  a natural defense mechanism of our higher body temperature.

But there’s a group of fungi that  have the potential to change that, which is why Gusa and her team are studying them. They’re called Cryptococcus. These fungi are already known  to cause serious infections in some immunocompromised people.

That’s because, even though our  body heat holds most fungi at bay, our immune systems still have to finish them off. And as the planet warms, Cryptococcus  might be adapting to survive better and for longer at the higher temperatures that  usually keep them out of all of our bodies. So actually, in the laboratory,  we study a species of Cryptococcus that's less thermal tolerant, so it  can't survive well at body temperature.

And so those are the ones we're most  interested in studying and figuring out if, if they cross that temperature threshold, they are possibly going to cause  a greater number of disease, increase in incidents, and  also severity of disease. Organisms are constantly adapting  to the world around them, and some of them, like Cryptococcus,  are very good at doing that. Like all living things, these  fungi are always mutating, sometimes based on random changes  to single base pairs in their DNA.

These little changes can add up over time, creating big alterations in  how the organism functions. What we're in right now is  a big 30 degree incubator. So think of like a walk in fridge.

Like a cold room, for example. Same thing, but the opposite. That’s Cheyenne Lee, a  postdoc working in Gusa’s lab.

The reason that we have this here,  basically is the cryptococcus cells that we grow primarily grow at 30 degrees Celsius. So in this room, they're not feeling the stress. Yeah, they’re not feeling  that heat temperature stress.

So these are just some little  crypto cells on the plate. And then I have another one that  was previously grown at 37 degrees. So you'll notice that There's fewer of them There's a lot smaller colonies on the plate, because they were very stressed  out at that higher temperature.

I also get stressed when it’s too hot. Me too! In addition to getting stressed in the heat, something interesting changes  about the way Cryptococcus mutates.

Gusa found that the mutation rate  is connected to the temperature around the fungus while it’s growing. When Cryptococcus was grown at 37 degrees Celsius, it mutated five times faster  compared to when it was grown at its more typical 30 degrees Celsius. But what Gusa found even more  interesting about her studies was how Cryptococcus was mutating.

These weren't just single base pair  changes that were accumulating. There were these big chunks of DNA  actually jumping around, called, well, jumping genes, or transposable elements. These transposable elements can have a  big impact on how genes are expressed.

I even got a hands-on look at how  they study these jumping genes! What I'm going to actually show you  guys today is how do we check to see, has that jumping gene actually jumped? You know?

So that's what I'm  going to be looking at here. We're going to see how the jumping gene, jumps. Yes.

We’re about to do a test  called gel electrophoresis. The researchers isolate a  segment of DNA, chop it up, and stick it on a gel plate, which  they run an electric current through. This causes the DNA to sort itself by size, and those bigger pieces are  where the jumping genes landed.

So if you want, do you remember how  I loaded that at the very beginning? You've been watching this. Yeah, yeah.

Do you feel brave? I can be brave. All right, so what I'm gonna  have you do is load one of those.

We have to be very gentle and load slow. Gentle, very go slow, okay. So that's it.

But you got it. You'll be fine. You can live that right next  to where I just put mine.

Okay, yeah. So here's that first stop,  okay, there you go, wonderful, okay, and then right next to her, yes,  or wherever you want, really, wherever you're comfortable. I'll work around it.

That's perfect, beautiful. So many times, did you see  it taller than the line? Yeah, a little left in there.

That's okay, oh, like, get it  towards the end, and there you go. Now press the rest of it. There you go.

Perfect. All right, that  should be enough. You got it.

You got it. So now the next button that  you can press is right there. Press on it.

Yay! Great job, you did it! Thank you for teaching me to pipette!

Combined with the rapid rate of mutation,  these jumping genes can lead to the kind of heat tolerance that some species  of Cryptococcus have shown lately. As if that’s not bad enough, Gusa  found that this higher mutation rate can give Cryptococcus a really  nasty superpower: Drug resistance. So these are the drug resistant colonies,  basically on both of these plates 37 degrees these were the  ones that were stressed out.

You can see, just like on the  other plates, they were a lot less. And what we're looking at are  spontaneous, drug resistant mutants. So if you grow up a population of  cells, a small percentage of them will have a mutation that will allow  them to grow on a drug containing plate.

And so this is kind of a proxy for us  to figure out if there's been a mutation that has caused this  particular phenotype to arise, which is drug resistance in this case. So then we can actually go in,  extract the DNA and find out what that genetic change has occurred. And in some cases, we find transposable elements have inserted into our gene  causing the drug resistance.

Even the drugs that currently exist  for Cryptococcus aren’t great. The ideal treatment involves  multiple antifungal drugs, which are often toxic and  difficult for people to handle. Gusa told us that one of the  biggest challenges in treating these more serious fungal infections  is that there just hasn't been a lot of research done to  improve these antifungal drugs.

And so what we really need are  better drugs to treat fungal diseases and just to be prepared in  case we need fungal vaccines. Right now, there are no fungal  vaccines to treat humans, and so that's a big concern. And then a lot of the drugs that we have to treat fungal infections were very antiquated.

They were developed a long time ago. They actually have a lot of toxic side effects, so more investment is needed in  developing effective drugs and drugs that people can take, potentially orally, to  treat fungal infections that are invasive. That’s another potential  benefit of Gusa’s research.

If she can identify the conditions and  substances that kill certain fungi, it could lead to promising antifungal treatments. For example, the fungus that  makes penicillin, Pennicillium, makes its own antibiotics to reduce resource competition in its environment  by killing nearby bacteria. Why is it so important to keep  exploring and to keep finding new fungi?

Well, again, as I'm learning,  fungi are amazing natural resources that have been underutilized, and so  just like with the study of bacteria, which people know a lot more about, with fungi, they also can produce all these amazing compounds. There's undiscovered potential for  them in a lot of different realms. So fungi have a long history of being  exploited for their ability to treat not only other fungi, to kill  other fungi, but to kill bacteria.

They're also involved in  statins for like cholesterol, psilocybin is being studied for  potential antidepressant activity. There's lots of different uses  for fungi, and for the most part, we really, we value and we gain a  lot of amazing products from fungi. And we're actually now starting  to look at ways in which fungi, since they're natural  decomposers in our environment, that they may be able to degrade plastics.

So one of my newest students is actually  working on a plastic pollution project where we're screening fungi for  the ability to break down compounds that are much more difficult to break down  by the enzymes that we currently have. And so this is one of the reasons or  resources that sort of an unexpected find in our science, that we  can actually utilize fungi, not only to be just afraid of them, but what can we actually harness the  power of fungi to do in our laboratory? How many like, if you had to  estimate what percentage of fungi in the world we've already learned about  what percentage do you think that is?

I think I've seen figures like this, and  they put it like we probably surveyed, about 3% of what's actually out there. Yeah, fungi are historically understudied, and there's so many different varieties, you can probably go into your background and your backyard and actually  find a new fungal species. Gusa’s team has started to close this  gap, and it began in an unusual way.

In September of 2024,  Hurricane Helene swept across the southeastern part of the US  and was particularly devastating to Southern Appalachia, killing at  least 250 people and leading to flooding that caused immense damage. In the aftermath, Gusa and  her team visited the areas that had been flooded with one  specific goal: to collect fungi. And so these were isolated after Hurricane Helene, we went and did environmental sampling, and we've been able to curate this  amazing resource that can now be used for potentially natural product  discovery and also to understand what kinds of mycotoxins or harmful allergens they might be producing that  might be making people sick.

Gusa’s lab collected hundreds of  fungal samples from Black Mountain, North Carolina, an area that was hit  especially hard by Hurricane Helene. The team has catalogued all sorts of  important information like the species, origins, and genetic sequence  to create a fungal biobank. We have quite a variety we wanted to show you of just different phenotypes  on the different plates.

We talked with Sam Shaltz and  Gabrielle Walker to learn more. But basically what happened  is we got a swab of all these different environmental samples, and my job is to go through and try  to isolate out different species. And then once they're isolated out, this is a good example of them being  isolated on different types of plates.

I then go through and I have to identify them.   So you've, you're basically starting  this, like big library of fungi. Yeah, yeah. And we have, again, we  have a lot of species right now.

I think we have about 65 in our biobank. At the moment, all of them have  been isolated and identified, 41 unique species, and out of them, about 10 of them are potential fungal pathogens. What kinds of things are you looking for from the biobank as you assemble all these samples?

So we're trying to just basically  find out the fungal abundance. The neat thing is that we can  track which sample we have here, where the swab came from. And then the one neat thing  too, is with our fungal biobank, we also are recording the pictures as well.

So this will be also very useful for  people in the future to reference making sure that when they do use our samples, they can look at our pictures  and make sure that what they're growing looks like  what we have growing here. In addition to investigating which  fungi might lead to infections, Gusa’s lab will use the  biobank to conduct research on potentially dangerous  chemicals that fungi can make. We have other researchers at Duke.

There are my collaborators  that are going to be looking at what kind of toxins do fungi produce  as they're consuming different materials. So when they're growing on things like  drywall or on the surfaces of plastics, what are they actually  producing as they metabolize? And so some of the things that they secrete  into the air, in addition to spores, are things known as mycotoxins and  also volatile organic compounds.

You know that musty, earthy  smell in a damp basement? That’s partly made up of  VOCs, cooked up by fungus. The effect of VOCs on our health is less clear, which is why Gusa wants to study them.

So this is sort of a whole new area of  research that has been under studied again, and we really don't have an idea about  what kind of health impacts result, but we certainly know that we  already know of certain allergens that are caused by some of these fungi  that are growing from indoor mold sources. But we want to learn more  about mycotoxins and VOCs. Having this biobank might even help us identify some of those fungus-fighting-fungi  we were talking about before.

Or, we may even find fungi  that can help us in other ways. So this is the one of the fungal  species that I'm working with right now to identify to be able to degrade plastic. And so from what I found, from  some of our preliminary results is that this species can degrade a polyester  polyurethane polymer called Inferno, and it's doing really amazing.

So what some of my next steps  are is identifying what enzymes are being secreted by Aspergillus that  can degrade that particular polymer. And we think that this is  a possibility that we can go from natural disaster to natural  discovery, and that's really exciting I have to admit that when our lab first started, it was kind of all about the doom and gloom, oh, the threat of fungi and like,  you know, disease and you know, which is very serious, and  we really do care about it, but it was nice to have another  side where we can also talk about the solutions that fungi might be able to provide. And so that's been really exciting,  and a nice balance in the lab.

All this is especially cool because  the Gusa lab is still pretty new, and they’re only just getting started. Gusa had a different path to becoming  a research scientist than most. After earning her PhD, she spent a fair bit  of time as a high school science teacher.

I got to be able to learn how to  communicate science and really inspire, hopefully, the next, future  generation of scientists. And so I had this really incredible  opportunity to come back a little bit later in life to be a  researcher at Duke University, which has been one of my dreams. And so now, instead of, you  know, teaching in the classroom, I have a classroom in the laboratory, and I'm able to really  mentor my students and, like, really see them grow and  thrive in their own right.

So it's been really exciting transition for me. And as it turns out, when we got here  we realized she’s already a SciShow fan. Did you ever use SciShow videos?

I sure did. Yeah. Hank Green, you  were a constant in my classroom.

Yeah. So just the way that  SciShow broke things down, it was able to really just  augment the lectures I had in a fun and very relatable way with our students. So I know when I told my lab that, you  know, SciShow was coming to our lab, they were super excited.

They're like, what are you serious? I can't wait to be a part of this. So yeah, we're really excited that you  guys were able to come and visit with us.

We're so excited you guys joined our ecosystem, and now you and your research  get to go be in other classrooms. It's full circle. Yeah, absolutely.

The work that Gusa and her lab are  doing is vital for helping us understand why and how fungi can be so dangerous to us, and even let us develop new medicines, too. All of which could be very  useful… whether we’re facing down just a bit of mold overgrowth, or  a full-on fungal zombie apocalypse. SciShow Field Trips are made with our  friends at HHMI Tangled Bank Studios.

We’ve come together to bring you  face to face with researchers at the cutting edge of scientific discovery. You can watch more of Tangled Bank’s  science content at tangledbankstudios.org. [♪ OUTRO]