Episode 16 of the Modern Chemistry podcast dives back into glycobiology and its practical application with Benjamin Schumann.
Episode 16 of the Modern Chemistry podcast dives back into glycobiology and its practical application with Benjamin Schumann. Ben is a chemical biologist who studies the biology of carbohydrates (glycans). After completing his undergraduate biochemistry studies in Tübingen, Germany, he was trained in synthetic carbohydrate chemistry in the lab of Peter H. Seeberger at the Max Planck Institute of Colloids and Interfaces Potsdam and the FU Berlin. Developing vaccines against pathogenic bacteria based on synthetic glycans, Ben learned to apply his compounds in biological settings in vivo and in vitro. For his achievements, he received the Award for Excellence in Glycosciences and, in 2017, the prestigious Otto Hahn Medal by the Max Planck Society.
During his postdoctoral work in the lab of Carolyn R. Bertozzi at Stanford University as an Alexander von Humboldt foundation Feodor Lynen fellow, Ben developed an interest in "precision tools" to study glycosylation of human cells in great detail. He started as a Group Leader at the Crick and Imperial College London in 2018.
Towards the end of the show, Ben mentions a prize. Ben and colleagues from Imperial College and Stanford University were awarded the Royal Society of Chemistry's new Chemistry Biology Interface Division Horizon Prize, the Rita and John Cornforth Award. For more details, please check out this link on the Francis Crick Institute's website - https://www.crick.ac.uk/news/2021-06-08_research-prize-for-chemical-toolbox-to-study-the-role-of-cell-surface-sugars.
You will hear the following terms used during the interview. I've included some descriptions here.
Please note, this transcript (provided by rev.com) has not been reviewed by the podcast presenters or guests for accuracy.
Paul Orange: Hello and welcome to the Modern Chemistry Podcast, with your host, Paul Orange. Hello there and welcome to episode number 16 of the show. This episode we dig back into glycobiology, and I think this makes a really nice companion episode to our interview with Elisa Fadda, [00:00:30] which we put out a few months ago.
Today's guest is, uh, Dr. Benjamin Schumann, who is Head of the Chemical Glycobiology Lab at the Francis Crick Institute in London. Um, Ben's working on really trying to interpret the glycobiome, the glycoproteome, using a series of precision tools, um, that really help him dig into how sugars [00:01:00] on protein molecules impact the processes of living cells.
I would really strongly recommend that you check out Benn's website, and in particular follow through to look at some of the publications listed there, as the graphical description of the tools he uses, and the experimental approach is, uh, very easy to understand. Maybe it comes across a little bit more straightforward [00:01:30] than trying to describe it in audio. But, that said, this is still a really great discussion. Uh, Benn talks about some of the challenges in working in glycobiology, um, but also some of the great opportunities that lie ahead with what is a relatively untouched field, and where there's a lot still to study.
So without any further introduction, I'll just hand you straight over to the interview with Benn and I'll be back right at the end to say goodbye. [00:02:00] So welcome to the Modern Chemistry Podcast, and I am delighted to welcome our guest this time, and it's Benn Schumann. And Benn is a Group Leader at the Francis Crick Institute in London and also has a lecture position at Imperial College. And he is a physical science group leader, heading up the Chemical Glycobiology Lab at the Francis Crick Institute. Benn, welcome to the show. Thanks for joining us.
Benn Schumann: Thanks for the invitation.
Paul Orange: Uh, looking into the research you do in the area that you work in, i- it, it's, it's one of those areas [00:02:30] where you could spend forever reading about it and, you know, i- it's super interesting. A, a topic we often get onto towards the end of these shows is, you know, how science is really interdisciplinary these days. But maybe I'd like to start there, because that was one of the things that really struck me about what you do. My, my take on it was you've got hardcore biochemistry at the center of what you do, but there's chemistry, there's, you know, biology, there's disease.
I mean, there's so much stuff [00:03:00] going on here, so how do you think about that and the, the connectivity of everything that you work on?
Benn Schumann: Well, carbohydrates are an interesting topic, when you get into multidisciplinarity, because ... and this is becoming more and more obvious, because we have so amazing techniques to understand other biomolecules. Right? We can sequence DNA using them, so we get a good idea into the genomics. Uh, we, we have great tools to analyze the transcriptome and we have great tools to analyze the proteome. [00:03:30] But glycosylation is still kind of a worst fear somewhere in between these, um, and that's despite kind of decades of amazing work by colleagues, who have kind of really pioneered work into the glycosciences.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: But, m- many of these techniques are really not that amenable to studying glycans, at least not in kind of the throughput and the sensitivity that you would, um, look into proteins, and, and-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... like acids. And so I think, compared to [00:04:00] other biomolecules, chemical tools probably have a bit of a higher significance.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, but also, some of the challenges associated with analyzing glycans, um, make it possible that once you develop a tool for glycobiology, a chemical tool, and you kind of, you know, invent a new tag or a new reagent or so, it's almost very easily transferable to other biomolecules. I think it's fair to say that.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And so if you optimize something that works for glycans, [00:04:30] it probably also works for many other small molecules and biomolecules. And so, so I think that's where the role of chemistry comes into play.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: But at the same time, there's still so much we don't know, that, you know, through quite small steps in chemical innovation we can continue to take huge strides forward in understanding how processes work. And so my own experti- or my own background comes into this, because I, I studied [00:05:00] biochemistry initially. Um, and that was mainly because at school I was interested in kind of, uh, metabolic pathways and so on. And I thought biochemistry is way too dreadful. Um, but I also had macrochemistry, and so that was even further developed through bio- through studying biochemistry, because I was lucky enough to be in an undergraduate course, which was quite chemistry heavy, especially in org- in organic chemistry.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And so I was able to develop this a little bit further. And then in my, um, PhD I wanted to do something that's really, [00:05:30] you know, hardcore chemical synthesis. And so I joined the lab of Peter Seeberger in Berlin, where, um, who, uh, supported me in kind of the desire to go from biochemistry to chemical synthesis and see, well, we'll see where you go, where you go. And I think we were both happy with the outcome of this.
Paul Orange: (laughs)
Benn Schumann: Um, because I was able to kinda spend a couple of years just doing synthesis in the lab and working with amazing people there. Uh, but then, also, um, to take the molecules that I made in the lab and use them in, in biological assays. And so that's [00:06:00] something that you probably don't see very often because not everyone has the capacity to do that within the same lab, although that's becoming more and more common. Um, and so then I somehow became a jack of all trades, I think.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, and so then, in my postdoc, in the Bertozzi Lab at Stanford, I was able to kinda just use that and put this to, to use, to kinda make tools, use them in, in biochemistry. And so by that time, and also in, in the Bertozzi Lab, it was quite normal that people would make their own molecules and use them, um, in, [00:06:30] in assays, and biology, and try to understand how glycosylation works. And that's really what we're, we're carrying forward at the Francis Crick Institute. And the Crick is obviously a biomedical research institute, so, um, w- we are comfortable making the tools that we need, that we have.
We always have a, a biological question at the core of what we're doing. It would be weird if we didn't, at that, in that environment, because you can work with all these amazing biologists and clin- clinician scientists, and so on. So, um, kind of making the right [00:07:00] tools to address the right questions, I think is what we, what we want to do.
Paul Orange: And, and 'cause you mentioned tools, there's also, I think, it's on your, I got this from your like profile page on the Francis Crick website, uh, is, I know it's like a mission statement or goal, or the lab says, "We use synthetic precision tools to understand how particular carbohydrate molecules control processes in and on the living cell." And you said, you know, you're tying that back to some sort of processes taking place, or a disease state or something.
Now, I started [00:07:30] reading about this, um, I think this is fascinating. So cou- could you sort of explain some of those precision tools and also, you know, what kind of the, the, the innovation? And as you said, how some of these techniques, because you could apply them to carbohydrates, you know, why they're innovative and, and, and how they help us understand that ultimately then, either a disease process or a normal process in a cell 'cause, um, yeah, thi- this, this was the stuff that got me kinda lost in, uh, (laughs) reading up on this. (laughs)
Benn Schumann: Yeah. So [00:08:00] if you want to understand how a glycan works in a physiological process, there are several ways to analyze, uh, this. For, for example, if you want to understand if a certain, if a certain sugar structure is implicated in, you know, cancer formation or so, there are several ways to do that. Um, traditionally, using antibodies or lectins, which are carbohydrate bioproteins to kind of see if that sugar is on. And again, there's been amazing work through decades, um, in kind [00:08:30] of profiling these sugars, especially associated with cancer formation or with, um, di- different developmental stages and [inaudible 00:08:38].
Um, and there's a lot of things you can do with these techniques. Um, they are a little biased to what sequence you want to analyze because if you have an antibody recognizing certain sugars, then it will recognize that sugar and maybe a couple of others they're watching.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: If you want to come from the other, from, let's say, like, I don't know, call it a [inaudible 00:08:57] approach, where you want to understand, you know, which sugar structures [00:09:00] are found on a cancer cell versus a, uh, a benign cell, that's also possible to a certain extent. And people and techniques are certainly getting better.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: But that's a- an area where chemical tools are quite important, because you can take a sugar, um, a single sugar, which is the, the monosaccharide, which will normally enter the cell surface sugar structures when you feed it to a cell. And you can put a chemical tag on there.
And [00:09:30] that chemical tag is amenable to bioorthogonal chemistry, which is, um, a type of chemistry that allows you to unify two moieties together by a covalent bond, in the presence of, you know, a biological environment. That can be cell culture media or the cytosol or the cell isolate, or even a living organism. Um, and also these reactions are getting better and many people are developing them. And we're really kind of grateful to have the whole field [00:10:00] and pushing this forward.
Um, but, but that, that, that situation is really complimentary to these traditional binding assays with lectins and antibodies, because then you can come in a more unbiased way and profile, and kind of ask the question kind of, you know, without, without knowing from the outset what sugar structures do I find on this cell and where do I find them?
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And I think, again, like I think this is a, a huge space, which compliments other techniques. So we're working with, uh, [00:10:30] colleagues who are coming from the other side, from the more kind of traditional microbiology side and kind of see what we can benchmark our data against each other, and that's, that's been working really good. Then the one thing that it didn't do initially was profile glycan structures with great specificity. And so y- y- you get some specificity in binding through antibodies and lectins, but you don't get them from chemical tools.
But sometimes you want to have that specificity. For example, you want to y- you know [00:11:00] that if a certain glycosyl transferase is up regulated in a certain cancer, but, uh, since that's an enzyme, it's you can't easily correlate on why this is, um, with expression animals. So just knowing that it's up regulated doesn't tell you what it does, and you also can't really tell this by kind of these traditional binding assays with antibodies and lectins, because once a glycosyl transferase has acted in the biosynthesis of a protein, then all other glycosyl transferase have also acted.
So that [00:11:30] process of glycoprotein biosynthesis is kind of a black box towards many of the things we want to do. Right? So what you gotta see, you're getting the, the protein, once it's made, but you don't know, you know, which of those sometimes, you know, hundreds of glycosylation sites was introduced by the glycosyl transferase you're interested in.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, and so I think this was something that, um, again, was a black box for ages, and this was a project [00:12:00] that had started in the Bertozzi Lab in the early 2000s. So it, it was a 20-year-long effort, (laughs) um, to make chemical tools that might be specific for certain glycosyl transferases. And, um, and, again, since this was 20 years, uh, this was way before my time, right? So, uh, this is really ... this, this started at a time where people started to engineer other enzymes that kinda exist.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, for example, to accommodate selectively inhibitors or substrates, [00:12:30] and so that idea was born in the Bertozzi Lab, to make this amenable to glycosyl transferases. Um, but the, the technique wasn't, wasn't ready, or the ... we weren't ready at the time, to carry this out, because there's a couple of prerequisites that you need for such a technique to work. Um, one of them being that in order to, um, to understand the glycosyl- glycosylation structures in such detail, you need very sensitive mass spectrometers, which at the [00:13:00] time weren't really there. So only in the last, you know, five, six, seven-
Paul Orange: Mm.
Benn Schumann: ... years, we've had the capacity to really look into detail into particular glycosylation sites. The other thing is, that the approach that would be taken would be to engineer glycosyl transferase, that would normally bind a, a sugar donor-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... an activated form of, of a sugar, and look into the crystal structure of that protein and find spots, find amino acids that are in close [00:13:30] proximity to the sugar. Mutate those to smaller amino acids, that ... and that makes some room in the active site for chemical modification. And so that chemical modification can then also carry a bioorthogonal tag, so it can be transferred to the right glycoprotein, and you can trace that-
Paul Orange: Mm.
Benn Schumann: ... glycosylation. But there weren't many crystal structures, uh, on the particular family of enzymes that people were interested in. I think the first crystal structure came in 2006, um, and even then it was quite hard to understand [00:14:00] where you want to mutate. So, um, a- and there are many issues in tech- technology development, that make life easier once we went further, that chemoenzymatic synthesis of, uh, sugar donors got ... uh, became more attractive or we suddenly had CRISPR to knock off the native types of transferase
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... for example. And, and so all these developments in, in technology kind of made the, the stars align at a certain point.
Paul Orange: Mm.
Benn Schumann: Um, [00:14:30] so that we could actually kind of go after this and carry it out, not only in vitro. That was already a huge undertaking, by people who, who were in the Bertozzi Lab before me. Um, but also then in the living cell.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And this has worked so well, much better than I would have thought. Um, this might be a kind of stupid thing to say-
Paul Orange: (laughs)
Benn Schumann: ... but, um, uh, this worked so well. And now we can say, you know, "We have ... We have this tool and it works so well for a certain family of glycosyl transferase, that we can start, [00:15:00] you know, building databases and understand which glycosylation sites are introduced by which, which enzyme."
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: So then, uh, eventually correlate this with, you know, which glycosylation site might be, might be important for c- cancer formation.
Paul Orange: Mm-hmm (affirmative). And, and I think that that was one of the things that I was sort of interested in, uh, uh, uh, when I was doing some of this research, was, you know, I always ... o- on the show, one of the things is, you know, how does this relate to modern life? So I was kinda looking at one of the processes where glycosylation in, [00:15:30] in the carbohydrate structure is important. And I think the easiest question to answer is which processes aren't reliant upon that. So, I think, something that reminded, you know, in the research you kind of reminded me that your blood type is essentially determined by the glycosylation, um, on, uh, on proteins. So it's hugely important.
S- some of the sort of material said that when you get this glycosylation happening, although you can predict the residues and you know the, [00:16:00] the chemical linkage, it's not always easy to say it's this particular serine or threonine, uh, if it's a known glycan. Eh, but it's, it's, it's, uh, serine or threonine. Uh, i- is the work you're doing now getting to the point of saying, "Oh, so this enzyme will add this sugar to this, you know, this specific number residue?" Is it ... Is it helping to get, as, as you said, more of a playbook and a guide for how this all works?
Benn Schumann: Yeah. Um, I think, yes. (laughs)
Paul Orange: (laughs) Right?
Benn Schumann: The answer is [00:16:30] yes. I think that's where we want ... where we want to be at a certain point. Right?
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, you can also ask a question that's a bit more broad, basically, um, you know that these glycosyl transferase enzymes are important for certain states and how the disease ... And it's not only cancer, there are many other, um, disorders that are reliant upon-
Paul Orange: Mm.
Benn Schumann: ... the functional glycosyl transferases. Um, and knowing which glycosylation sites they introduce is great, but in, in many ways we also don't know what the [00:17:00] protein targets are. Right? Um-
Paul Orange: Oh, right.
Benn Schumann: ... so, so without even ... without even kind of going into too much detail about what's the serine or threonine, or even knowing kind of which proteins are modified by these glycosyl transferases. That's already, um, something that we don't really know, because, again, it's ... There are glycosyl transferase families, and the, the family we're interested in, the GalNAc-T glycosyl transferases, um, there are 20 different isoenzymes and, and they all act in the secretory pathway, right? So something between, you know, the protein [00:17:30] being, uh, first translated, biosynthesized in the cytosol, into the endoplasmic reticulum, and then it traffics to the secretory pathway to be secreted or end up on the cell surface.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And in that process, you know, m- many of these 20 isoenzymes, plus many other glycosyl transferase act. And what we see when we express a protein is the end result, but we-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... don't see ... we don't really see any- anything in between.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And so from the end result, it ... we [00:18:00] just ... it's just very difficult to get a trace back about which surface structure was introduced by which enzyme. And, um, and so in that respect, already knowing what the protein substrates are, even without knowing the particular serine or threonine, um, that's already a success.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And we can also go more into detail, and, um, I'm kind of putting these forward as two different aspects because they would need different, um, depths, [00:18:30] in terms of the, um, mass spec technology that we need.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And so the more detailed that you get, the more effort you have to put in to the mass spectrometry, and so, um, then it becomes a bit more challenging and you also-
Paul Orange: Mm.
Benn Schumann: ... need very capable people to analyze this data. So we're working with my colleague Stacy Malaker, who is, uh ... who has a ... her lab at Yale University, who is like a guru in, um, looking at mass spectra and understanding which sugar structure is where-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... [00:19:00] and many other things. Um, so we're working with her and she's educating us into kind of a- analyzing and validating the, the spectra we're getting through, through these mass spectrometry techniques. Because, you still need, um, people who are really competent in analyzing these spectra. It's not ... It's not, um, automated in a way that's for, for proteins alone, for example.
Paul Orange: Mm-hmm (affirmative). Mm-hmm (affirmative). And ... A- a- and, and then what is ... And what specifically then are, [00:19:30] are some of those challenges? I mean, I'm personally a little bit familiar with sort of, you know, protein identification through mass spectrometry, but probably many years ago and I'm sure things have moved on a lot.
Benn Schumann: Yeah.
Paul Orange: Um, I know, um, Elisa Fadda, who we had on this show, who I think recommended that we, we speak to you. You know, she, she spoke about some of the challenges of looking at carbohydrates and glycans compared to other biological molecules, because they're highly flexible and, and-
Benn Schumann: Mm.
Paul Orange: ... and in motion a lot more. So what are some ... what are some of those challenges that, you know, make it more difficult than say a protein [00:20:00] or, or something like that?
Benn Schumann: Yeah. So, um, multiple. Uh, when I talk to people who are not in this field, biologists in the field-
Paul Orange: Mm.
Benn Schumann: ... and I explain some of the challenges, then (laughs) which just they ... which just ask me, "Why do you ... Why ... You know, why the hell do you want to do this?" (laughs)
Paul Orange: Yeah.
Benn Schumann: But it's also intriguing because we don't much about these molecules, and so, um, part of the reason is that some of the ... of the glycoproteins, which are highly glycosylated, um, might not be very amenable to protolytic digest, so when you do ... when you have a proteome and you want to understand, you know, which proteins are in there, um, you can [inaudible 00:20:25]. For example, you would normally chop up the proteins with, um, kind of off-the-shelf proteases, trypsin is the best one-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... because it generates peptides, which have a positive charge. Um, and so b- because it keeps, um, of the license of [inaudible 00:20:25] and, um, in many of these glycoproteins especially mucins, which are high, highly glycosylated-
Paul Orange: [00:20:30] Mm-hmm (affirmative).
Benn Schumann: ... um, glycoproteins, [00:21:00] we simply don't find any licensed [inaudible 00:21:07] (laughs) in the, in the domain you're interested in, so that's-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... the very truly, uh, challenge. And then people would tend to use alternative proteases, and those tend to generate peptides, which aren't as highly charged, so-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... they don't adrenalize. And then they also have lots of glycosylation sites, um, and that makes it very difficult to see them by mass spectrometry, because they don't fly well.
Paul Orange: Mm- [00:21:30] hmm (affirmative).
Benn Schumann: Um, there has been some work by, um, a group leader who, he was a group leader in, in the [inaudible 00:21:37] when I was there, [inaudible 00:21:38], he's now in Australia. And they've done some work where they synthesized peptides and associated glycopeptides. And I think you see that once you have a glycan on the peptide, you see a drastically reduced capacity to, to ionize these and for them to, to be able to be spotted by mass spectrometry. And [00:22:00] so once you have a peptide with like four or five glycosylation sites on, it's just, it's just very difficult to see them by mass spectrometry.
Paul Orange: Hmm.
Benn Schumann: That's one of the things. And the other is then once you have these four or five glycosylation sites, they can be elaborated in different, in [inaudible 00:22:15] so they are heterogeneously about what the glycans actually are. And that dilutes the signal a lot, like, so you have, you have five glycosylation sites, each of them could be potentially, you know, any of like three or four or up to 20 different [00:22:30] structures. Um, and so that really makes it difficult, it doesn't make a, uh, homogeneous entity, which you would have on a peptide, but [inaudible 00:22:39].
Um, and so those are some of the issues we are, we are facing.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, and so that's just, it just means that there's a whole part of the proteome that we, we are not able to see by mass spectrometry, and that's a bit concerning, right, because-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... you know, there's, there's a lot of biological insight that we're basing on proteomes-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... if they, the, [00:23:00] the part of the proteome that we can't see, then, you know, we, we just really only, we don't get a complete picture at all.
Paul Orange: Right. Right. And, and that was kind of gonna be one of my questions. And I, 'cause that is something you alluded to earlier on is, we, we have these tools for studying things like DNA and proteins in particular. Um, you know, we can sequence a genome in a ridiculously short amount of time these days. Um, and as you said, we're then making connections. You know is, is the, is the glycome the [00:23:30] last frontier in truly understanding, you know, biological processes in, in their entirety, and, you know, d- do you foresee that we will get to a point where we can study the glycobiome as easily as we can the proteome or the genome?
Benn Schumann: Uh, as easily, I don't think so.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, but it makes us inventive. Like, it makes us creative in getting mutate needs work, I mean, that's a theory that once you have something that works for [00:24:00] glycobiology especially, in the context of chemical tools it also works for other types of biology. So, uh, again, I think it is a, it, it, you cannot mix the fields, a sand pit for (laughs) developing, developing tools and developing ideas and so on.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: It's probably, it will take a while, um, if at all, we will ever be able to do for glycans what we are able to do for DNA, right now. Like I'm-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... I'm not convinced that it is ever going [00:24:30] to happen. But the question is always, um, if, (laughs) there is something to be said about a field where you need innovation to drive it, because that innovation will also be useful for, for other things. Right.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, so I, I think I'm actually quite happy to have a program, something where you don't know much and you, the, the fruits are hanging very low-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... in terms of getting, um, getting new methods out. Um, we, we published a paper earlier [00:25:00] this year that, it nearly took three weeks between conception of the work to submission of the paper.
Paul Orange: Wow. (laughs)
Benn Schumann: We, we, well we basically used, we, we kind of took bits and pieces from, you know, from colleagues and collaborators, um, and had an idea about how to, um, how to, uh, increase our capacity to sequence glycopeptides by mass spectrometry. Um, and so [00:25:30] we would use chemically modified sugars, um, which is kind of on [inaudible 00:25:34].
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And instead of introducing by these bioorthogonal reactions like a fluorophore so you can see them on, on the cell surface, for example, or, uh, a biotin tag, which means that you are able to enrich for these glycopeptides, um, we would introduce a positively charged moiety, which is good for mass spectrometry in many ways-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... especially for tandem mass spectrometry, if you want to sequence this type of peptides. [00:26:00] And so we, we're not the first, um, lab to have thought about introducing a positive charge into biomolecules, not, not by a long shot. Um, but I think the combination of these chemical tools, um, introducing a bioorthogonal handle and using a positively charged tag on it, um, makes this approach quite attractive, and so, again, Stacy, uh, a friend and colleague in Yale and, and myself have thought about this, and we go, "Well, we can do this, and we [00:26:30] have, you know, um, great people in the lab, and we have great technical capacity, so let's do it," and it was literally as straightforward as synthesizing a couple of glycopeptides.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Putting on different tags, working with, um, with colleagues, with common [inaudible 00:26:47] in, um, in Bristol, who sent us the, the molecule and was all for it, it, it's, then just trying it. Um, and, and then just trying it, and it worked out really well, and so then within no time we had a paper, and so it kind of shows you that this is a field where relatively straightforward ideas can have a huge impact.
Paul Orange: Mm-hmm (affirmative). And then, and, and, because [00:27:00] we're still fairly early days, the impact of those is, is, is bigger. So something you mentioned that I was interested in as well, in the, uh, and, and I, I, I, I think the paper that I, I read, you know, one of your most recent publications, again, um, uh, just for the audience, um, if you're interested, check out Benn's, um, page on the Francis Crick, uh, website.
Um, and the whole page is listed there. There's a, there, there's a diagram of the, [00:27:30] um, of the process with these modified transferase enzymes. And there's one thing I was going to ask, and you touched on it there, is, you know, what's the range of tags that you can attach, and, and the kind of things you can use and also, and I think you mentioned fluorophores there, biotin for enrichment, and then, you know, something to give a, a positive charge in the mass spec.
Um, uh, I mean, essentially are you limited by your imagination to a certain extent? (laughs)
Benn Schumann: Yeah, I think so. I mean, um, this is a space that, it's, [00:28:00] the things that have been done are quite fractional in terms of, you know, we want to put this down, or we want to ritalize this, but really the sky's the limit, right. Um, [inaudible 00:28:10] have a paper earlier this year, or was it last year already? Um, where they have I think introduced a whole antibody through some, some of the techniques.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, like fuse it onto the cell surface. Um, so, you know, in large molecules, you can theoretically do this. Um-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... in Bertozzi lab, they have, they have made great use of [00:28:30] bioorthogonal chemistry, obviously. Um, uh, but to make, um, you know, fusion molecules between antibody and, um, and enzymes, so you can use an antibody as a [inaudible 00:28:44] target and, and also at the same time, the enzyme that's fused to the antibody to kind of, um, modify the cell surface. And that's useful, I often love chemistry although it's not, in this instance not, um, a glyco story.
But, you know, it's, it [00:29:00] is, it is a great way of unifying two moieties in a cellular background.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And so it's, I think in terms, in, for chemical biology and therefore for true developments, um, it has been one of the most transformative technologies, I think.
Paul Orange: Mm-hmm (affirmative). Mm-hmm (affirmative).
Benn Schumann: And people are, are really creative in developing new, um, bioorthogonal tools. We largely take them off the shelf to, you know, address the biological questions for interest of them.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, but, yeah, it's, it, I think it's, it's a great space [00:29:30] to be in.
Paul Orange: Yeah. Yeah. And picking up on what you just said there as well, but like the, the biological questions and you, you mentioned earlier, obviously you know, the, the, the, where you work is a very, you know, multidisciplinary institute in that respect. Um, and you've mentioned [inaudible 00:29:46] biology already. Could you maybe just give us a little bit of an insight into, you know, the, sort of the application or the, the, the processes that you're, you're looking into?
Benn Schumann: The questions we are asking are, are, and, uh, mainly in basic biology.
Paul Orange: [00:30:00] Mm-hmm (affirmative).
Benn Schumann: And so we want to understand what happens during chemogenesis for example, but also there have been other physiological processes other than cancer that have been associated with these glycosyl transferase being [inaudible 00:30:13] liquidated.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, and these, when people call [inaudible 00:30:16] disorders of glycosylation, so, you know, you have mutations, um, in one of the sites of transferases that kind of make them, kind of reduce activity, and so that leads to, um, a phenotype-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... like a [00:30:30] dysfunction in a patient. But really, I mean, there, often we don't know why this is.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, for, you know, for reasons quite difficult to understand, I'm telling you to find out, um, so people go to great lengths to study, to study these. Um, and if there is a reporter, we call this kind of reporter, chemical reporter for the activity of an enzyme. And it might be easier, um, in some ways.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, most of our time is invested in tool development, um, we are, we are kind of starting to make these, to make databases [00:31:00] where we kind of find out what the glycosylation sites are. But at the same time, we know of the limitations that we still have, right? For example, because of the still challenging mass spectrometry that I, I alluded to earlier, we do see glycosylations sites, but we, I don't think we see nearly as many as there are. Um, and so the whole process between introducing a chemical tool, which I think works very well, and the mass spec, which is also quite sensitive, I think that during that process there is a lot [00:31:30] of, a lot of steps which I think can be optimized, and again, there are lots of groups who are working, and who have, and, which is super helpful for us.
Um, and so, so then, you know, the, the question that I end up asking is, instead of seeing 10 glycopeptides, can we see 100 at some, some point 1000 maybe or so, if there are.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, and, and I think once we're there, I think then we, that what we, we can do is things with the glycosylation sites that we see already. Um, and try [00:32:00] to see if they have been found already, if they haven't, what does that mean.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, can we, you know, can we mutate and form a [inaudible 00:32:08] to, to not only to see if that has an effect on, on cellular function, for example.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And so really kind of basic biology and biochemistry to, to try to understand these processes. Um, what this should lead to at a certain point hopefully would be, you know, something like diagnostic or, if we know the activity of the glycosyl transferases, you could think about things where [00:32:30] you block interactions.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Right, so there are glycosylation sites and glycans that are recognized by, um, components of the immune system, which tend to either cancel the silence towards, um, the [inaudible 00:32:46] own immune system, so the question is, can you know where that interaction happens, can you block this? And then exclude this process or, um, make this process less likely.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, and turn on immunity against, against the cancer. [00:33:00] And so there's always, there are always applications down the road.
Paul Orange: Mm-hmm (affirmative). I, and the inter- I- it was interesting, it, it, it, I'm kind of thinking maybe this is, uh, an unfair question to ask you, but again, in my background reading, some, the disease states that kind of came up most commonly associate, you know, widely reported with, um changes in glycosylation with cancer, diabetes and Alzheimer's. And those are all diseases where now the immune system is thought to pour, failures in the immune system is part of, thought to play an increasing [00:33:30] role.
And, you know, we talked about blood type. Y- and, and the fact that a lot of these glycosylated proteins, you know, end up in the cell, so if, so they're clearly gonna play a role in, you know, identification of the cell as what it is, or, or what it isn't. So you, do you think, then, that like this immune system interaction for something like cancer, where you sort of say, you turn off that shielding, you know, could, could lead us to a state where there's a, you know, a drug you take stops an activity of a particular enzyme, and then actually [00:34:00] that doesn't in any way help the disease, but will slow the disease progression, what it actually does, that is the immune system then saying, "Okay, these cells shouldn't be here, we're gonna attack them."
You know, which is a little bit like some other cell therapies that, uh, you, you know, in development and on the market today.
Benn Schumann: Yeah, I, I think so, I think that's a fair point of you to say, um, uh, I think a, a cancer cell invests a lot of effort making itself s- you know, silent from the-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... immune system, [00:34:30] right. There are changes that have to happen on the cell surface once a, um, extreme cell being healthy and being tumor cell, otherwise it wouldn't, you know, get into the blood stream and in circulation and then form the cancer seeds. That can't happen without changes on the cell surface. And glycosylation is one of these, the fundamental changes which happen in almost all tumor cells.
Um, but these changes mean that normally that would make [00:35:00] them less cell-like, so, you know, the immune system is really good at spotting things that are, um, that look, that don't look like kind of they come from our own body. The changes in glycosylation, um, might look like that, so the cancer invests a lot of, a lot of effort into making itself silent from, um, from these, from immune attack, and glycosylation, again, plays a, a crucial part in this.
Paul Orange: Yeah. And I suppose it says, sort of like letting my mind wander off into the future, you could even, [00:35:30] you know, maybe see if you've got individuals who are at risk of cancer, you know, they could prophylactically take something to block the activity of this enzyme so that, you know, tumor cells as they arise, or precancerous cells as they arise, you know, are taken out before they get, you know, a chance to form. So, uh, this is, uh, you know, a v- a very potentially exciting avenue, isn't it?
Benn Schumann: Um, yeah, I mean, you're right. It's, it, it, you know, we, we know that these changes occur. Um, we are getting a grip on identifying, identifying [00:36:00] when they occur. Um, but the expression of these enzymes, um, this, this, as over, uh, over-expression and non-regulation of these enzymes, um, is a, might be a quick indication.
Paul Orange: Hmm.
Benn Schumann: Yeah. But for that you need a good, you need a good way to diagnose these, right, so you wouldn't, you only see over-expression in a cancer, if there's already a cancer that you can (laughs) see, right, there's already something, if you already suspect that there's, that there [00:36:30] is a structure that might be a cancer, right. So then you need to be [inaudible 00:36:35] provide circulation, for example.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And again, there are lots of people who, who developed this also for, um, the [inaudible 00:36:41] glycans, and there are NHS-approved biomarkers for, um, for certain types of cancer that are related to either very highly glycosylated proteins or glycans in cells.
Paul Orange: Well, I, so, something that I've been arguing with some of my friends is, you know, if one thing the last couple of years has shown [00:37:00] us is that if we want to and we have a diagnostic test, we can get it out to the entire general population very easily. So, you know, you could almost imagine a diagnostic test that you take every year or something if you've got a particular marker, or, you know, you just take as part of a general health check. And, you know, it, it identifies those things. But, um, yeah, I, just, sorry, I, that is absolutely a flight of fantasy about (laughs) you know, where, where this could go.
Um, so, so [00:37:30] Benn, I think one last thing that I wanted to, to, to, to ask you about was, was again, go-going a little bit more broad, so, so the work you do, and you've used the term already, it's like chemical biology. Um, in my head I have an understanding of what I think that is, but, um, what in the, in the broadest sense does that mean, and, and, and, um, you know, and, and how is it used? M- m- m- and are there other areas that you can point to that are examples [00:38:00] of the sort of the chemical biology approach?
Benn Schumann: That's a very interesting question. Um, it's also not a question that's that easy to answer, because, uh, I'm, I'm seeing this as I, in, um, sort of on comedies and, um, trying to [inaudible 00:38:16] courses in chemical biology and the question, what is chemical biology, comes up quite often.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, and there are very different ways to, to define it. Um, in the broader sense, the ba- you know, the classic use [00:38:30] has been the use of chemical tools to, uh, define, understand, uh, portray biology.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And, um, but that's quite a broad, um, I think the, the power of chemical biology is that you can titrate biology, you can associate, um, concentrations of a compound with a [inaudible 00:38:55] effect.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And that's something that's, I mean, difficult to do traditionally [00:39:00] in, in biology, right? Um, and, and I think that's again, like that's the power of chemical biology. Um, it does feed into drug discovery, obviously, because then once you [inaudible 00:39:10] things then you can look into, um, how to make a drug against it, but, um, I think chemically about it, it inherently seeks, seeks to understand.
Paul Orange: Mm-hmm (affirmative). And, and, does it, so does chemical biology inherently mean that your work you- you're doing, where you're applying your chemistry to a living organism, [00:39:30] whether in vivo or in vitro, or, or, or is it, as you say, just trying to understand or maybe alter the system?
Benn Schumann: Um, I mean I think that's probably the goal of most chemical biologists.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: But it doesn't start there, usually. Right? When you make a new tool, uh, normally, you, for example, if you make a new re-agent, the first thing you would want to see it would, if it's, what it reacts with. Like you would [00:40:00] put it in a test tube together with a couple of, um, punitive, um, reactants, and so that's quite far away from using it in the living cell yet. Um, and I'm quite a fan of thoroughly characterizing the tools one, one makes. Um, because if, there's a couple of instances where also we have seen that, you know, the, um, we thought the tool was a good one until we figured out there's a lot of stuff that happens in the cell.
And, uh, but this is only [00:40:30] possible because we have the capacities now to look for things that, you know, people weren't able to hope for 10 years ago. Um, but anyway, it does start with in vitro work. And with a test tube, and then, um, once you're quite confident with your new, um, bioorthogonal functional group, for example, does what it should in a test tube, then, um, then the next step is to take it maybe into a cell isolate and see if it kind of reacts to the proteins or so, um, what it, depending [00:41:00] on what you're, what you're interested in. In the cell isolate, if you can kind of pull out a protein you're supposed to interact with.
Uh, and then afterwards you would go, they would be introduced to the next cell, and once it works there, you, there might be an opportunity to kind of go into an organism if you have a better question to ask there. So it's, it's the whole breadth, I think. Uh, but I also wanted to say that there is a large aspect of, um, chemical biology, which is also chemical biology, which is classically been, [00:41:30] been called, um, bioorganic chemistry. (laughs) Uh, which is a little bit the other way around, right, using, making use of biology to do something that you would otherwise do in chemistry.
Paul Orange: Right.
Benn Schumann: Chemoenzymatic syntheses are a prime example. And we do that in our lab also. Um, for glycans that's actually a very, a great way to make, to make, um, sugars, then, because glycosyl transferase are being more and more well described.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, in many ways for a specialty for my concerns is that [00:42:00] you find the mammals, um, chemoenzymatic synthesi- ses are now much faster than classical chemical syntheses in, in most, in most ways.
Paul Orange: Hmm.
Benn Schumann: It's because enzymes have found a really good, you know, they, there's no need for protecting groups if you have enzymes that, that can introduce, uh, sugar structure at a particular point.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: So as the enzymes have the inherent specificity that you would otherwise get through protecting groups and through, um, serine, the [inaudible 00:42:29] of activity of a glycosylation [00:42:30] reaction. Um, and so I think that's, um, that's a huge field now, and has, has been made, it's being made through [inaudible 00:42:41] also.
Paul Orange: Mm-hmm (affirmative). Now, I, that, that's something I agree with, and that's something that, to put my company hat on for a moment, we see a lot in our customers as well, so yeah. Totally agree, using, using the biology to make useful is, you know, is, is, is only growing in importance.
Benn Schumann: Yeah, for, for glycans, though, I think where it still hits a little bit of a, um, of a [00:43:00] boundary is, um, for unusual sugars.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Like things where you haven't, where you don't have the glycosyl transferase yet. Um, and so that can be either, um, sugar structures which might be, um, artificially optimized to fit a certain mean. Like I think in the complex of vaccines I think that might be important, like to be-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... um, glycoconjugate vaccines are, you know, some of the most, actually some of the most successful, [00:43:30] um, there has been some, some confidence, right, so, um, pneumococcal vaccines, for example. Um, meningococcal vaccines. Um, are mostly glycoconjugate vaccines would conjugate, uh, a sugar to a protein to, uh, develop an immune response against that sugar. And, um, but they, you want to direct the immune response against the material of glycan. And so for that bacterial glycan is, you would often not find a suitable glycosyl transferase that, [00:44:00] uh, introduces and more kind of makes the, the right connections, although people are working on this.
So, and chemical synthesis becomes really important. Um, and also I think it's scarier, the process is scary, right, you have optimized those reactions then chemical synthesis is still unparalleled, I think.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: So I, when you want to go to a, um, to get to a point where you can make a glycoconjugate vaccine that works well against a vaccine-preventable disease, and you, and it's safe enough and you kind of want to, you know, get it [00:44:30] into clinical trials, um, and I think chemical synthesis is, is one, one of the great ways, um, forward.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Uh, and so, but also some of the sugars will be laid out towards certain, um, chemical environments or certain, you know, conjugation reactions, that's sort of when you conjugate sugar from protein.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: And so then the power of chemical synthesis to make analogs of these sugars that are not laid out towards these conditions, right, and so, and that's something [00:45:00] that, um, still enzymes sometimes struggle with. Right, so, so chemical synthesis has a legitimate (laughs) uh, right to be in, to be in the space and is, is, is greatly useful.
Paul Orange: Yeah, and, and, and, yes, and, and I think if, you know, if anybody listening is not quite sure of some of the impact this has, you know, if you think about biological drugs, so any amount of [inaudible 00:45:23] common in protein, they're glycosylating protein, so the glycosylating pattern of that finished drug is an [00:45:30] incredibly important key C step, and batches can fail because as you said, during the pr- purificational production process, it's come through a hostile environment, the, the, you know, the sugars re- don't react well to and, you know, you ended up with a, you know, potentially a completely formed functional protein, but it doesn't work as what it's intended to, because the glycosylation isn't right, y- yeah, I mean tho- those things are super important.
Benn Schumann: And that's interesting, because this is where, unexpectedly to me, m- probably not to others, this where [00:46:00] most interest comes in, comes from into glycobiology, so people who are interested in glycobiology, um, from an industrial side or from a chemical side are mostly interested in antibody glycosylation-
Paul Orange: Hmm.
Benn Schumann: ... just because of the, uh, the advent of this antibody therapies, right. Um, and, and then it's quite obvious if you think about it, the, you know, it, to me it wasn't, before this all came up, wasn't necessarily the, uh, thing. I kind of always wondered why, why so many, why there are so many people working on, [00:46:30] um, optimizing ki- kind of similar glycoengineering. So you kind of optimize a cell line like a [inaudible 00:46:37] cell line, for example, to have the right set of [inaudible 00:46:39] and transferates to make a homogenous, uh, glycosylation type. But then it's obvious if you think about it from an antibody perspective, because you want to make to or, well you want to use these cell lines to make, uh, biotherapeutics, and they have to have, um, as homogenous glycoforms as possible.
Paul Orange: Yeah. Yeah. Well, Benn, um, I'm aware of time and we've covered a lot. Is [00:47:00] there anything we didn't talk about that you wanted to mention or feel we should talk about with the audience?
Benn Schumann: I think, I mean, so one of the things that, um, I was fortunate, um, to have and I, I think it's kind of a little bit inherent to multidisciplinary science is, um, can have, you know, great support by mentors from different fields, and I think it u- unified a lot of, a lot of views from [00:47:30] all different people, and so I, I just wanted to mention that what I really found important was to, um, to have mentors from different backgrounds.
Um, obviously there's definitely [inaudible 00:47:43] to being a supervisor so without, um, Peter Seeberger and, uh, Karen Bertuzzi, uh, I, I don't think, I don't think we would be doing the science that we can [inaudible 00:47:55] be able to kind of, you know, appreciate what's new and what's missing in, [00:48:00] in, in the field, and also kind of carry out science in the way we do, right?
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: Um, being, being motivated to seek for, for, for whatever has, has [inaudible 00:48:11] and, and ask the right questions. Um, but also to kind of give that forward for the next generation. Right, so, uh, I think we try to model on that after, um, you know, all the positive things that I've experienced in my, uh, in my career so far and, and so I think, I just wanted to mention that I think [00:48:30] this is a very important [inaudible 00:48:33] forward.
And, um, you know, being, being, uh, recognized as a team was one of these things where we, we won an RC award this year, which was an award basically to the whole team that, um, contributed to making these chemical precision tools work, and so that includes, I don't know, 50 different people who were all part of making this work, so, um, I think this is multidisciplinarity as it should be.
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: [00:49:00] Um, you know, very positive situation, very positive experience, with, with views from all kinds of different, uh, different people, um, with different backgrounds.
Paul Orange: Hmm. It's interesting you mention that, Benn, because I have another interview with recorded, which we haven't put live yet, um, uh, with, uh, Monica Perez-Temprano, and, uh, she, again, felt very strongly that, you know, one of the key duties is to pass on good mentoring. Um, [00:49:30] and, and to get that skill within the people and to make those connections. Um, so yeah, I, and I agree completely with, with both, (laughs) both you and Monica on that one. Yeah, absolutely.
Benn Schumann: Yeah.
Paul Orange: Benn, um, if people want to check out your research or look you up, where is the best place for them to make a start?
Benn Schumann: Uh, I think our website is a good place to start. Um, so [inaudible 00:49:53] you can just Google my name and [inaudible 00:49:57] and it should come up.
Paul Orange: Yeah, and, uh, we'll put a link in the show notes as well, [00:50:00] but I, yeah, concur, you can just google Benn's name and it will come up. (laughs)
Benn Schumann: Yeah, I, I think the, the RC are also producing kind of a media package from their horizon board. Um-
Paul Orange: Mm-hmm (affirmative).
Benn Schumann: ... so that's I think going to be a summary for, um, people who might not be too familiar with the, with the type of research, so, um, so I think that's going to be great, I've seen some of the material, I sent, I sent out some of the material and I've seen some, you know, drafts and, uh, it will be good, but it's not up yet, but soon.
Paul Orange: Okay. Well, congratulations on the award and I don't think, uh, I don't think we can, can't wait to [00:50:30] see it. Um, and I would say to anybody who's been listening, if, if you're totally interested, I would check out, um, Benn's website, there's lots of interesting links. But, you know, give yourself an afternoon, 'cause you will sort of fall into, uh, clicking one thing after another. Um, Benn-
Benn Schumann: It, it, it's a nice rabbit hole to fall into.
Paul Orange: Yeah, uh, yeah, it certainly is. I, I agree. I've got pages of notes in front of me. And, um, I think we, we skimmed over a, a very small amount. Uh, Benn, um, firstly I want to thank you very much for your time this morning. [00:51:00] Um, and it has been a fascinating, uh, discussion. Um, you know, one of the privileges I get from doing this job is just to meet, you know, really clever people doing really amazing things. Um, and, uh, you've kept the track record going, it's, uh, it's a real privilege from my side, and thank you for your time.
Benn Schumann: Thank you so much for the invitation, it was a lovely discussion.
Paul Orange: Once again, I really want to thank Benn for the time he took to talk to me. Uh, Benn and I spoke towards the end of September 2021, [00:51:30] and you'll know that Benn mentioned an award towards the end of our discussion, so by the time you listen to this, there may be more details out about that. Once again, I would really strongly recommend you check out Benn's website, and have a look at some of the publications if you're interested in understanding some of the tools and approaches he uses in his research. I
think this will likely be our last episode of 2021, so I guess it really only remains for me [00:52:00] to wish you all a very happy festive season if you celebrate. Um, and if you don't, I hope you have a good winter period anyway. And I hope that we'll be back in 2022 with more interesting interviews and fascinating insights into how chemistry affects and impacts the modern world around us. So until we speak again, stay safe and stay well, and I'll catch you next time on The Modern Chemistry Podcast.
[00:52:30] Thanks for listening to the Modern Chemistry Podcast. Our theme music is provided by Kevin McClout under Crete Commons license. And if you subscribe to the show, you'll have the next episode dropped straight into your podcast feed.