February 21, 2025 • 25 mins
The Director of the Milner Centre for Evolution, Professor Turi King, talks to Dr Daniel Henk whose research focuses on the evolution and ecology of fungi.
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(00:02):
Hello and welcome. You are listening to a podcast by the Milner Centre for Evolution
at the University of Bath. I'm Professor Turi King, your host, and today I'm talking
to Daniel Hank, whose research focuses on the evolution and ecology of fungi. Dan,
for those who don't know, what are fungi?Well, fungi are organisms relatively closely
(00:30):
related to animals. Sometimes they're called a kingdom of fungi. And they are difficult
to pin down with, like, a synapomorphy. The ones that we know the best will be mushrooms,
but also yeasts, right. So, yeasts that we use in baking and fermentations of all sorts, beers,
(00:50):
and wines. Those are the fungi that we're most familiar with. But there are fungi everywhere.
So even the mushrooms you think about as the fungus. But in fact, most of the mushroom fungus
is down there in the ground and growing completely out of sight and busy being a microbe for almost,
you know, all of its life, except for this little flash in the pan where it makes a big mushroom.
(01:14):
Other fungi that people run into all the time are in their bathrooms, where it's like this mould
on the walls or in their kitchens where it's mouldy food, or occasionally on the outside of
your cheeses, which is really delicious.So, fungi are all around and you can't
really avoid them, humans interact with fungi all the time. But what they are,
(01:36):
that's a trickier question for me, because there's no thing that we can point to and say, that's
what a fungus is. But in a lot of ways, even though they're more closely related to animals,
and they were studied as plants for a long time, they're more like bacteria in a lot of these ways
when we think about how much diversity there is.So, what's their place in the
ecosystem? What do they do?The main thing about fungi is they
(01:56):
eat outside of themselves, right. So, they secrete enzymes that adjust their surroundings, and then
they absorb the nutrients from that. So, they are functional as decomposers, often. So, they're out
there in the soil mixing it up with bacteria, sort of degrading stuff and eating it that way.
They also form symbiosis, which I think is one of the key ingredients for fungi. So,
(02:19):
they form important symbiosis with plants, mycorrhizae, which many people will have heard
of this wood wide web that gets talked about sometimes where fungi are down in the ground,
connecting trees and plants of different sorts. So, they form a special relationship on the
outside and inside of root tips, and then go out and forage for nutrients that plants can't
(02:40):
get. In exchange they get carbon from plants.Fungi are also in the air you're breathing right
now. So, they're kind of in every environment that you can think of. They're in aquatic systems as
well, especially again, like decomposing but also as parasites. So, for every symbiont out
there that's living in a mutualistic relationship, there's a symbiont out there that's busy taking
(03:03):
advantage of a host and being a parasite.Yeah, fungi do all kinds of things. They
live inside of organisms; they live outside of organisms. They live on their own, they live
up in the space station because you can't get rid of it. They live in Antarctic ice. You can
find fungi from ice cores going back millions of years. So, they're kind of in everything.
(03:25):
So, the more I read about this subject, the more I realize just how extraordinary they are. So,
what was it that got you into studying these?Oh, yeah. Purely a person, not actually the
organism so much at all. So, I managed to get a job working with Meredith Blackwell,
who is a fantastic mycologist, and she started me doing a bit of research on
(03:49):
fungi that live on the outside of termites.So, these are like really tiny. These are like,
you know, a 10th of a millimetre in length. So, they're pretty much invisible unless you get them
under a microscope. But they're part of a group of fungi that's incredibly beautiful. So, they come
in a variety of shapes. They're one of the only groups of fungi that has determinate growth. So,
(04:11):
they don't just go on and on making hyphae, they come like in a predetermined set number
of cells that they're going to make. And they look kind of like tiny, microscopic peacocks
stuck on the outside of insects. Really, really weird, but also really beautiful.
And I was working with her and a postdoc in the lab at the time, Alex Weir, and we were sort of
(04:37):
cataloguing these things and trying to answer questions about them, including finding new
species of them. It turns out there are a lot of new fungal species to discover, but at the time,
I was just so excited. I felt like I was on the frontier of something that was new,
and I was one of like five people in the world that had ever seen this before,
(04:58):
right, it felt so exciting to me.And Meredith is also an extremely charismatic
person and a cheerleader for fungi, and I was sucked into many fungal things because of her,
like the fungi were beautiful, and that was cool, but it was because of her, really, that I did it.
So how did you come to be working on what you're working on now?
(05:20):
So, I was super excited as an undergraduate about fungi. Meredith got me very interested in these
kind of, like, unique things and feeling like I was on the cutting edge of something. And when I
was thinking about going to graduate school, she guided me to Duke, where I was going to work with
my professor, Rytas Vilgalys. He's well-known as a mushroom researcher, at that time that's
(05:43):
most of what his lab was doing. And Meredith and I were talking about what I could possibly
do that would still be, you know, exciting to me because I really like these things that live with
insects. And she pointed me in the direction of this fungus that infects scale insects.
So, I don't know whether you're familiar with scale insects, but these are armoured scale
(06:05):
insects, so they have a pretty depressing life. So, they emerge from an egg, crawl around for a
little while, but then they settle down on the outside of a plant, and then they lose
the ability to crawl or anything, and they're stuck on this little spot on a plant, and they
turn into a giant blob with their mouths down in the plants, feeding on specialized plant cells.
(06:25):
But they're good targets for fungi because they just sit there and they aren't going anywhere,
and fungi can grow in them. And what the fungi that I worked on did was infected scale insects
at that crawler stage and then grew inside of them, but didn't actually kill the insects. So,
they actually kept the insects alive but proliferated inside of the insects. So,
(06:50):
that rather than being a blob of insect, they were a blob of fungus, still alive, still feeding on
the host plant, still doing all their stuff, but never able to reproduce. So, this is bad fitness
for those individual insects that are infected.But with the fungus also does is it grows out of
the individual infected insects and makes a giant mat, kind of like a lichen, over a whole colony
(07:15):
of insects. So, within this mat of fungi, this animal lichen, you'll have some infected insects,
but also a lot of uninfected insects that are then embedded in this protective layer of fungi.
So, this was really exciting to me. And I was like, okay, we're going to work on this as a PhD
project. So, I went with my curiosity to do that, and I was really excited about symbiosis. But by
(07:41):
the time I finished my PhD, I was a little more jaded on just the pure excitement of that science,
because I did so much work on this thing, and I felt like maybe that's not really going anywhere
to make the world a better place. It's really cool and we can find out lots of neat stuff,
and I'm all for that. But I just had a kid, and I was thinking about like,
what am I doing to make this place better for him? And you know, for all of us, and I sort of
(08:07):
shifted gears a bit. And when I moved to the UK, I wanted to work on fungi that actually
infect people or interact more with people.So, I was sort of expanding my horizons from
fungal interactions and weird evolutionary stories to more, fungal interactions that matter to us,
and evolutionary stories and trajectories that affect people's lives. And now I've sort of
(08:32):
continued in that vein. So, I sort of still bring the fungal ecology and evolutionary biology,
but I am very interested in applications with fungi that affect how we live.
So, tell me about these fungi that interact with humans. So,
what were the two that you were looking at and how do they interact? How they affect us?
Okay. So, you're breathing fungi all the time. That is a common feature for both of
(08:58):
these fungi that I was working on. They make ubiquitous spores, they're in the air. And
when you breathe them in normally, a healthy immune system and a healthy person responds,
basically by protecting yourself, you sort of gum them up, or you have a little bit of an
immune response, and you get rid of them.An immune compromised person, though,
(09:20):
can't always do that. And one of these fungi has the added feature that, unlike most of the others,
it actually grows well in human conditions. So, it grows well at relatively high temperatures. So,
when people are a bit immunocompromised or sometimes if they get a very high dose,
breathe it in, get infected in the lungs, and then it actually becomes a systemic infection.
(09:45):
The fungi will actually migrate throughout the body. And by the time people realize
that they have symptoms, it's often too late to get very much effective treatment. So even
if you get antifungals, it can be kind of like too late. So, there's a pretty high mortality.
So that's one of those, that's Talaromyces marneffei, it's restricted to Southeast
Asia. It seems to have evolved within perhaps another mammalian host. It's really common in
(10:10):
bamboo rats. So, some of these things that end up making it more virulent in people are probably
evolved in response to these other mammal hosts, but it still produces tons of spores,
and it's in the air. It's just that when people are immunocompromised, so during HIV epidemic, the
infection rates for that got really, really high.So, what we were trying to understand was what's
(10:34):
the ecology of this organism? It seems to maybe be asexual, but it's not really asexual. And the
diversity of infections depends partly on the diversity of the hosts in those locations. So,
we were trying to understand the epidemiology of that disease.
The other organism (10:55):
Penicillium rubens, Penicillium chrysogenum, or Penicillium floreyi,
any one of these names that you might want to use for penicillin producing Penicillium species,
that's the other fungus that I was working on at the time. So, this one is everywhere,
everywhere, like pretty much anywhere in the world you go, you're going to
(11:16):
be breathing it in at some frequency.And I was based at Imperial at the time,
and I was based at the Saint Mary's campus, where Alexander Fleming initially isolated his fungus.
So, we were working with the Fleming Museum on some original material that they had from
Alexander Fleming. We were trying to work out, was he really lucky when he isolated that fungus? And
(11:40):
we were also trying to resolve some issues around the evolution of that group of fungi. There's some
sort of unexplained variation, how can something actually be everywhere? How is that possible?
It's pretty hard to imagine a species being cohesive across that level of geographic space.
And how can there be so many species that are closely related to each other,
(12:04):
all of which seem to be everywhere, right? Like what's keeping them separate as species? So,
we were interested in trying to answer more evolutionary biology questions,
a little bit of ecology questions, and the framing was around Alexander Fleming. But the questions
were really about, how is this organism doing this kind of biology? And is that related ultimately
(12:27):
to the kind of interactions it has with other microbes? Right, it makes these antibiotics. Is
part of being a globally distributed fungus, having different antibiotic interactions,
different competitive interactions with other microbes, an important feature?
So yeah, two related, so Talaromyces marneffei used to be called Penicillium marneffei. So,
(12:49):
it used to be sort of a pair of Penicilliums that I was working on, but much more focused on things
that matter to people at that stage.So, what are you working on now?
Now, in my lab we have projects that are working on endophytic fungi. So,
fungi that live inside of plants that don't show any symptoms. We're interested in how
(13:14):
that shapes what people expect out of those plants. So, whether they eat them or whether
they shouldn't eat them, whether those fungi can be used to suppress the growth of plant pathogens.
We're also working on fungi as building materials. So, I collaborate with people in
the engineering side of the university, where we grow fungi to act as insulation materials.
(13:40):
And then most of the work in the lab at the moment is focused all around this one species of yeast
called Metschnikowia pulcherrima. One of those stories is actually related to doing evolution
with high school students. So, we've franchised out some of Maitreya Dunham's work, where we
actually bring this yeast to high school students, and they perform evolution experiments. So,
(14:04):
they compete them, see who can make it the most tolerant to acetic acid. And then we come back and
sequence the genomes that they've evolved, and we can look and see what the variants are that might
be responsible for those trait differences. And we can also explore how evolution works overall,
right. So, not every strain has every mutation. How could these strains have identical mutations?
(14:28):
Why would they have mutations in the same gene that aren't identical? So,
we can explore evolution that way. And that's all with Metschnikowia pulcherrima.
But the reason we got working with Metschnikowia pulcherrima in the first place is because,
in collaboration with some chemical engineers here, Chris Chuck in particular,
we actually were exploring how we can make a palm oil alternative using yeasts.
(14:52):
So, grow yeasts on something that's maybe a second-generation kind of feedstock, like wheat,
straw, for example, something affordable, cheap that's not causing any substantial losses,
generate oil that can be used instead of palm oil, and take some of the pressure
off the palm globally, which should be a more sustainable alternative.
(15:16):
Overall, I think yeasts, as producers of chemical and food products, are almost always going to be
a more sustainable choice compared to forestry or to animal products, so we got into it for
that reason and that research is ongoing. That's the other thing we do in my lab. So, we're always
trying to figure out ways to make that better. We do some genetic modification of those yeasts.
(15:41):
We also do a lot of adaptive evolution to push the yeast in different directions.
So, all of that ties together because we think about fungal interactions in pretty much every one
of those cases. So even when we're thinking about making more palm oil, we're also thinking about
how this yeast is interacting with other microbes in these fermentations or how it's feeding back on
(16:04):
itself. So how it's interacting with itself, to change its metabolic responses. So that's
sort of an overview of what we do now.So, are you working on any bad fungi?
Oh, I have one bad fungus that always stays around the lab. We work on this fungus called
Basidiobolus. I'm just going to leave it at the genus name. And it is relatively rare as an
(16:27):
infection. It shows up in some epidemiological events, so there will be outbreak cases,
but it's found pretty widely across the world.It's extremely common in amphibian and reptile
guts. So, if you go out there and grab some frog poo and send it to me,
probably about half the time I'm going to be able to get Basidiobolus to grow out of that,
(16:50):
wherever you've got your amphibian from.And sometimes it infects people in
different ways. The most common way is sort of subdermal infection. So,
somebody gets a big lump growing and that's unpleasant, usually not life threatening, but
it can be a really bad infection when it's in the guts. So, it lives in in amphibian guts normally,
(17:11):
lives in reptile guts normally, but it shows up in human guts as a pretty difficult case to treat.
So, we're interested in it as a disease organism, but we're also really interested
in it because maybe it has an important ecology role in the guts of animals. We
also think that it has a really challenging evolutionary history. So, it's a fungus that
(17:35):
we can't really put in one of the major groups within the fungal lineage very effectively,
so we're interested in it phyla genetically.So, we still do some work on that in the lab,
but that's like me and some undergraduates doing that work, no PhD’s, no funded work looking at
Basidiobolus at the moment. But yeah, maybe soon.So, you have a new paper coming out. What have
(17:59):
you been looking at and what did you find?Okay, so the new paper is about fungi in
microbiomes. It's particularly about using fungi as probiotics in microbiomes. The question that
we were initially challenged with is, what makes a good probiotic? My PhD student was
(18:23):
concerned that we were putting in a lot of effort on very few strains of the usual suspects, trying
to figure out what might be a good probiotic, and he thought there might be a better way to do this.
So, what we were interested in trying to do was using metabolic models. So,
models based off of genomes to determine how organisms would interact, in a host.
(18:50):
And if we added a fungus to this community of microbes, would it be beneficial? Would it
be a negative effect? And could we look across all the fungi really, and say which ones are good and
which ones are bad, based on these metabolic models. So that's essentially what we did.
(19:12):
It’s a very computationally intensive approach, but what we found was, fungi matter. So,
if you add them to these communities, they change the trajectory for the microbial communities
overall. We found that small differences on a sort of phylogenetic scale can have really
big differences in outcomes. So, two strains of Saccharomyces might have very different effects,
(19:39):
as different between those two strains of Saccharomyces, as you might see between
those yeasts and some mushroom like fungus.Another thing that we discovered was some fungi
are really good, and some are really bad. So, we looked at good and bad in two different ways. We
tried to figure out if the fungi were supporting the microbes that we expect to be good players
(20:02):
in these microbiomes, and then we also did a second measure of whether they're good or bad,
by also adding in pathogenic microbes and seeing whether they suppressed the invasion
of pathogenic microbes. Some fungi actually like helped the pathogens do better, and some
fungi are really good at excluding them, right. And so, we found a large amount of variation.
(20:25):
The other thing that we discovered that I think is really important and isn't exactly about fungi,
but it is about these metabolic models, is that small differences in the diets of hosts have a
huge impact on these outcomes. So, a probiotic for one diet can become an anti-probiotic in another
(20:47):
diet. We were actually focused in agriculture where you can really have pretty good control
over what your chickens for example, are eating. So, I think that's another result for us, was just
showing that these are the environments where it might make sense to use these kinds of approaches.
So, what's next for you?What's next for me? Antifungal
(21:09):
resistance is a major problem and it's getting worse. And it will continue to get worse for us
as the climate changes. So, I think that's the other direction that our research will start
to shift. And each of the projects that I've talked about can be involved in that. But I
think that we're going to focus a lot on how we can relieve some of that pressure and how
(21:30):
we can make predictions about what's going to be difficult in the next few decades.
So, talk to me about this, because it sounds like it's really important,
antifungal resistance, talk me through that?Okay. Well, as I started with, fungi are more
closely related to animals than they are to plants or something else. And that has some problems for
(21:51):
us, because if we make a drug that targets fungi, it also targets animals, which is us. And also,
fungi don't have very many things that makes them uniquely fungi, so we don't have
very many targets that work for a lot of fungi.So, most of the drugs that we use are targeting
very few sites and fungi. We only have a handful of antifungals that are safe to use in people.
(22:16):
And the same sites that get targeted by those drugs are also the ones that get targeted by
things that we use to suppress fungal growth in crops. Important, we lose, you know, billions of
pounds a year to crop damage and crop loss, and we need to be able to eat that food. So,
we're going to have to keep treating for fungi in the fields. So those two things put a lot of
(22:40):
pressure on very few functional antifungals.So, the challenges that are emerging are that
those aren't working so well anymore. Fungi have these mega sized populations; they rapidly evolve
resistance. Even more problematically, some of the resistance mechanisms that they evolve are
kind of like generalized resistance mechanisms. So being resistant to some antifungal treatment
(23:07):
is the same kind of process that makes them salt tolerant for example. And as the climate changes,
we're going to have more of these issues around, you know, climate change leading to fungi that
are already resistant to the things that we would use as antifungals. So, there's a lot
of pressure to both discover new antifungals and to figure out how we can stop making it worse by
(23:32):
putting, you know, more pressure on fungi.There is another element of climate change,
which is that most fungi don't really grow at high temperatures, like mammalian body temperatures,
very well, certainly here in the northern hemisphere’s higher latitudes. And as climates
warm, more of these fungi that we do interact with are going to get exposed to warmer temperatures as
(23:53):
well. And that's going to lead to novel fungal infections emerging. And we kind of need to
be prepared to deal with that. Some of that, again, is novel antifungals. Some of it is just
understanding how those fungi are going to change in response to temperature, so that we can figure
out if there are other ways to manage them.So, it really sounds, talking to you that
(24:15):
you're really on a frontier with fungi, because there's so much that we can learn about them.
Yeah. So, I would say every mycologist out there is on the frontier, because there's so
much unknown for the amount of work that needs to be done. We have far too few people studying
(24:35):
fungi, I would say. Yeah, I don't know any mycologist who isn't on the frontier of
research. I think everybody out there who's trying to make an advance on fungi is having
to push into unexplored space. The community is relatively small compared to the problem.
Dan, thank you so much for talking with me. This was a podcast by the Milner Centre for
(24:58):
Evolution at the University of Bath. I'm Turi King and thank you for listening. If you have
any thoughts or comments on this or any other episodes, please contact us through social
media. For more information about the Milner Centre for Evolution, you can visit our website.
Hello and welcome. You are listening to a podcast by the Milner Centre for Evolution
at the University of Bath. I'm Professor Turi King, your host, and today I'm talking
to Daniel Hank, whose research focuses on the evolution and ecology of fungi. Dan,
for those who don't know, what are fungi?Well, fungi are organisms relatively closely
(00:30):
related to animals. Sometimes they're called a kingdom of fungi. And they are difficult
to pin down with, like, a synapomorphy. The ones that we know the best will be mushrooms,
but also yeasts, right. So, yeasts that we use in baking and fermentations of all sorts, beers,
(00:50):
and wines. Those are the fungi that we're most familiar with. But there are fungi everywhere.
So even the mushrooms you think about as the fungus. But in fact, most of the mushroom fungus
is down there in the ground and growing completely out of sight and busy being a microbe for almost,
you know, all of its life, except for this little flash in the pan where it makes a big mushroom.
(01:14):
Other fungi that people run into all the time are in their bathrooms, where it's like this mould
on the walls or in their kitchens where it's mouldy food, or occasionally on the outside of
your cheeses, which is really delicious.So, fungi are all around and you can't
really avoid them, humans interact with fungi all the time. But what they are,
(01:36):
that's a trickier question for me, because there's no thing that we can point to and say, that's
what a fungus is. But in a lot of ways, even though they're more closely related to animals,
and they were studied as plants for a long time, they're more like bacteria in a lot of these ways
when we think about how much diversity there is.So, what's their place in the
ecosystem? What do they do?The main thing about fungi is they
(01:56):
eat outside of themselves, right. So, they secrete enzymes that adjust their surroundings, and then
they absorb the nutrients from that. So, they are functional as decomposers, often. So, they're out
there in the soil mixing it up with bacteria, sort of degrading stuff and eating it that way.
They also form symbiosis, which I think is one of the key ingredients for fungi. So,
(02:19):
they form important symbiosis with plants, mycorrhizae, which many people will have heard
of this wood wide web that gets talked about sometimes where fungi are down in the ground,
connecting trees and plants of different sorts. So, they form a special relationship on the
outside and inside of root tips, and then go out and forage for nutrients that plants can't
(02:40):
get. In exchange they get carbon from plants.Fungi are also in the air you're breathing right
now. So, they're kind of in every environment that you can think of. They're in aquatic systems as
well, especially again, like decomposing but also as parasites. So, for every symbiont out
there that's living in a mutualistic relationship, there's a symbiont out there that's busy taking
(03:03):
advantage of a host and being a parasite.Yeah, fungi do all kinds of things. They
live inside of organisms; they live outside of organisms. They live on their own, they live
up in the space station because you can't get rid of it. They live in Antarctic ice. You can
find fungi from ice cores going back millions of years. So, they're kind of in everything.
(03:25):
So, the more I read about this subject, the more I realize just how extraordinary they are. So,
what was it that got you into studying these?Oh, yeah. Purely a person, not actually the
organism so much at all. So, I managed to get a job working with Meredith Blackwell,
who is a fantastic mycologist, and she started me doing a bit of research on
(03:49):
fungi that live on the outside of termites.So, these are like really tiny. These are like,
you know, a 10th of a millimetre in length. So, they're pretty much invisible unless you get them
under a microscope. But they're part of a group of fungi that's incredibly beautiful. So, they come
in a variety of shapes. They're one of the only groups of fungi that has determinate growth. So,
(04:11):
they don't just go on and on making hyphae, they come like in a predetermined set number
of cells that they're going to make. And they look kind of like tiny, microscopic peacocks
stuck on the outside of insects. Really, really weird, but also really beautiful.
And I was working with her and a postdoc in the lab at the time, Alex Weir, and we were sort of
(04:37):
cataloguing these things and trying to answer questions about them, including finding new
species of them. It turns out there are a lot of new fungal species to discover, but at the time,
I was just so excited. I felt like I was on the frontier of something that was new,
and I was one of like five people in the world that had ever seen this before,
(04:58):
right, it felt so exciting to me.And Meredith is also an extremely charismatic
person and a cheerleader for fungi, and I was sucked into many fungal things because of her,
like the fungi were beautiful, and that was cool, but it was because of her, really, that I did it.
So how did you come to be working on what you're working on now?
(05:20):
So, I was super excited as an undergraduate about fungi. Meredith got me very interested in these
kind of, like, unique things and feeling like I was on the cutting edge of something. And when I
was thinking about going to graduate school, she guided me to Duke, where I was going to work with
my professor, Rytas Vilgalys. He's well-known as a mushroom researcher, at that time that's
(05:43):
most of what his lab was doing. And Meredith and I were talking about what I could possibly
do that would still be, you know, exciting to me because I really like these things that live with
insects. And she pointed me in the direction of this fungus that infects scale insects.
So, I don't know whether you're familiar with scale insects, but these are armoured scale
(06:05):
insects, so they have a pretty depressing life. So, they emerge from an egg, crawl around for a
little while, but then they settle down on the outside of a plant, and then they lose
the ability to crawl or anything, and they're stuck on this little spot on a plant, and they
turn into a giant blob with their mouths down in the plants, feeding on specialized plant cells.
(06:25):
But they're good targets for fungi because they just sit there and they aren't going anywhere,
and fungi can grow in them. And what the fungi that I worked on did was infected scale insects
at that crawler stage and then grew inside of them, but didn't actually kill the insects. So,
they actually kept the insects alive but proliferated inside of the insects. So,
(06:50):
that rather than being a blob of insect, they were a blob of fungus, still alive, still feeding on
the host plant, still doing all their stuff, but never able to reproduce. So, this is bad fitness
for those individual insects that are infected.But with the fungus also does is it grows out of
the individual infected insects and makes a giant mat, kind of like a lichen, over a whole colony
(07:15):
of insects. So, within this mat of fungi, this animal lichen, you'll have some infected insects,
but also a lot of uninfected insects that are then embedded in this protective layer of fungi.
So, this was really exciting to me. And I was like, okay, we're going to work on this as a PhD
project. So, I went with my curiosity to do that, and I was really excited about symbiosis. But by
(07:41):
the time I finished my PhD, I was a little more jaded on just the pure excitement of that science,
because I did so much work on this thing, and I felt like maybe that's not really going anywhere
to make the world a better place. It's really cool and we can find out lots of neat stuff,
and I'm all for that. But I just had a kid, and I was thinking about like,
what am I doing to make this place better for him? And you know, for all of us, and I sort of
(08:07):
shifted gears a bit. And when I moved to the UK, I wanted to work on fungi that actually
infect people or interact more with people.So, I was sort of expanding my horizons from
fungal interactions and weird evolutionary stories to more, fungal interactions that matter to us,
and evolutionary stories and trajectories that affect people's lives. And now I've sort of
(08:32):
continued in that vein. So, I sort of still bring the fungal ecology and evolutionary biology,
but I am very interested in applications with fungi that affect how we live.
So, tell me about these fungi that interact with humans. So,
what were the two that you were looking at and how do they interact? How they affect us?
Okay. So, you're breathing fungi all the time. That is a common feature for both of
(08:58):
these fungi that I was working on. They make ubiquitous spores, they're in the air. And
when you breathe them in normally, a healthy immune system and a healthy person responds,
basically by protecting yourself, you sort of gum them up, or you have a little bit of an
immune response, and you get rid of them.An immune compromised person, though,
(09:20):
can't always do that. And one of these fungi has the added feature that, unlike most of the others,
it actually grows well in human conditions. So, it grows well at relatively high temperatures. So,
when people are a bit immunocompromised or sometimes if they get a very high dose,
breathe it in, get infected in the lungs, and then it actually becomes a systemic infection.
(09:45):
The fungi will actually migrate throughout the body. And by the time people realize
that they have symptoms, it's often too late to get very much effective treatment. So even
if you get antifungals, it can be kind of like too late. So, there's a pretty high mortality.
So that's one of those, that's Talaromyces marneffei, it's restricted to Southeast
Asia. It seems to have evolved within perhaps another mammalian host. It's really common in
(10:10):
bamboo rats. So, some of these things that end up making it more virulent in people are probably
evolved in response to these other mammal hosts, but it still produces tons of spores,
and it's in the air. It's just that when people are immunocompromised, so during HIV epidemic, the
infection rates for that got really, really high.So, what we were trying to understand was what's
(10:34):
the ecology of this organism? It seems to maybe be asexual, but it's not really asexual. And the
diversity of infections depends partly on the diversity of the hosts in those locations. So,
we were trying to understand the epidemiology of that disease.
The other organism (10:55):
Penicillium rubens, Penicillium chrysogenum, or Penicillium floreyi,
any one of these names that you might want to use for penicillin producing Penicillium species,
that's the other fungus that I was working on at the time. So, this one is everywhere,
everywhere, like pretty much anywhere in the world you go, you're going to
(11:16):
be breathing it in at some frequency.And I was based at Imperial at the time,
and I was based at the Saint Mary's campus, where Alexander Fleming initially isolated his fungus.
So, we were working with the Fleming Museum on some original material that they had from
Alexander Fleming. We were trying to work out, was he really lucky when he isolated that fungus? And
(11:40):
we were also trying to resolve some issues around the evolution of that group of fungi. There's some
sort of unexplained variation, how can something actually be everywhere? How is that possible?
It's pretty hard to imagine a species being cohesive across that level of geographic space.
And how can there be so many species that are closely related to each other,
(12:04):
all of which seem to be everywhere, right? Like what's keeping them separate as species? So,
we were interested in trying to answer more evolutionary biology questions,
a little bit of ecology questions, and the framing was around Alexander Fleming. But the questions
were really about, how is this organism doing this kind of biology? And is that related ultimately
(12:27):
to the kind of interactions it has with other microbes? Right, it makes these antibiotics. Is
part of being a globally distributed fungus, having different antibiotic interactions,
different competitive interactions with other microbes, an important feature?
So yeah, two related, so Talaromyces marneffei used to be called Penicillium marneffei. So,
(12:49):
it used to be sort of a pair of Penicilliums that I was working on, but much more focused on things
that matter to people at that stage.So, what are you working on now?
Now, in my lab we have projects that are working on endophytic fungi. So,
fungi that live inside of plants that don't show any symptoms. We're interested in how
(13:14):
that shapes what people expect out of those plants. So, whether they eat them or whether
they shouldn't eat them, whether those fungi can be used to suppress the growth of plant pathogens.
We're also working on fungi as building materials. So, I collaborate with people in
the engineering side of the university, where we grow fungi to act as insulation materials.
(13:40):
And then most of the work in the lab at the moment is focused all around this one species of yeast
called Metschnikowia pulcherrima. One of those stories is actually related to doing evolution
with high school students. So, we've franchised out some of Maitreya Dunham's work, where we
actually bring this yeast to high school students, and they perform evolution experiments. So,
(14:04):
they compete them, see who can make it the most tolerant to acetic acid. And then we come back and
sequence the genomes that they've evolved, and we can look and see what the variants are that might
be responsible for those trait differences. And we can also explore how evolution works overall,
right. So, not every strain has every mutation. How could these strains have identical mutations?
(14:28):
Why would they have mutations in the same gene that aren't identical? So,
we can explore evolution that way. And that's all with Metschnikowia pulcherrima.
But the reason we got working with Metschnikowia pulcherrima in the first place is because,
in collaboration with some chemical engineers here, Chris Chuck in particular,
we actually were exploring how we can make a palm oil alternative using yeasts.
(14:52):
So, grow yeasts on something that's maybe a second-generation kind of feedstock, like wheat,
straw, for example, something affordable, cheap that's not causing any substantial losses,
generate oil that can be used instead of palm oil, and take some of the pressure
off the palm globally, which should be a more sustainable alternative.
(15:16):
Overall, I think yeasts, as producers of chemical and food products, are almost always going to be
a more sustainable choice compared to forestry or to animal products, so we got into it for
that reason and that research is ongoing. That's the other thing we do in my lab. So, we're always
trying to figure out ways to make that better. We do some genetic modification of those yeasts.
(15:41):
We also do a lot of adaptive evolution to push the yeast in different directions.
So, all of that ties together because we think about fungal interactions in pretty much every one
of those cases. So even when we're thinking about making more palm oil, we're also thinking about
how this yeast is interacting with other microbes in these fermentations or how it's feeding back on
(16:04):
itself. So how it's interacting with itself, to change its metabolic responses. So that's
sort of an overview of what we do now.So, are you working on any bad fungi?
Oh, I have one bad fungus that always stays around the lab. We work on this fungus called
Basidiobolus. I'm just going to leave it at the genus name. And it is relatively rare as an
(16:27):
infection. It shows up in some epidemiological events, so there will be outbreak cases,
but it's found pretty widely across the world.It's extremely common in amphibian and reptile
guts. So, if you go out there and grab some frog poo and send it to me,
probably about half the time I'm going to be able to get Basidiobolus to grow out of that,
(16:50):
wherever you've got your amphibian from.And sometimes it infects people in
different ways. The most common way is sort of subdermal infection. So,
somebody gets a big lump growing and that's unpleasant, usually not life threatening, but
it can be a really bad infection when it's in the guts. So, it lives in in amphibian guts normally,
(17:11):
lives in reptile guts normally, but it shows up in human guts as a pretty difficult case to treat.
So, we're interested in it as a disease organism, but we're also really interested
in it because maybe it has an important ecology role in the guts of animals. We
also think that it has a really challenging evolutionary history. So, it's a fungus that
(17:35):
we can't really put in one of the major groups within the fungal lineage very effectively,
so we're interested in it phyla genetically.So, we still do some work on that in the lab,
but that's like me and some undergraduates doing that work, no PhD’s, no funded work looking at
Basidiobolus at the moment. But yeah, maybe soon.So, you have a new paper coming out. What have
(17:59):
you been looking at and what did you find?Okay, so the new paper is about fungi in
microbiomes. It's particularly about using fungi as probiotics in microbiomes. The question that
we were initially challenged with is, what makes a good probiotic? My PhD student was
(18:23):
concerned that we were putting in a lot of effort on very few strains of the usual suspects, trying
to figure out what might be a good probiotic, and he thought there might be a better way to do this.
So, what we were interested in trying to do was using metabolic models. So,
models based off of genomes to determine how organisms would interact, in a host.
(18:50):
And if we added a fungus to this community of microbes, would it be beneficial? Would it
be a negative effect? And could we look across all the fungi really, and say which ones are good and
which ones are bad, based on these metabolic models. So that's essentially what we did.
(19:12):
It’s a very computationally intensive approach, but what we found was, fungi matter. So,
if you add them to these communities, they change the trajectory for the microbial communities
overall. We found that small differences on a sort of phylogenetic scale can have really
big differences in outcomes. So, two strains of Saccharomyces might have very different effects,
(19:39):
as different between those two strains of Saccharomyces, as you might see between
those yeasts and some mushroom like fungus.Another thing that we discovered was some fungi
are really good, and some are really bad. So, we looked at good and bad in two different ways. We
tried to figure out if the fungi were supporting the microbes that we expect to be good players
(20:02):
in these microbiomes, and then we also did a second measure of whether they're good or bad,
by also adding in pathogenic microbes and seeing whether they suppressed the invasion
of pathogenic microbes. Some fungi actually like helped the pathogens do better, and some
fungi are really good at excluding them, right. And so, we found a large amount of variation.
(20:25):
The other thing that we discovered that I think is really important and isn't exactly about fungi,
but it is about these metabolic models, is that small differences in the diets of hosts have a
huge impact on these outcomes. So, a probiotic for one diet can become an anti-probiotic in another
(20:47):
diet. We were actually focused in agriculture where you can really have pretty good control
over what your chickens for example, are eating. So, I think that's another result for us, was just
showing that these are the environments where it might make sense to use these kinds of approaches.
So, what's next for you?What's next for me? Antifungal
(21:09):
resistance is a major problem and it's getting worse. And it will continue to get worse for us
as the climate changes. So, I think that's the other direction that our research will start
to shift. And each of the projects that I've talked about can be involved in that. But I
think that we're going to focus a lot on how we can relieve some of that pressure and how
(21:30):
we can make predictions about what's going to be difficult in the next few decades.
So, talk to me about this, because it sounds like it's really important,
antifungal resistance, talk me through that?Okay. Well, as I started with, fungi are more
closely related to animals than they are to plants or something else. And that has some problems for
(21:51):
us, because if we make a drug that targets fungi, it also targets animals, which is us. And also,
fungi don't have very many things that makes them uniquely fungi, so we don't have
very many targets that work for a lot of fungi.So, most of the drugs that we use are targeting
very few sites and fungi. We only have a handful of antifungals that are safe to use in people.
(22:16):
And the same sites that get targeted by those drugs are also the ones that get targeted by
things that we use to suppress fungal growth in crops. Important, we lose, you know, billions of
pounds a year to crop damage and crop loss, and we need to be able to eat that food. So,
we're going to have to keep treating for fungi in the fields. So those two things put a lot of
(22:40):
pressure on very few functional antifungals.So, the challenges that are emerging are that
those aren't working so well anymore. Fungi have these mega sized populations; they rapidly evolve
resistance. Even more problematically, some of the resistance mechanisms that they evolve are
kind of like generalized resistance mechanisms. So being resistant to some antifungal treatment
(23:07):
is the same kind of process that makes them salt tolerant for example. And as the climate changes,
we're going to have more of these issues around, you know, climate change leading to fungi that
are already resistant to the things that we would use as antifungals. So, there's a lot
of pressure to both discover new antifungals and to figure out how we can stop making it worse by
(23:32):
putting, you know, more pressure on fungi.There is another element of climate change,
which is that most fungi don't really grow at high temperatures, like mammalian body temperatures,
very well, certainly here in the northern hemisphere’s higher latitudes. And as climates
warm, more of these fungi that we do interact with are going to get exposed to warmer temperatures as
(23:53):
well. And that's going to lead to novel fungal infections emerging. And we kind of need to
be prepared to deal with that. Some of that, again, is novel antifungals. Some of it is just
understanding how those fungi are going to change in response to temperature, so that we can figure
out if there are other ways to manage them.So, it really sounds, talking to you that
(24:15):
you're really on a frontier with fungi, because there's so much that we can learn about them.
Yeah. So, I would say every mycologist out there is on the frontier, because there's so
much unknown for the amount of work that needs to be done. We have far too few people studying
(24:35):
fungi, I would say. Yeah, I don't know any mycologist who isn't on the frontier of
research. I think everybody out there who's trying to make an advance on fungi is having
to push into unexplored space. The community is relatively small compared to the problem.
Dan, thank you so much for talking with me. This was a podcast by the Milner Centre for
(24:58):
Evolution at the University of Bath. I'm Turi King and thank you for listening. If you have
any thoughts or comments on this or any other episodes, please contact us through social
media. For more information about the Milner Centre for Evolution, you can visit our website.
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