Natural Prodcast Episode 15 – Katherine Duncan

This is Natural Prodcast’s conversation with Professor Katherine Duncan from the University of Strathclyde in Glasgow, Scotland. Dr Duncan’s work focuses on marine microbial chemical ecology. We also discuss Actinobase, molecular networking, and the future of integrated secondary metabolism data.

Links and Notes

Dr Duncan’s group webpage is at medicinesfromthesea.com and you can follow her on Twitter @kate_duncan

If you work with actinomycete bacteria, then you absolutely need to know about, and contribute to ActinoBase.org. It’s a fantastic community-built resource for experimental protocols, media recipes, plasmid maps, useful software tools, and more.

We didn’t discuss it here, but you should absolutely check out the ActinoBase seminar series, and its YouTube channel, with lots of great and fascinating seminars, focusing on actinobacterial biology and chemistry.

Transcript

Dan Udwary: Hey,

Alison Takemura: Hey, Dan.

Dan Udwary: Today we’re going to talk to Kate Duncan. And Kate is– I should ask, you are Kate Duncan? Or do you want to be Katherine Duncan or Dr. Duncan?

Kate Duncan: Oh, goodness. I mean, if you were to find my scientific papers, that would be Katherine.

Dan Udwary: Right.

Kate Duncan: But most people that know me call me Kate.

Dan Udwary: Great. So we’ve got Kate here today, and we wanted to talk to her about a whole list of things. So we have a Scripps background shared together, although I don’t think we overlapped.

Kate Duncan: No.

Dan Udwary: I want to talk about ActinoBase, we want to talk about Antarctica, and we want to talk about molecular networking, because I really enjoyed the review that you wrote with Marnix on putting that stuff together. It’s been kind of a theme, I think, in the last couple of conversations that we’ve had on this podcast, the idea of taking all the different natural products data that there is and putting things, coalescing them, so that we can really make discoveries. And so I’m really excited to have read that review and to have you on to talk about that.

Kate Duncan: Great, I’m super excited! Lots of my favorite areas there, so I’m sure I’m going to have fun.

Dan Udwary: Super.

Alison Takemura: All right, I want to ask the first question. Kate, can you tell me the story of how you got into secondary metabolites?

Kate Duncan: So I always liked science in school. I wouldn’t say I was one of these people that wants to study oceanography and was fascinated by the oceans, though I’ve always lived by the sea in the northeast of Scotland.

It was actually when I was traveling at the end of first year University. Quite a lot of people in Europe do this traveling by train inter-railing around countries. And I was actually in Croatia on a small island off the coast in the Adriatic Sea, and I thought, wouldn’t it be cool to look at these– it was actually marine invertebrates there– but look at these things in the ocean and see those medicines inside them.

And this was, I think it must’ve been about 2001, maybe, and so it was before smartphones and before laptops and everything. And I actually waited– there were internet cafes, but I waited until I was back at University, so it must be about a month, a month and a half later. In September, I went to a centralized computer room, because that was what existed back then, and I searched it. And so it turns out there was someone at the University that I was at that did just this. And I discovered it was called “marine natural products.”

And that person was Professor Marcel Jaspars who was in the Chemistry Department. And I was enrolled in biochemistry, but I thought, well, I’m just going to email this person and go and chat. And so I think I was– I went to University when I was quite young. I just turned 17 when I enrolled into University, so I guess I must’ve been around about 18. And I went to Marcel’s office. And he’s incredibly enthusiastic and gave me a bunch of books, but not books on marine natural products, as such, but things like “Silent Spring” by Rachel Carson, and things about understanding the natural world and how we relate to that. And so I read those and changed my degree to chemistry, so I have an undergraduate in chemistry.

Now when I was in fourth year, we had a choice to do an integrated master’s program that was by the Royal Society of Chemistry. It was the first year that they offered this. And the cool thing about it was that it had an international placement. And as we were the first year, there were only eight people in my class. I should point out that I’m an identical twin, and–

Dan Udwary: Oh!

Kate Duncan: And my twin also studied chemistry, because she switched her degree program from geography to chemistry. So we were both enrolled as undergraduates in the Chemistry Department, which caused no end of confusion. And we actually made up a quarter of the master’s class, because there were only eight people enrolled in this M[aster’s] Chem program.

So she went off to Canada to Queen’s to do a placement. And I went to Florida and learned about marine invertebrates, natural products chemistry. It was really before– or kind of around about when the first genome sequencing was done. But natural products– marine natural products– the field, back then, was very much the chemistry of natural products from invertebrates, mostly.

Dan Udwary: Structure elucidation, yeah.

Kate Duncan: Right, yeah, so kind of traditional natural products. So I did that for my master’s. And then I went and worked in the industry for a few years.

And when I decided to do my PhD, I thought, right, I’m going to learn microbiology. So I went to– this was in 2008 by then. And I’ve never done– I mean, I think I did maybe a couple biology classes in undergrad, but my PhD was an actinobacteria. And I tell all my students this now, but when I started my PhD, I’d never poured a Petri dish. I didn’t know what a thermocycler looked like. I was imagining some massive contraption for amplifying genes. I wasn’t really sure what actinobacteria were.

Dan Udwary: Yeah, this all sounds very familiar.

[LAUGHTER]

Kate Duncan: Yeah, and I just went for it. And it was fascinating. And I fell in love with actinomycetes. I loved approaching biology from a chemistry background.

Dan Udwary: Mm-hmm.

Kate Duncan: I thought it was fascinating and still do. And that really was the intersection of how I approach natural products, is kind of integrating the biology and the chemistry. And then, yeah, I did a postdoc with Paul Jensen, Scripps Oceanography.

And as I say to people, I just kind of did a big circle of North America. So then I came back and I worked on an EU project, the Scottish Association for Marine Science. And then I started my own group in 2016. And it very much ties in all of those experiences, you know, integrates biology and chemistry.

I don’t define myself, necessarily, as a chemist. I don’t define myself as a microbiologist or a molecular biologist. I’m a natural product scientist. And I think that’s the way the field is going. And it’s quite an exciting space to be in.

Dan Udwary: Yeah, yeah, I would consider myself a bit of that, too. Although we all have our specializations and the things that we dig into maybe a bit more than others.

Kate Duncan: Yep.

Dan Udwary: You know, given that natural products are so broad and interdisciplinary, we can always work in lots of different things. But what would you say is– what do you think is the thrust of your lab, going forward?

Kate Duncan: Yeah, so I guess we’re really interested in accelerated discovery by integrating biology and chemistry together. I think the main way that we do that is trying to understand what’s important in terms of the chemistry produced by microbes. And by what’s important, I mean, like, where they’re from and who they are, and these really quite basic questions that we can only really address with bigger data sets and integrated data sets. So yeah, in terms of, I guess, fields of science, we span across them. But fundamental is the chemistry produced by actinobacteria and what influences that.

Dan Udwary: I want to point out, too, that your website is medicinesfromthesea.com, which is a great website name, and also extremely well-organized, makes doing research on a person very easy.

Kate Duncan: Well, so, I did set this up. And that is actually how I describe what I do to nonscientists. I think it’s quite accessible. I used to do the website. Actually, one of my students, Darren, currently updates it, so I wouldn’t want to take the credit for the organization.

[LAUGHTER]

Dan Udwary: Fair enough. And so you work primarily in actinomycetes.

Kate Duncan: Yeah. I love actinomycetes.

Dan Udwary: Tell us why. I mean, I know, but I think–

Alison Takemura: I want to hear.

Kate Duncan: They’re so exciting on so many levels. So first, I mean, all bacteria are everywhere. But the fact that actinomycetes form spores and can reside in really tough environments kind of adds a fascination from a biological point of view– the fundamental things, like, are we waking them up? Are they metabolically active and slowly ticking away at these extreme environments? I think that’s just incredible to think about.

And then, from an genomic point of view, I mean, I don’t need to say to you, but they’re unprecedented in the terms biosynthetic gene clusters and genome size. And they’re so complex. There’s so much still to understand.

Dan Udwary: Yeah.

Kate Duncan: So they’re also incredibly adaptable. I think there has been some examples of real successes in that area in terms of synthetic biology, but so much still to understand, and a real area of growth for the field.

And then, chemistry-wise, they’re the stars, right? Chemical diversity, the sheer number of chemicals they produce, their ability to evolve, to go with horizontal gene transfer and run with it and produce different chemistry. They’re just incredible. And I love the smell of them.

[LAUGHTER]

I think they look cool. Yeah, I think I’ve made my point. They’re just all around awesome. I should point out that we also have a couple of projects in the lab that also work in microalgae as well. So it’s not just actinobacteria that we work on.

The one thing that I’ve appreciated since starting my own group is these tools, in terms of looking at the chemistry produced by microbes, they’re pretty adaptable to other organisms. And we’ve done that with microalgae. They’re pretty cool as well. A lot of them have looked at applications like biofuels.

Dan Udwary: Sure.

Kate Duncan: But from a natural products point of view, the field is very focused on a few metabolites and doing a kind of comprehensive overview of that has been quite interesting.

Dan Udwary: Tell me more about natural products and microalgae, because I’m not very familiar with that.

Kate Duncan: Yeah, so there’s some blockbuster metabolites, like astaxanthin, that make your farmed salmon pink so that you buy that in the shop. And then there’s some kind of freeze-dried microalgae like spirulina that you kind of buy in health food shops or whatever, in Trader Joe’s, and put that in your smoothie in terms of their antioxidant properties.

And the field is kind of summarized by that. We think they’re good for you, but we don’t know a huge amount of the chemistry. Or we focus on really particular metabolites from either an environmental point of view, in terms of algal blooms and things like this, or from a commercial point of view.

But in terms of the same questions that we’re interested in bacteria, like what influences the chemistry? What tacts are particularly interesting? And then linking that to antibiotics, and do they have antibiotic properties, and the likes has been really, really fun.

Alison Takemura: And then does that also– well, I guess the question really is, do microalgae also produce natural products that can be helpful in producing biofuels? Because you had mentioned this intersection that you also work at.

Kate Duncan: Yeah, so I don’t work on biofuels. Most of the microalgal research has been on biofuels–

Alison Takemura: Oh, I see–

Kate Duncan: But they’re really quite– they’ve got quite a lot of lipids in them. But from an economically viable point of view, they haven’t quite worked. And as a result, there’s been a lot of work on open pond systems and infrastructure and growing microalgae. And to make the biofuels more economic, they also would like to extract some high– what they term “high value–“

Dan Udwary: Right.

Kate Duncan: Metabolites. And those are things like nutraceuticals or antibiotics and stuff like that.

Dan Udwary: Yeah, making biofuels has to be really cost-efficient or you have to extract some other value from the fermentation, right?

Alison Takemura: Right.

Kate Duncan: Right, yeah.

Alison Takemura: OK. And I also wanted to ask about work that you’ve done in Antarctica. I saw that there were some pictures on your website.

Kate Duncan: Yeah, pictures on my website are because I’m part of a global non-for-profit organization called Homeward Bound. I’m a faculty member and I co-lead the science program for a few of the cohorts. So Homeward Bound is a global non-for-profit that focuses on women in science leadership.

So I think we all recognize that there has been quite a lot of work in recent years to improve gender equality of people entering science programs. So actually, the number of women entering science has increased in a lot of fields– still not, probably, 50-50 in things like physics and maths– but there’s actually more women than men in life sciences at the undergraduate level. However, at the leadership levels of– you know, I’m talking of CEOs, professors, and the kind of decision making table– the data is still very unequal.

Dan Udwary: Yeah.

Kate Duncan: And so it’s about that kind of retention of women in leadership positions and doing something proactive about that. So Homeward Bound is a global initiative for women in science leadership positions. And it has quite an ambitious goal to have 1,000 women in the program over a span of 10 years. So typically about 80 to 100 women get selected each year as a cohort to experience this 12-months leadership program, of which the last month is in Antarctica on a ship.

Yeah, so I went to Antarctica in 2018 as a participant in Homeward Bound 2, last year as faculty co-leading the on-trip science program for Homeward Bound 3. And I currently co-leading the science program for the 12-months for Homeward Bound 5 and was meant to be in Antarctica next month. And that’s currently postponed.

Dan Udwary: Aw!

Kate Duncan: What’s also a bit confusing is I also work on Antarctic actinomycetes, actually.

Dan Udwary: Mm-hmm.

Kate Duncan: A lot of this is kind of current work at the moment. We published, I think, one paper so far about isolation of actinomycetes from Antarctica. And we’ve actually been working a way as a PhD student from Costa Rica, a para that’s been doing a lot of this work. And we’ve isolated some rare actinomycetes from sediment cores in Antarctica that have– some of being carbon-dated to kind of 15,000, 150,000 years ago. So this is 1,000, 2,000, 3,000 meters below sea level. And we’ve managed to culture, and in the lab, some rare actinomycetes. So by “rare,” it’s nothing really to do with their abundance. It’s just that they’re less studied than streptomyces, the genus, right?

Dan Udwary: Right.

Kate Duncan: And Pseudonocardia. And we’ve got new species which we’re currently in the process of almost finished characterizing them. We’ve got genome sequences, which are just incredible. We’ve looked at the genes, the biosynthetic gene clusters of those.And they’re just like nothing in databases that currently exist. We looked at chemistry, so it’s really novel. And they’re just really exciting. And it really kind of paints the picture of– a lot of us say, well, we go to unusual places because biodiversity translates to Nobel chemistry. And these do, they really do.

Dan Udwary: Yeah. OK, cool. So let me ask a silly question– are these guys basically living in the cracks of the ice or something? Or are these spores, or what do you think is going on with the way that they’re deposited?

Kate Duncan: So they’re isolated from sediment.

Dan Udwary: OK

Kate Duncan: And I think we’re waking them up. It’s difficult to do that experiment. There’s a debate in microbiology, you can’t really tell once you’ve isolated them, you would have to do in situ studies in Antarctica. So I guess we’ll never know if we’ve woken them up. I guess we’ll never know if we’ve woken them up or if they were slowly ticking away metabolically, way down under the ocean in Antarctica.

Dan Udwary: Right, right.

Kate Duncan: But either way, it’s pretty cool to be able to– what I say to people that aren’t in natural products is it’s discovery. Not many people get to say they do discovery as a job. And nothing is more exciting than going to, looking at Antarctica, and finding stuff that is new, new species, and then looking at the biology of the ones, looking at the chemistry of those. And, you know, I have undergraduates in the lab at the moment in Scotland. And we’ve given them genome sequences of some of these strains. They’re not all Pseudonocardia. There’s other very active actinomycetes. And what a fun way to do an undergrad project, right?

Dan Udwary: Yeah, you’re giving them the hard drugs right away.

[LAUGHTER]

Kate Duncan: Yeah, right.

Dan Udwary: That’s what science is all about, yeah. No, it’s good. So one of the reasons I wanted to have you on is that we haven’t really talked to someone who’s published a lot in what I guess I would call molecular networking. You know, we should probably grab Pieter Dorrestein sometime or some people. But you’ve got a lot of data on that technique. And I find that really interesting– not that I know a whole lot of mass spec– but I find it really interesting to sort of compare, conceptually, that data with genomics and the kind of things that I do with genome mining. And figuring out how to put that together, I think, is really important to the field. And that’s something we’ve been talking to a few different people about. So tell us a little bit about your perspective on that kind of technique and why it’s valuable to you?

Kate Duncan: I think both genome work and chemistry work, you really see that there have been huge advances in both. The cool thing about genomes is you can, well, if your assembly is good, you can see everything, right? You can see the full biosynthetic potential of what you’ve got.

Dan Udwary: You might not know what you’re looking at, but it’s all there.

Kate Duncan: Right? But it’s all there. Like, the puzzle is pretty much complete, might be a few places in the wrong place, but for the most part.

Dan Udwary: Yeah.

Kate Duncan: And that’s really cool and really exciting. But what’s sometimes surprising for people is, like I said at the beginning, even though chemistry has been around in natural products for a lot longer than genome sequencing, when we do a mass spec– a mass spec is like a chemical profile.

Dan Udwary: Mm-hmm.

Kate Duncan: When we generate that, that’s only a part of the picture. And you could be the most comprehensive natural products chemist, and you can use different solvents, and you can use different ionizations, and you can run a lot of, generate a lot of data. And you only have part of the picture. And there’s a few things for that. One, growing the micro-organism– actinobacteria in this case– in the lab, you are only going to– you’re giving it certain nutrients. It’s only going to be able to generate so much chemistry using those nutrients. Then you’re giving it a flask. And you’re only giving it so much oxygen. And you go, well, OK, so now it’s going to generate a subset of that chemistry. And then you decide, well, the experiment’s done in seven days. So I’m going to extract everything in seven days.

Dan Udwary: Mm-hmm.

[CHUCKLES]

Kate Duncan: And then you’re only getting what’s produced in that time point in the lab, under those nutrient conditions, oxygen conditions. Don’t get me started about temperature and all the rest, right. So you’ve only got, like, a subset of chemistry in front of you. And then you have to decide what organic solvents, or what chemistry you can extract out of this liquid culture of bacteria, right? So you maybe choose something like methanol, or ethyl acetate, or something like this. And then you’re biasing your chemistry viewpoint by polarity. And you’re only getting a subset of the chemistry that’s even in that flask in an extract. And then you running it through mass spec, right? So that depends on ionizing, so you’re essentially getting only a subset of molecules that will fly on an analytical instrument and be detected.

Dan Udwary: You’re making me so happy that I’m in genomics.

[LAUGHS]

Kate Duncan: Yeah, right? And, you know, and everyone thinks oh, chemistry is the traditional one. That’s all figured out, right?

Dan Udwary: Yeah.

Kate Duncan: So then you have this chemical profile. And this is a game based on all those limitations. That’s what you’ve got in front of you. And yet it is more data than you can understand, right? So you have a profile and, you know, that’s just one to extract. And you don’t just have one extract, because you’ve done an experiment. So you might have different strains, or you might have given that bacteria different nutrients. Or you might have done a time course. And you might have done the extraction at five days, seven days, 10 days. And suddenly, you’re then comparing a chemical profile with, let’s say, 100 ions in it, to 10 other chemical profiles that also have 100 ions in it.

Dan Udwary: Right.

Kate Duncan: And somehow, you have to make sense of that information. So the cool thing about molecular networking is– there’s two reasons. One, when we originally looked at chemical profiles generated using these highly sensitive instruments, we had to try and figure out what was there.

Like, was it a known metabolite? Was it something new? And we could only do this by comparing it to databases that were quite often commercial, that were quite often owned by mass spectrometry. It was a big problem, cost quite a lot of money. And they were populated over when a lot of people did structure elucidation and isolation fully, which meant that there was low-resolution data. So what that means is that you have a particular metabolite, and it’s got matches to way too many things. And so that’s not very helpful. So that’s one thing. And it’s a really slow process. And you might not have access to the databases and all of that, so that’s really difficult. And then the second thing is you’re comparing these profiles that you’ve generated. And that’s hugely– it’s a huge amount of data, it’s very difficult to do. So molecular networking had advanced the field in two ways.

One, it uses the information of tandem mass spectrometry. So you’re taking each ion, each metabolite, and you’re breaking it into pieces. And then you’re comparing those metabolites based on the pieces they break into. So not only do you get structural information, you get maybe an idea, oh, well, maybe there’s an amino acid, so maybe it’s a peptide, right?

Dan Udwary: Mm-hmm.

Kate Duncan: But then it also gives you more information for comparing things.

Dan Udwary: Right.

Kate Duncan: And you can do that across different samples. And it has a bunch of databases, because it’s community-led, of people that have high-resolution data of known metabolites and also unknown stuff that they’ve also got in their data set. And you can compare across that. So that’s what takes it to the next level is that kind of community. And it’s just– you get more information. You can actually compare things accurately, and you get that community effort of finding out what’s there. And that is what’s needed in order to start matching chemistry to genes. Because I said genes are the whole picture of what could be possible. And we didn’t know how well we were doing before, because we didn’t know what the chemistry was. And that’s still difficult.

Dan Udwary: Yeah, yeah, yeah.

Kate Duncan: Still hugely challenging. But we now have a way that we can start. And that’s really exciting. And so, yeah, sometimes you can find something that you know, a constellation that you can know. And that’s a chemical that you know, and that’s a good starting point. But it’s about kind of looking at all those other stars that you don’t know and getting some meaning from that.

Alison Takemura: And just to make sure I understand, molecular networking is so powerful because you’re linking like with like. And so if you know any one of those within that cluster, you can begin to infer the function of the other molecules.

Dan Udwary: Yeah, it’s–

Kate Duncan: So not necessarily the function, I guess, in terms of, like, they’re related. So they’re like, yeah, there’s some part to the molecule that are similar, and there’s some bits that are different. And sometimes, in terms of biological activities– like antimicrobial or something– sometimes a little difference is enough. Sometimes it doesn’t need to be a huge difference. So even that’s exciting.

Dan Udwary: Yeah, yeah, it feels like there’s a good parallel there with what we talked about with genome mining, Alison, where once you have a few of the pieces in a biosynthetic pathway, you can sort of interpret other things about the things around them. And you kind of build your knowledge from the things, the small pieces that you know, to expand that out. And then you have more things that look like other things. And it grows exponentially, hopefully.

Alison Takemura: Right.

Dan Udwary: If you do it right.

Alison Takemura: Mm-hmm.

Kate Duncan: Yeah, it’s the things that have no relation to anything.

Dan Udwary: So with families of molecules, how far off are we from being able to, say, see biosynthetic pathways? Or can we see a progression in metabolites and metabolite families? Or are we still far off from that?

Kate Duncan: I think we’re getting there. I think it — really, it depends on everyone getting on board, right? It’s like anything in natural products, it’s such a great community to be in. And all the major advances have been because people have pulled together and gone, right, well this isn’t just interesting in my lab. Let’s see if other people find this. I say to my students, marine natural products started in the ’70s. So who gets to say they work in a field that started in the ’70s right? Not only is that cool, but think about where the field has going in just those few decades. It’s gone from looking at marine invertebrates, it’s gone from traditional natural products chemistry– both of those things have still very much done to be excellently.

Dan Udwary: For sure.

Kate Duncan: Not that they’ve been forgotten. But we’ve also added in microbiology, added molecular biology, genome sequencing, high resolution chemistry data, all mixed by infrared. God, that’s exciting, in a few decades, right? I think the power is in the community. If you look at the field of natural products, it’s on exponential fees for sure, right? Because suddenly it’s kind of like when the internet first started, and you go, whoa, those people are also doing this in this other country?

Dan Udwary: Mm-hmm.

Kate Duncan: Right? And it’s like that for science, not just natural products, but suddenly we have platforms and we have community sharing of data. And we can start going, right, well this thing is in my extract library in a freezer in Scotland. And, you know what, it’s quite similar to that other molecule that you’ve isolated in Canada from this other thing that’s totally biologically different. And that’s what’s cool about the chemistry. It’s putting all that together and going, you know, actually, there’s these huge surprises with linking the biosynthesis and the chemistry and those are all really closely related things in terms of, like, evolution, in terms of taxonomy– produced really different chemistry.

Dan Udwary: Right.

Kate Duncan: Right?

Dan Udwary: Yep.

Kate Duncan: And there’s molecules that are identical or very similar that are isolated from different parts of the world. And I don’t know if they’ve evolved separately or gone through common ancestors or whatever. But putting all of that together is really exciting. And why chemistry is so far behind in that stage is it’s still really difficult to do natural products chemistry. I get asked a lot about modern or mixed approaches, and we use a lot of those in my group. But, ultimately, you still need structure information. You still need structure at this stage, and you still need to put that information into databases so people can identify things. And you can do that with mass spec to a certain degree, but it’s only relying on that historic information or the data that’s generated really slowly, because it’s really difficult.

And that’s one thing that I really like to see is that the traditional is still hugely important, even in the omics era, right. And it’s integrating all of that together that will be the power in the data, molecular families, biosynthetic families. What’s important, then we can start asking big picture questions, like what should I look at? How should I grow it? Is day seven a good day for that species? Yeah, it’s fun.

Dan Udwary: Well, maybe that leads us into techniques. And I definitely wanted to make sure that we talked about ActinoBase. Tell us about ActinoBase and how that project started. And I think it’d be a good thing for our listeners to know about and to participate in.

Kate Duncan: Yeah, for sure so, ActinoBase.

Alison Takemura: What is ActinoBase?

Kate Duncan: Yeah, so that’s a good question, awesome. So ActinoBase is a community initiative that was really a conversation at the Microbiology Society Annual Conference, which happened in Belfast a couple of years ago. And anyone that works on, particularly with Streptomyces, but any actinomycetes, knows that there’s a bible by David Hopwood. I referred to it as a bible because anyone that does anything with actinomycetes has worked in a lab that has a copy of this that’s dogeared.

Dan Udwary: Yeah, of a certain age, yeah, I could picture–

Kate Duncan: Yeah, of a certain age, for sure.

Dan Udwary: –with the yellow and orange blobs on it.

Kate Duncan: Yeah, so I feel like this is a bit of a defining– like you said, a generational thing.

Dan Udwary: It’s a totem for our field, yeah.

ate Duncan: Yeah. And this kind of just ties in with what I just said, this was the go-to for protocols for how to do things, how to work with these really complex and incredible microorganisms. And it was decades-worth of top level researchers putting their ideas how to do this on paper. And so the issue with that is, I’ve just said, the field advances really quickly. This book just can’t keep up. You would need, like, a new addition each month or something, right?

And so the idea was to kind of make some kind of electronic– not to replace the book– but just as a way for researchers, just now, to access protocols and share them among– I like to think we all recognize that there’s people that are doing incredible, world-leading science. But sometimes you have to wait a little bit until the paper comes out before that’s successful. But the other thing is that there is a whole bunch of information that maybe never makes its publication. And these are little tips, you know, how to grow things, or certain nutrients, and media, that there’s a good tip, or certain plasmids that are– so it was a bit of capturing all this information. And so there was– it’s by no means me that did this.

Microbiology Society got behind us on this and decided to kind of champion this as the way forward for people who worked on particular microorganisms. And there’s a group of PIs across the UK that were involved in the initial discussions. But we all nominated PhD students in our lab. And it’s all those PhD students that are ActinoBase. It’s not the PIs. It’s them that do it. They created the Wiki. They edit the pages. They add the content. They run the Twitter account. They run the fantastic seminar series, chaired, and the speakers were all early career or mostly early career researchers. They have the ideas. And they say, wouldn’t it be cool if there was a page on this? And they add it. And they did a review paper of actinobacteria, some advances. All the authors and that are PhD students.

And I think it’s a really nice model. I’d like to see more of this. It’s their ideas. So, sure, there’s some PIs that were maybe involved in initial discussions, but we’re not the ones to take credit of this. And that’s really cool. And I think that it’s so nice to see something that is just early career, you know?

And it spans biology, chemistry, bioinformatics. And increasingly, they’re really trying hard to make the community more accessible across the world. I think we can all recognize that, in terms of diversity, in terms of inclusion, there’s certain countries that are always featured in natural products and actinobacteria research.

But there’s some cool stuff going on elsewhere. And maybe those people don’t make it to meetings and the likes, and they did that across different time zones. They varied the time of the seminar speakers, they really tried to promote it in different countries, in different regions. And I think that’s cool.

Alison Takemura: Can you predict the future for us in terms of what you see on the horizon for natural products and their discovery?

Kate Duncan: Wow, that’s a pretty epic question, awesome. Yeah, you know, again, I think it’s about integrating what we do in the lab with the environment. I know that was kind of a big, big answer, but it’s a big question. At the end of the day, all these natural products are produced for a reason. Every time we go and biodiscover and find things from the environment and culture things under lab settings, we’re getting a snapshot in an artificial environment. And if we really want to accelerate the discovery of new chemistry, and we want to understand the antimicrobial-resistant era, we need new chemistry.

If we want to stop finding stuff that we’ve found, or finding stuff that’s similar to things that we already know, then we probably need to start looking at all that space in the data of– if you look at molecular networks and how much is characterized and how much is unknown, we need to start understanding that. And that’s really difficult to kind of go into that unknown space. So there’s unknown space in our existing data set, and then there’s how to access that and what impacts it in terms of the ecosystem and the environment. And I think that’s the challenge. And it’s daunting, but, you know, there’s so much to discover. 70% of the world’s surface are the oceans. If you look at actinobacteria diversity, I mean, we’ve just found new species in Antarctica.

So there’s the biology discovery. And I’ve just spoken for length about how complex access in chemistry is and how much is unknown. No one is going to be out of a job in terms of things to do anytime soon. There’s a lot, still, to discover.

Dan Udwary: A lot of science, that’s for sure.

Kate Duncan: For sure.

Dan Udwary: Well, I think that’s a great place to wrap things up. This has been–

Kate Duncan: It was fun, you know?

Dan Udwary: –a really fun conversation. Yeah, thank you so much for joining us. And–

Kate Duncan: I’m looking forward to hearing how Scottish I am. [LAUGHTER] Anything that I do– you know, you hear yourself different from how you speak.

Dan Udwary: Yeah.

Kate Duncan: And any time I hear a recording, I’m like, god, I’m so Scottish.

[LAUGHTER]

But I try to speak slowly so that– I don’t know if I managed. But that was me speaking slowly, so you’re welcome.

Dan Udwary: OK, thanks very much.

Alison Takemura: It was very clear.

Dan Udwary: This was great.

Alison Takemura: Yeah.

[LAUGHTER]

Yeah, this was so much fun, thanks again, Kate.