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The Fungus You Should Actually Be Worried About

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0:00In the not-too-distant future, a  fungus called Cordyceps will mutate
0:03in response to a warming planet, and  evolve the ability to infect humans.
0:08The fungus takes over its victims’  brains, turning them into zombies,
0:12hellbent on consuming every  living person they can find.
0:15The resulting panic will create a dystopian world
0:18where our survival is far from guaranteed.
0:21Sounds... bad. Lucky for you, that’s  just the plot of The Last of Us,
0:25and not a prediction of the actual future.
0:27As far as we know, anyway.
0:28But if you played the game or  watched the show and have been
0:31worried about Cordyceps becoming a  reality, I do have some bad news for you,
0:36also some good news, and  then some really bad news.
0:39The bad news is that the Cordyceps fungus is real,
0:42and does cause zombie epidemics.
0:44The good news is that it mainly targets  insects and spiders, not humans.
0:49So you don't have to worry about it...for now.
0:51But the really bad news is that there are  plenty of other fungi out there that have
0:55the potential to become a disaster for  us, and fungal infections are on the rise.
1:01Which is why researchers like  Asiya Gusa are so important.
1:05Her work to understand how fungi  adapt to changing environments,
1:08and what they could mean for our health,
1:11can help us prepare for whatever they throw at us.
1:14We sent our friend Madelyn Leembruggen  to Duke University to tour Gusa’s lab
1:18and get a firsthand look at the potential threat.
1:21Get ready for another SciShow Field Trip!
1:24[♪ INTRO]
1:28Thanks, Hank! He’s such a fun-guy.
1:30Stop me if you’ve heard this one before.
1:32One day, totally out of the  blue, a new pathogen evolves from
1:36something more benign, and this new  bug is very good at making us sick.
1:41It’s highly contagious, we don’t have  great medicines or vaccines for it,
1:45and the sudden surge of sick people  throws the entire world into chaos.
1:48If you’re having flashbacks to  sanitizing our groceries in 2020,
1:52well, I don’t blame you.
1:54But when we talk about pandemics, we  tend to think of viruses or bacteria,
1:58things like the flu or COVID or tuberculosis.
2:01What we usually don’t think of are fungi.
2:04Fortunately, Asiya Gusa does.
2:07Gusa is an Assistant Professor of  Molecular Genetics and Microbiology
2:10at Duke University, where she  spends her days studying fungi
2:14that have the potential to  cause dangerous infections.
2:17So as you can imagine, she  talks a lot about fungus.
2:20I noticed that you said fungi. I say fungi.
2:25Fungi, fungi, fungi, however you  want to say it is actually okay.
2:28Okay. Is there like debate in the  community about everyone talking
2:33about whether or not you  want to use a hard g or not?
2:36I've landed on fungi, but  whatever makes you comfortable.
2:38One of your body's great defenses against fungi
2:41is the fact that you are, well, kind of hot.
2:44And I mean that literally.
2:46So why are fungal infections  not very common in humans?
2:49It's a really good question, and we  think that it's actually a lot of it
2:52has to do with our higher body temperature.
2:54So our higher body temperature serves  as a natural kind of thermal barrier.
2:58Since most environmental fungi that  we breathe in in the environment,
3:02they actually can't grow that  well at our body temperature.
3:05They prefer cooler temperatures,  like around 25 to 30 degrees Celsius,
3:09because they live in the soils  and they live on plant matter.
3:12So we actually have sort of  a natural defense mechanism
3:16of our higher body temperature.
3:17But there’s a group of fungi that  have the potential to change that,
3:21which is why Gusa and her team are studying them.
3:23They’re called Cryptococcus.
3:25These fungi are already known  to cause serious infections
3:28in some immunocompromised people.
3:30That’s because, even though our  body heat holds most fungi at bay,
3:34our immune systems still have to finish them off.
3:36And as the planet warms, Cryptococcus  might be adapting to survive better and for
3:41longer at the higher temperatures that  usually keep them out of all of our bodies.
3:45So actually, in the laboratory,  we study a species of Cryptococcus
3:49that's less thermal tolerant, so it  can't survive well at body temperature.
3:54And so those are the ones we're most  interested in studying and figuring out if,
3:57if they cross that temperature threshold,
4:00they are possibly going to cause  a greater number of disease,
4:04increase in incidents, and  also severity of disease.
4:08Organisms are constantly adapting  to the world around them,
4:11and some of them, like Cryptococcus,  are very good at doing that.
4:16Like all living things, these  fungi are always mutating,
4:19sometimes based on random changes  to single base pairs in their DNA.
4:23These little changes can add up over time,
4:25creating big alterations in  how the organism functions.
4:29What we're in right now is  a big 30 degree incubator.
4:32So think of like a walk in fridge.
4:34Like a cold room, for example.
4:36Same thing, but the opposite.
4:37That’s Cheyenne Lee, a  postdoc working in Gusa’s lab.
4:40The reason that we have this here,  basically is the cryptococcus cells
4:44that we grow primarily grow at 30 degrees Celsius.
4:48So in this room, they're not feeling the stress.
4:50Yeah, they’re not feeling  that heat temperature stress.
4:52So these are just some little  crypto cells on the plate.
4:56And then I have another one that  was previously grown at 37 degrees.
5:00So you'll notice that
5:01There's fewer of them
5:02There's a lot smaller colonies on the plate,
5:04because they were very stressed  out at that higher temperature.
5:08I also get stressed when it’s too hot.
5:10Me too!
5:10In addition to getting stressed in the heat,
5:13something interesting changes  about the way Cryptococcus mutates.
5:16Gusa found that the mutation rate  is connected to the temperature
5:20around the fungus while it’s growing.
5:22When Cryptococcus was grown at 37 degrees Celsius,
5:25it mutated five times faster  compared to when it was grown
5:30at its more typical 30 degrees Celsius.
5:32But what Gusa found even more  interesting about her studies was
5:36how Cryptococcus was mutating.
5:38These weren't just single base pair  changes that were accumulating.
5:42There were these big chunks of DNA  actually jumping around, called,
5:45well, jumping genes, or transposable elements.
5:49These transposable elements can have a  big impact on how genes are expressed.
5:54I even got a hands-on look at how  they study these jumping genes!
5:57What I'm going to actually show you  guys today is how do we check to see,
6:03has that jumping gene actually jumped?
6:05You know? So that's what I'm  going to be looking at here.
6:08We're going to see how the jumping gene, jumps.
6:10Yes.
6:11We’re about to do a test  called gel electrophoresis.
6:13The researchers isolate a  segment of DNA, chop it up,
6:16and stick it on a gel plate, which  they run an electric current through.
6:20This causes the DNA to sort itself by size,
6:23and those bigger pieces are  where the jumping genes landed.
6:26So if you want, do you remember how  I loaded that at the very beginning?
6:30You've been watching this.
6:31Yeah yeah.
6:32Do you feel brave?
6:34I can be brave.
6:35All right, so what I'm gonna  have you do is load one of those.
6:37We have to be very gentle and load slow. Gentle, very go slow, okay.
6:37So that's it. But you got it. You'll be fine.
6:37You can live that right next  to where I just put mine.
6:38Okay, yeah. So here's that first stop,  okay, there you go, wonderful, okay,
6:41and then right next to her, yes,  or wherever you want, really,
6:45wherever you're comfortable. I'll work around it. That's perfect, beautiful.
6:48So many times, did you see  it taller than the line?
6:48Yeah, a little left in there.
6:48That's okay, oh, like, get it  towards the end, and there you go.
6:51Now press the rest of it.
6:53There you go. Perfect. All right, that  should be enough. You got it. You got it.
6:57So now the next button that  you can press is right there.
7:00Press on it. Yay! Great job, you did it!
7:03Thank you for teaching me to pipette!
7:04Combined with the rapid rate of mutation,  these jumping genes can lead to the
7:08kind of heat tolerance that some species  of Cryptococcus have shown lately.
7:12As if that’s not bad enough, Gusa  found that this higher mutation rate
7:16can give Cryptococcus a really  nasty superpower: Drug resistance.
7:21So these are the drug resistant colonies,  basically on both of these plates
7:2537 degrees these were the  ones that were stressed out.
7:27You can see, just like on the  other plates, they were a lot less.
7:30And what we're looking at are  spontaneous, drug resistant mutants.
7:35So if you grow up a population of  cells, a small percentage of them
7:39will have a mutation that will allow  them to grow on a drug containing plate.
7:43And so this is kind of a proxy for us  to figure out if there's been a mutation
7:48that has caused this  particular phenotype to arise,
7:51which is drug resistance in this case.
7:53So then we can actually go in,  extract the DNA and find out what
7:57that genetic change has occurred.
7:59And in some cases, we find transposable elements
8:02have inserted into our gene  causing the drug resistance.
8:05Even the drugs that currently exist  for Cryptococcus aren’t great.
8:08The ideal treatment involves  multiple antifungal drugs,
8:12which are often toxic and  difficult for people to handle.
8:15Gusa told us that one of the  biggest challenges in treating these
8:18more serious fungal infections  is that there just hasn't been
8:21a lot of research done to  improve these antifungal drugs.
8:25And so what we really need are  better drugs to treat fungal diseases
8:29and just to be prepared in  case we need fungal vaccines.
8:32Right now, there are no fungal  vaccines to treat humans,
8:35and so that's a big concern.
8:36And then a lot of the drugs that we have to
8:38treat fungal infections were very antiquated.
8:40They were developed a long time ago.
8:42They actually have a lot of toxic side effects,
8:45so more investment is needed in  developing effective drugs and drugs
8:48that people can take, potentially orally, to  treat fungal infections that are invasive.
8:52That’s another potential  benefit of Gusa’s research.
8:55If she can identify the conditions and  substances that kill certain fungi,
9:00it could lead to promising antifungal treatments.
9:03For example, the fungus that  makes penicillin, Pennicillium,
9:06makes its own antibiotics to reduce resource
9:09competition in its environment  by killing nearby bacteria.
9:12Why is it so important to keep  exploring and to keep finding new fungi?
9:16Well, again, as I'm learning,  fungi are amazing natural resources
9:21that have been underutilized, and so  just like with the study of bacteria,
9:26which people know a lot more about, with fungi,
9:28they also can produce all these amazing compounds.
9:31There's undiscovered potential for  them in a lot of different realms.
9:34So fungi have a long history of being  exploited for their ability to treat
9:41not only other fungi, to kill  other fungi, but to kill bacteria.
9:45They're also involved in  statins for like cholesterol,
9:49psilocybin is being studied for  potential antidepressant activity.
9:53There's lots of different uses  for fungi, and for the most part,
9:56we really, we value and we gain a  lot of amazing products from fungi.
10:02And we're actually now starting  to look at ways in which fungi,
10:05since they're natural  decomposers in our environment,
10:07that they may be able to degrade plastics.
10:10So one of my newest students is actually  working on a plastic pollution project
10:13where we're screening fungi for  the ability to break down compounds
10:17that are much more difficult to break down  by the enzymes that we currently have.
10:21And so this is one of the reasons or  resources that sort of an unexpected find
10:25in our science, that we  can actually utilize fungi,
10:29not only to be just afraid of them,
10:32but what can we actually harness the  power of fungi to do in our laboratory?
10:36How many like, if you had to  estimate what percentage of fungi
10:42in the world we've already learned about  what percentage do you think that is?
10:47I think I've seen figures like this, and  they put it like we probably surveyed,
10:51about 3% of what's actually out there.
10:53Yeah, fungi are historically understudied,
10:57and there's so many different varieties,
10:58you can probably go into your background
11:00and your backyard and actually  find a new fungal species.
11:02Gusa’s team has started to close this  gap, and it began in an unusual way.
11:07In September of 2024,  Hurricane Helene swept across
11:11the southeastern part of the US  and was particularly devastating to
11:15Southern Appalachia, killing at  least 250 people and leading to
11:19flooding that caused immense damage.
11:21In the aftermath, Gusa and  her team visited the areas
11:24that had been flooded with one  specific goal: to collect fungi.
11:29And so these were isolated after Hurricane Helene,
11:32we went and did environmental sampling,
11:34and we've been able to curate this  amazing resource that can now be used
11:38for potentially natural product  discovery and also to understand
11:42what kinds of mycotoxins or harmful allergens
11:46they might be producing that  might be making people sick.
11:49Gusa’s lab collected hundreds of  fungal samples from Black Mountain,
11:52North Carolina, an area that was hit  especially hard by Hurricane Helene.
11:57The team has catalogued all sorts of  important information like the species,
12:01origins, and genetic sequence  to create a fungal biobank.
12:05We have quite a variety we wanted to show you
12:08of just different phenotypes  on the different plates.
12:10We talked with Sam Shaltz and  Gabrielle Walker to learn more.
12:13But basically what happened  is we got a swab of all these
12:16different environmental samples,
12:17and my job is to go through and try  to isolate out different species.
12:22And then once they're isolated out,
12:23this is a good example of them being  isolated on different types of plates.
12:27I then go through and I have to identify them.  
12:30So you've, you're basically starting  this, like big library of fungi.
12:36Yeah, yeah. And we have, again, we  have a lot of species right now.
12:40I think we have about 65 in our biobank.
12:42At the moment, all of them have  been isolated and identified,
12:4741 unique species, and out of them,
12:49about 10 of them are potential fungal pathogens.
12:52What kinds of things are you looking for from
12:54the biobank as you assemble all these samples?
12:57So we're trying to just basically  find out the fungal abundance.
13:01The neat thing is that we can  track which sample we have here,
13:06where the swab came from.
13:07And then the one neat thing  too, is with our fungal biobank,
13:11we also are recording the pictures as well.
13:14So this will be also very useful for  people in the future to reference
13:18making sure that when they do use our samples,
13:20they can look at our pictures  and make sure that what
13:23they're growing looks like  what we have growing here.
13:26In addition to investigating which  fungi might lead to infections,
13:29Gusa’s lab will use the  biobank to conduct research
13:32on potentially dangerous  chemicals that fungi can make.
13:35We have other researchers at Duke.
13:37There are my collaborators  that are going to be looking
13:39at what kind of toxins do fungi produce  as they're consuming different materials.
13:44So when they're growing on things like  drywall or on the surfaces of plastics,
13:48what are they actually  producing as they metabolize?
13:51And so some of the things that they secrete  into the air, in addition to spores,
13:56are things known as mycotoxins and  also volatile organic compounds.
14:01You know that musty, earthy  smell in a damp basement?
14:05That’s partly made up of  VOCs, cooked up by fungus.
14:08The effect of VOCs on our health is less clear,
14:12which is why Gusa wants to study them.
14:14So this is sort of a whole new area of  research that has been under studied again,
14:18and we really don't have an idea about  what kind of health impacts result,
14:22but we certainly know that we  already know of certain allergens
14:25that are caused by some of these fungi  that are growing from indoor mold sources.
14:29But we want to learn more  about mycotoxins and VOCs.
14:32Having this biobank might even help us identify
14:34some of those fungus-fighting-fungi  we were talking about before.
14:38Or, we may even find fungi  that can help us in other ways.
14:42So this is the one of the fungal  species that I'm working with right now
14:46to identify to be able to degrade plastic.
14:50And so from what I found, from  some of our preliminary results
14:54is that this species can degrade a polyester  polyurethane polymer called Inferno,
15:01and it's doing really amazing.
15:02So what some of my next steps  are is identifying what enzymes
15:07are being secreted by Aspergillus that  can degrade that particular polymer.
15:12And we think that this is  a possibility that we can
15:14go from natural disaster to natural  discovery, and that's really exciting
15:17I have to admit that when our lab first started,
15:20it was kind of all about the doom and gloom,
15:22oh, the threat of fungi and like,  you know, disease and you know,
15:25which is very serious, and  we really do care about it,
15:27but it was nice to have another  side where we can also talk about
15:31the solutions that fungi might be able to provide.
15:33And so that's been really exciting,  and a nice balance in the lab.
15:37All this is especially cool because  the Gusa lab is still pretty new,
15:41and they’re only just getting started.
15:43Gusa had a different path to becoming  a research scientist than most.
15:47After earning her PhD, she spent a fair bit  of time as a high school science teacher.
15:51I got to be able to learn how to  communicate science and really inspire,
15:54hopefully, the next, future  generation of scientists.
15:57And so I had this really incredible  opportunity to come back a little bit
16:00later in life to be a  researcher at Duke University,
16:03which has been one of my dreams.
16:05And so now, instead of, you  know, teaching in the classroom,
16:07I have a classroom in the laboratory,
16:09and I'm able to really  mentor my students and, like,
16:12really see them grow and  thrive in their own right.
16:15So it's been really exciting transition for me.
16:17And as it turns out, when we got here  we realized she’s already a SciShow fan.
16:21Did you ever use SciShow videos?
16:25I sure did. Yeah. Hank Green, you  were a constant in my classroom.
16:29Yeah. So just the way that  SciShow broke things down,
16:33it was able to really just  augment the lectures I had in
16:35a fun and very relatable way with our students.
16:38So I know when I told my lab that, you  know, SciShow was coming to our lab,
16:41they were super excited.
16:42They're like, what are you serious?
16:44I can't wait to be a part of this.
16:46So yeah, we're really excited that you  guys were able to come and visit with us.
16:49We're so excited you guys joined our ecosystem,
16:52and now you and your research  get to go be in other classrooms.
16:56It's full circle.
16:58Yeah absolutely.
16:59The work that Gusa and her lab are  doing is vital for helping us understand
17:03why and how fungi can be so dangerous to us,
17:06and even let us develop new medicines, too.
17:09All of which could be very  useful… whether we’re facing down
17:13just a bit of mold overgrowth, or  a full-on fungal zombie apocalypse.
17:18SciShow Field Trips are made with our  friends at HHMI Tangled Bank Studios.
17:22We’ve come together to bring you  face to face with researchers
17:25at the cutting edge of scientific discovery.
17:27You can watch more of Tangled Bank’s  science content at tangledbankstudios.org.
17:32[♪ OUTRO]