Anti-infective natural substances

00:00:00: Imagine being in the forest on a beautiful day and taking a deep breath.

00:00:07: Can you smell that scent?

00:00:12: It also comes from the microorganisms in the forest floor,

00:00:18: but these microorganisms don't just make the forest scent.

00:00:22: With the natural substances they produce,

00:00:24: they also provide us with the basis for medicinal substances, for new medicines,

00:00:30: because we need them against new pathogens and pathogens that have developed resistance to old drugs,

00:00:37: and also against diseases that we are not able to cure.

00:00:42: Yet, Professor Christine Beemelmans knows the potential of these bio-coenoses that we find in the soil,

00:00:49: or even in water. She heads the Department of Anti-Infectives from Microbiota

00:00:55: at the Helmholtz Institute for Pharmaceutical Research, Saarland, HIPPS, for short.

00:01:00: Today, we are talking about these huge, diverse communities made up of all kinds of tiny organisms,

00:01:07: about the substances they produce and why they are so interesting for drug research.

00:01:15: How do bacteria and viruses trigger diseases?

00:01:19: How does our immune system defend itself against them,

00:01:22: and what must active substances be able to do to fight dangerous infections?

00:01:29: The Helmholtz Center for Infection Research is looking for answers to these questions.

00:01:34: How this research works, how the results are used in medicine,

00:01:38: and who the people are that do the work.

00:01:41: This you can listen to here at InFact, the podcast of the Helmholtz Center for Infection Research.

00:01:53: I'm here in the Helmholtz Institute for Pharmaceutical Research, Saarland, HIPPS,

00:01:59: with the Natural Products Researcher, Professor Christine Beemelmans. Hi.

00:02:04: Hello.

00:02:06: What are your actually researching here?

00:02:09: My group's research is focused on the microbes, meaning bacteria and fungi,

00:02:14: and we want to find out how these organisms live together,

00:02:19: and especially how they communicate with each other,

00:02:22: and that's what they are normally doing by natural products.

00:02:26: Natural products sometimes sounds a bit like "mangiival" or like "alternative medicine",

00:02:34: but why is it really a highly topical and highly scientific research field?

00:02:40: Natural product research has always been very important, also in the medieval ages,

00:02:46: because that's how they treated patients also at that time.

00:02:50: And you also have to consider natural products are very old.

00:02:53: Bacteria and fungi are very old, and they have producing them ever since,

00:02:58: since they basically developed the capabilities to do so,

00:03:02: and that's dating millions of years back, so they have been always around us.

00:03:07: And I think that's why microorganisms are such good sources of active products

00:03:15: that can be developed into new drugs.

00:03:18: Correct. So they have the genetic capabilities to basically produce these compounds,

00:03:23: and we are taking use of that.

00:03:25: First of all, we want to understand how these microbes interact,

00:03:28: to also understand how beneficial good microbes can actually live in us or in other organisms,

00:03:34: and also how we can use their natural product repertoire to fend off diseases

00:03:39: which are often caused by actually pathogenic, fungi or pathogenic bacteria.

00:03:45: You have already researched natural products in various biosynosis,

00:03:51: for example at the Leibniz Institute for Natural Product Research in Jena,

00:03:56: on termites and hydructenia, aquatic animals that form colonies.

00:04:04: What else can you, where else can you find natural products?

00:04:09: You can basically find them everywhere.

00:04:11: So we chose these two symbiotic systems because they are very old,

00:04:16: so the termite system dates back 40 million years.

00:04:19: So that means the organisms have interacted since then with each other,

00:04:24: meaning the insects together with the bacteria and fungi.

00:04:27: So they have co-evolved and the natural products in the system were anticipated to play a role in the system for a long time.

00:04:34: So we wanted to understand this very, very old system.

00:04:38: The same for the marine system.

00:04:40: Many marine organisms actually developed 100 of million years ago

00:04:44: and have been interacting with bacteria ever since.

00:04:47: So that means natural products in the system probably also very old and have certain functions.

00:04:53: And that was our intrinsic interest in that.

00:04:55: So now looking around us, of course, all our organisms, like us humans,

00:04:59: they have a bacteria which have been there for a long time already.

00:05:03: So meaning they have certain functions and also produce certain natural products which we don't know yet of.

00:05:08: So in the structures we don't know yet.

00:05:10: So now we talked a lot about microorganisms, where you can find them and which products they produce.

00:05:19: But how do you get these products?

00:05:22: Yeah, for that you need actually interdisciplinary team because you need microbiologists

00:05:28: who are capable of cultivating these organisms.

00:05:31: And at the same time you also need analytical chemists,

00:05:34: meaning people who are trained to analyze substances, to characterize them

00:05:39: and also to produce them in such a quality that you can actually do bioassays.

00:05:45: So for that you need people or scientists from various different fields.

00:05:50: But even if I'm not a scientist, I can help find natural products.

00:05:56: How can I do that?

00:05:56: Yeah, we have actually a citizen science project, which was initiated here in this institute.

00:06:02: And you can basically request online a box which contains a sample kit.

00:06:09: We have basically a box for collection.

00:06:11: And then you can just send in these samples and you can collect them everywhere in your

00:06:15: garden, in your backyard, in front of your door, wherever you want.

00:06:19: And then just send basically with the box also the information where you got the sample.

00:06:25: And we will process them here.

00:06:28: Cool.

00:06:29: So I can take a kit with me and send some samples from Cologne.

00:06:35: Yeah, sure.

00:06:36: You can also take several kits.

00:06:37: So how much you like.

00:06:40: And if you're not here, you can request them online and they are being shipped to you.

00:06:44: And then it's also free shipping back to the institute.

00:06:47: This is a good service.

00:06:50: But the incredible number of different species and therefore substances or products that

00:06:55: you can find, how many products are actually researched further and how many of them end

00:07:02: up becoming drugs?

00:07:03: Yeah, that's a good and critical question.

00:07:08: Of course, first of all, when we identify natural products in the settings of our systems

00:07:14: or also within other groups, they can have different functions than natural products

00:07:19: because they were not made by the organisms for our purposes.

00:07:22: But we want to modulate them so that we can use them further.

00:07:27: So there's very difficult to say a number to it.

00:07:30: But at the end, if we have, if we fill the pipeline with enough compounds, the probability

00:07:35: to actually get drug leads or compounds for a certain aim, it's increasing.

00:07:40: If you don't fill the pipeline, we will not get any candidates.

00:07:44: So at the end, if you have, for example, 1000 compounds and you end up with two, three very

00:07:49: promising drug leads, that's already something.

00:07:53: So it's basically like a reverse pyramid.

00:07:56: So if you fill in a lot of compounds, you will at the end also end up with a couple of

00:08:00: compounds which can then go into preclinics or even further.

00:08:04: But I think it's a huge database.

00:08:08: How is that managed?

00:08:09: Yeah.

00:08:10: We, of course, every group has its own data management, but we also have basically a collection

00:08:15: of strains where all of the HZI, all of the people who are belonging to the center can

00:08:22: retrieve from.

00:08:24: Also the data related to the natural products itself can be basically retrieved by the groups

00:08:29: or requested.

00:08:30: So if compounds are, for example, showing promising activity in one direction, they can also be

00:08:36: explored into other directions.

00:08:38: So data management is always a very important aspect so that not something lands in a rubbish

00:08:44: bin just because nobody knows about it.

00:08:49: You mentioned the HZI.

00:08:51: How does your work here at the HIPPS relate to the work of your colleagues at the HZI?

00:08:59: It relates very much because we are also researching on common topics.

00:09:03: So for example, in the group of Mark Stadler, they are very interested in fungal natural

00:09:07: products and their bio activities.

00:09:10: So that relates very much to exploring also different sources, also taxonomically unique

00:09:15: sources.

00:09:16: And these natural products are also important for screening here.

00:09:20: Or we are also working on certain fungal taxa, which are of importance for them.

00:09:24: So that's very mutual interests.

00:09:27: And for example, in the topic of chemical biology, once we have natural products of

00:09:31: importance with important scaffolds, they can be processed further synthetically, semi-synthetically

00:09:37: in the group of, for example, Mark Brunstrup, or further develop for the mode of action

00:09:41: studies.

00:09:42: Wow.

00:09:43: But you did not only research here in Germany, but also in Japan and in the US.

00:09:52: What could we learn from them and what could they learn from us?

00:09:56: Yeah, so being in different countries, of course, is an experience everybody should

00:10:02: have or it's a research environment is quite different in other countries.

00:10:07: At the end, of course, we have the Germans saying that everybody cooks with water.

00:10:10: So at the end, the research is done in similar ways.

00:10:13: But the way how we approach this approach to research are different sometimes.

00:10:18: So especially the enthusiasm, the positive approaches to explore new avenues.

00:10:25: That's something, a feature which I find in the US very interesting and also important,

00:10:31: something that I learned there to really go with a very positive attitude towards it

00:10:36: and that we can really make it.

00:10:38: And from Japan, I basically also learned that you really have to be like insisting on problems,

00:10:44: even if you have a little bit to work harder than usual.

00:10:48: But you have to find the balance between both.

00:10:50: So one last question.

00:10:52: In your free time, do you always have a sample tube with you?

00:10:56: Yeah, normally, yes.

00:10:59: So in my free time, I work a lot in the garden or doing sports.

00:11:03: But normally if you go outside, you always have sample tubes with us.

00:11:09: Thank you for the fascinating talk about microorganisms and the natural products they produce.

00:11:14: Thank you.

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