Richard Jacobs: Hello. This is Richard Jacobs with the future tech and future tech health podcast and I have Dr. Richard McCulloch, newly minted professor at the University of Glasgow. So Rich, thanks for coming. How are you doing?

Dr. Richard McCulloch: I am very well. Thank you very much for inviting me to your podcast. It’s a pleasure to speak to you.

Richard Jacobs: Yeah. So tell me about your research, what are you working on?

Dr. Richard McCulloch: So, so the, did we say this thing is out of my lab is in Tracy, then the biology of the genome of Samson organisms. So you know, the repository of all the information is needed to generate proteins in RNA and so forth. That drives cell function as particular what would in Tracy then, is trying to understand how that genetic material is protected from harm and how it’s transmitted in the process of cell division. So I was copied and moved from cell to cell. Yes, that’s a pretty wide field that we work in. I guess most people reduced the study, they send in human cells because that’s what makes us up. But what makes us maybe a little bit definitely was initially we then we choose to study these processes knowing human cells, but in parasites that infect humans and causes disease in humans. Eh, we’ve chosen to focus really on two different trypanosomes parasites. One of them is called the trypanosomes, mainly found in Africa and it causes disease in humans called sleeping sickness. And the other parasite, another single-cell UK, which is called Leishmania. And that causes a very different disease. But in fact, it causes a number of different diseases and it’s got much more weight spread, a worldwide distribution than trypanosomes.

Richard Jacobs: What are, what are the vectors and mechanisms of action of a parasite? Does it actually integrate with their DNA or does it keep its own over cellular machinery like a virus? And what are the mechanisms of action as a parasite?

Dr. Richard McCulloch: So that’s a good question. So one reason that we’re interested in these two different parasites is quite different mechanisms of action. So the common feature of these two parasites is that the infect humans both through the bite of a blood peering insect. So in the case of trypanosomes, is it Testy fly and the case of Leishmania in the sand fly, both of them then go into the bloodstream, but then they do something really very different from each other. So trypanosomes they live just in the bloodstream. So they don’t infect any of ourselves at all. They just live in the bloodstream and they have to survive and there, and they’ve got a real problem with that because when they’re in the bloodstream, they’re not confronted by our immune response to them all the time. So they have to come up with a strategy to try and cope with that constantly immune barrage from us. Leishmania does something very different. What they do is they infect ourselves. So they go into ourselves and they live inside the cells and that means they have to be transmitted from cell to cell. One reason they do that is that provides them a means to somewhat hide from the immune system rather than being constantly exposed to them. So the fact that these parasites do things similar in the sense that they’re both transmitted by flies, but once they are in us, they do different things, allows us to do comparisons about how, how the parasites operate and how they compare with each other.

Richard Jacobs: Is the goal of parasites permanent residents by the host or is it to just either long enough that it can, you know, lay eggs or whatever it is and have that light seed off the organism and then leave?

Dr. Richard McCulloch: Again a good question. So these are both of these parasites so could have been chasing for us because they just single cells so they don’t make eggs. I mean like that they don’t have complicated developmental biology like a, I don’t know, something like hey warms or something like that. You may imagine. Um, but the goal is just as you say, so the really as far as we gonna understand the goal once they’re in a host is to, is to live and prosper on that host for as long as it takes them to be transmitted onto another host. And both these cases. What that almost certainly means is be able to survive a in the host long enough that when another fly comes along and fits in that host, it then takes up the parasite and it can, it gets passed on to another host. So, the parasites because they’re completely relying on us or their animals and for the survival. So their growth needs us. Your feelings from us for instance and as a result of that do cause severe disease and they can potentially cause death, but it’s a byproduct of the transmission biology.

Richard Jacobs: What was the goal? Like the suits you fly you fly is not deliberately and veganism and parasite. The parasite just happens to use the fly as a host and then there’s a fly will land on us. It’ll go into us or is it.

Dr. Richard McCulloch: Yup, that’s exactly right. So we often talk about, to give you another example of this kind of palace Ethology, I get more people out of malaria added that’s transmitted bay, transmitted by mosquitoes and people will often see that mosquitoes are the biggest, one of the biggest causes of disease. The reality is not the mosquitoes is doing that is the fact that they, some of them happen to carry a plasmodium which causes malaria disease and it’s exactly the same indication of trypanosomes or Leishmania. So the taxi flies are, or the sand flies in the case of Leishmania, what they are is just a vehicle that has been exploited by the parasite so that it can move from mammal to mammal. And a question that often comes up in the field is just what is the evolutionary history way back in the past, did they stopped as parasites or flies or did you start over with parasites as mammals, friends. And how did the two of these things get linked up? It looks as though the evidence is that they probably started in flies, but it does not absolutely say up.

Richard Jacobs: I was just thinking about malaria and was there any way tried to make mosquitoes resistant to malaria so they can’t be carriers of it. It seems like all the focus is making people, you know, resistant to malaria or you know, killing all the mosquitoes, but what about making the common carriers of this stuff not compatible?

Dr. Richard McCulloch: Yes, that’s exactly. Those kinds of fakes experiments, it’s really probably two smaller one for those kinds of projects are being attempted now. So people are attempting to genetically modify mosquitoes, for instance, to try and come up with strategies. That means that if for instance, they might not be able to pick up the malaria parasite or when they take up, it might not be able to go through the complex developmental program, its veins with within the fly. And as you say that that would, if that could work, that could potentially be a very, a very productive way of trying to, to prevent the transmission of any of these parasites at all. The same kind of work is not anywhere near as advanced and that’s partly because of the diseased part of malaria is a much bigger disease. It’s also because we probably have a better understanding of the biology, genetics, and ecology of mosquitoes than we do off of taxi flies or sand flies. But probably in years to come that that will come. Yeah.

Richard Jacobs: So what are the mechanisms by which these two parasites go into us and why don’t we create a unit to get rid of them?

Dr. Richard McCulloch: Okay, so that’s really, they connect the release that actually that I interested in in this area. And you’re absolutely right. You would imagine that we’ve got an incredibly sophisticated system for immunity. We were very, very good at fate and often factions. So you know, the important question then is how is it that any parasite is able to get into the host or is it able to, to grow? And in the case of trypanosomes, It is able to grow in the bloodstream where it’s constantly exposed to the immune system. How can they grow in these environments and not be cleared really rapidly? It turns out that the user really put the face of is really quite a simple approach. But the underlying biology that drives us is really rather complex. So in essence what trypanosomes do is that the Schroeder surface of a cell and one very dense was called a coat of a protein and the proteins called surface glycoprotein. But the name’s not important. It’s just a protein that forms a kind of protective layer around the hall of the cell. And it does that in order that basically becomes the only protein that we as the infected host can see. So all the other proteins that you actually have to get at the top of every cell to make a cell function, you know, to take up nutrients and so forth, they’re not seen. Instead, the only thing that we see is this variant surface glycoprotein, this surface coat. And that alone means that it has a short term capacity to survive. Because when we generate antibodies, we only generate antibodies against our immune reaction, against the BSG and not the other proteins. Of course, the problem is that we do generate an immune reaction against the surface coat ‘The DSG’ and what that means is they have to come up with a means to constantly change this. And in essence, what they’re doing by doing this is that just running away from over for a motor immune reaction. So what the parasite, the trypanosomes do is periodical, it goes from inflation one surface to another and then another and then another and another, and it just keeps moving forward. Which means that as the host, where we start to get, it takes a few days from immune reaction to form against a particular surface coat. There’s a need and because they’re able to change the expression to another surface coat, that provides them with a short window where they can, they can survive. And what this seems to be manifest in their faces is that you get and trypanosomes go into the host, they grow up and you can mean to see the number of parasites grow and then there’ll be an immune reaction against them and the numbers will drop. But then because they’ve changed from one type of VSG, one type of surface coat to another, you’ve got another increase in trypanosomes and then another drop as he had been reacting to then. And then you outgrew us and it goes on and on and on. The only final thing I was going to say is that it seems to be so successful, their strategy that they’re capable of sustaining affections for years and years. And in fact, it looks as though very similar strategies are used in lots and lots of different ordinance rebate and so forth.

Richard Jacobs: That’s what was interesting is there has to be good communication between the individual cells of the parasite. Because let’s say there’s a hundred of them and they have, you know, protein code A, how do they know it all switched to B and then as there’s a million of them, I would think they all upgrades or the new coaching code. Have you observed about how fast they do it and do they do in concert and how do they orchestrate this, division of immunity once they get to large numbers?

Dr. Richard McCulloch: Okay, that’s a great question and that is what I’ve described to you is the, I can a simplified version of how this works. You’re absolutely right. In principle, what they’re doing is they going from expressing surface coat A to surface coat B to surface coat C, D and so forth and you’re absolutely right. If that was the case, what you would imagine that doing is the communicating with each other as some way to see, okay, no, we need to switch from this surface coat to another or alternatively monitoring something about the host to see here is the immune reaction. No beginning to kick in and we then have to make the switch. One of the big surprises over the years that we’ve been studying this is that seems to be not that sophisticated level of coordination at all. What they do as far as we can tell is that they make any changes in gene and surface coat expression just all the time just they do it caustically and randomly all the time. So they don’t actually listen to the immune reaction of the host in order to respond and change coat. They just do it themselves and equally, they don’t necessarily see them. I’m no expressing VSG A and I’m going to express VSG B. Once they begin that process it can move and you know, lots of different directions. One cell moves to B another to C another to D, and it becomes an incredibly complex mixture of surface coats that are expressed. So it’s a much less tidy process than you might imagine. There’s one, there’s one complexity to add to that it’s not the case that the parasites don’t communicate with each other at all. They absolutely do. So there’s very, very nice work by mainly by a colleague Aden Raba, a number of people that show that actually, the trypanosomes do normally reach high density, high density in if infection. And what they do in those cases is the actual turnoff replication of the cells. They do that, in fact, to try and prepare themselves to be taken up by tipsy flights. But that almost certainly, and we don’t, we don’t have tall understand this, but almost certainly influences the way this coat switching operates or it certainly provides another perspective on it. It should be a summary of what we’re saying. It should be a nice simple audit process. But in fact, it’s remarkably complicated. The process and with any generates an enormous amount of diversity in the cells and populations.

Richard Jacobs: So when you look at someone that’s infected, what is the population of various protein coats look like over time? Have you studied that? You know you have 100% A, we’ll just start out with like 95% A and 5% B and then once it develops to a certain point it’s you know, 12% of A, 18% of B, 13% of C. So what does that look like?

Dr. Richard McCulloch: So a lot of experiments that we do to analyze this is using modified trypanosomes. So we’ll make muted sprints and particular genes and that ended in a culture dish. We can grow them where we can ask, okay, we know at this point when we made these mutants expressing the SGE, how frequently do the change to another VSG and what type of VSG did he change to what we realize in the last probably five or six years, and this is from a number of difficulties around the world, is that kind of experiment in the lab doesn’t really capture the full complexity of what’s going on. So a number of today in a set of experiments would be done recently where people set up or followed the course of infections and what they dealt was the sophisticated sequence and approaches to capture the VSD genes that are being expressed at what seems to happen is exactly what you’re saying. So what they’ll do is you put in a small number of trypanosomes, to begin with, and then as you follow the course of innovation quite rapidly, you get a really diverse collection of different dsg’s being expressed. And that diversity seems to be maintained right throughout the course of an infection. And now what we don’t really understand this is where we’re alluding to and then the experiments do know is what is the, is that an all done in there? So there’s when one cell expresses one VSG does that individually lead to another VSG and so forth. And is it just, is the complexity in there because of a population dynamics. So those, those were the order within a single cell. But there’s much bigger complexity in a population and these are difficult experiments to do as you might imagine.

Richard Jacobs: Well, let’s say to, at a certain point, it’s got to be communication. It was thinking about certain points. The RSA now has to say, all right, we need to make this host excrete something or, or express some things to that. The outside world knows we’re here and we’ll take us up so we can move on. So there’s got to be that happening too. And at what point does that happen? And just as the expression profile changes of the parasite.

Dr. Richard McCulloch: So that’s a very perceptive point you make and that we don’t do understand how that works. So the parasites definitely do a secrete signal that causes this change that was described in between rapidly replicated in cells and non-replicating the cells. So we, a lot of work from a number of different labs have begun to, what they do is the symptom to secrete their signal. Um, and when you get lots and lots of parasites, you inevitably build up more and more of the signal just by, by density. And as, when that happens, it triggers, it reaches a threshold and it triggers a change in the behavior of the trypanosomes, so what they do is they take that signal, they take it into the, into the trypanosomes and that leads to a cascade of gene expression changes that changes their whole biology. It changes their morphology as well. The metabolism, Eh, the DNA replication that the question you ask is, is absolutely correct. What we’re now trying to understand is how does that link to the process of PSG coat switching or which was called entertaining mediation. Um, and at this stage, we don’t have a really clear answer to that. Most of the time when we do the experiments, what we’re doing is we’re doing experiments and actually fairly artificial sales that replicate, they are just machines for replication. And they don’t, they have lost the ability to secrete or recognize their signal. Part of the reason for that is because we’re fairly sure that the process of replication of genome replication is intimately tied and Genovese, um, BSG code-switching. But the fact that you actually have this added behavior of secreting the signal, responding the signal and changing their behavior, it leads us to believe there must be a link to antigenic variation, but we don’t exactly know yet what that link is and how it might be manifest or, or how the gene expression changes that may occur. Or like Dakota is, is where we’re leading to in, in studies of a woman. But we haven’t quite reached that stage yet.

Richard Jacobs: I think, just pure opinion on my part. I think it’s better to assume that the parasites, the individual cells are far smarter than we can imagine and needs to monitor the host. I’m thinking about it. It needs to monitor the host to see how sick it is. There’s some point they’re going to be in trouble. They need to modify the host somehow so that again, the host will give up a signal that they’re there, they can be taken up by someone else. They need to know how many of them there are. They need to know the portfolio of expression of the, you know, the coats, the immune system invasion, how that’s going. I mean it sounds like to me there has to be tremendous communication on many levels going on for this to be a successful endeavor. They have to monitor a lot of things.

Dr. Richard McCulloch: So what you’re saying is fundamentally correct of course. It really wouldn’t necessarily be to the better for benefit of the parasite to grow so rapidly that the reach a really high density in the host and that consumed all the nutrients that we have in our blood for instance, and overwhelms the host and kills them. Because what that means is that the limit, the ability, to transmit and, you know, we don’t exactly understand, transmit to another host through the testy fly and we don’t, we don’t really know what the timeframe of that is. Of course, the longer you can sustain in this direction, the bigger the chance you have to be taken up by another testy fly. That feeds us on a host. So obviously, certainly what we were just talking about, the density signaling mechanism is probably part of that is probably a means to cap the level, the intensity of the infection to try and, you know, limit the possibility of killing the host. But it’s Kind of messy, this process because we know, the other things are going on here. So the, so, well, I’ve given you an impression up to know is that trypanosomes live Just in the bloodstream or arteries and beans. And actually, we now know that’s not true. There’s been recent work, this begun to explore where you can, you can find trypanosomes in an infected individual. And what we can see is that the parasites move into tissues in the host. So the move into adipose tissue, which is fat tissue, they move into the skin and in some organisms they, they move into the reproductive organs. And there’s evidence that in those circumstances, the behavior, their morphology, the gene expression, and the metabolism changes, and that may be a component of exactly what you’ve been describing. It may be what they’re doing there is trying to limit the potential of the overwhelmed host.

So the move into these tissues that can provide them with maybe a respite from the immune response. Maybe it provides the host with a respite from the infection, but maybe also pervade a little pool of an orphan affected parasite Terrain Zone that can speak back into the host. Now, this isn’t probably perfect though because one of the reasons the disease is called sleeping sickness is because such a partisan is not only go into the skin and fat tissue. And so of course what they also do it late quite only on infections is the cross what’s called the blood-brain barrier. And they go into the central nervous system and it’s at that point that the main symptoms of the disease are manifest, which are urological disorders. What we’re beginning to learn in the last few years is that the idea that there are simple replicated machines and the blood is really not true though. This disseminates more widely in the host. And that may relate to exactly what you’ve been saying, Richard, that the, they’re trying to modify the biology to maintain infections and maintain the host maybe.

Richard Jacobs: The question is the, how much variation has been observed, any like of her genes for instance. Is it endless variation? Does it follow a pathway that is followed over and over again? Therefore it’s predictive. What have you seen there?

Dr. Richard McCulloch: So there is quite old data that suggests that there’s a, a kind of a pattern of the way set and tapes of, of the issues, are expressed. So we know that some classes of VSG’s are found relatively early infections and some classes of the VSG’s are found slightly later infections and then another class of the VSG of bone late on an in the face. I’m saying classes of VSG’s because there’s not very specific VSG’s or we don’t exactly know everything about the, what makes these classes. The one thing that we’ve, that we’ve learned about how this may operate is, and this comes back to what you just said about is that endless variation is that the, one of the things they do very lean infections is they begin to generate what looks like completely new VSG’s that we don’t normally see if we go searching in digital. So let me tell you, explain this a little bit more so, in any genome, what we tend to think of as is genes are there to generate products that are immediately active and do things like the, they make a structural protein or they catalyze an enzymatic action. In any genome, there’s quite a lot. There are a few genes within the genome that we call pseudogenes, and these are genes that at some point or other we’re functional that could generate a product as functional. But the subtle mutations, that means that they lose activity and they can generate the wind protein. It turns out the, what trypanosomes have done have they filled their genome with VSG pseudogenes and what we know is that, that that term pseudogenes in the context of trypanosomes is actually accurate, because pseudogenes would suggest they do nothing, that they are just as remnants of active genes. Actually what trypanosomes do with the pseudogenes is they are a prime source of these completely novel VSG coats that are made. So what they seem to be able to do is he seem to be able to take little parts of all these genes that can be sued. Those, they’re often pseudogenes and they can splice them together and really complex patterns to generate VSG’s that really at the start of an infection where they are in the genome at all. But by the end of the infection, they are there. And the scale of this is truly remarkable. So trypanosomes have got, we don’t know the exact number, but it’s those ones of these genes, it’s across the whole genome is maybe 20% of all the genes that it contains in its genome. And because it looks as though they can be the events display some together. We began to think that the capacity for UVSG’s is virtually limitless. We’re not absolutely sure that because quantify these things is really hard obviously, but it looks potentially that there’s a huge, nearly endless capacity to make a UVSG’s Jesus and there’s a parallel to be drawn there between what the trypanosomes do and how we as the host face the eviction. So I’m sure yourself and lots of your listeners know that what we do is our immune system is generated in the course of development and what we do in the course of that development is we take genes that make the important antibodies for instance, or the receptors for the immune cells and we rearrange them and we build them up into thousands and thousands of novel genes and that the mechanisms that underlie that and VSG switching are very, very different. But the principles may well be the same. That what you need to do, what we need to do to tackle invasions is have a really sophisticated armory of immune reactive molecules. And what the trypanosomes have to do to counter that has a really wide armory of these surface coats. Trying to quantify this and trying to quantify the SD switching and trying to quantify the numbers in these is what we’re aiming to do now. But it’s a big challenge. A big challenge.

Richard Jacobs: How many different types of animals and creatures, for instance, can simply get infect and have you compared the expression of the different protein coats in various animals to see if I can certain ones, you know, there are a certain pattern and other ones with other patterns or even amongst humans.

Dr. Richard McCulloch: Okay, so that, so that’s actually, what you’re asking there is really a key question in how the process of antigenic variation operates. Because what I’ve really been talking about here, is infect, one species of trypanosomes is cold trypanosomes aprecia and most of our knowledge of how this work is derived through study of trypanosomes aprecia. And in part that’s because it was one of the first trypanosomes species that was phoned and it was the faster was able to be cultured in the lab. It was the faster we could genetically manipulate. So it became, they can have what course bio, we do things. Actually, trypanosomes, in fact, lots of different species and with trypanosomes aprecia, some species are large, it’s like humans. There’s a number of other species of trypanosomes that really don’t infect humans. They totally affect animals. Are we it, till a few years ago, I think we were convinced that older lessons that we, that we would land in trypanosomes, would be easily converted to the two other species, which are very closely in evolutionary sense of a close, but experiments now being done just secrets in the genome of these parasites trying to catalog all the VSG’s that are in them and experiments that are beginning to initiate now are beginning to suggest those it might not be the same at all. They may use antigenic variation despite the fact they all have VSG’s. The catalog of VSG’s that they have is different and the some evidence that the way that they rearrange those VSGs is very different. So we may have fallen into a slight trap and thinking about exactly how things work in trypanosomes and imagining this is absolutely the key spot for other trypanosomes that are similar to it. So we need to be careful. We need to test a lot of the things that we did in trypanosomes. We now have to revisit and use all those species to try and really understand the underlying.

Richard Jacobs: Why can’t you inoculate? Why can’t you get a population of, you know, these parasites that have expressed 500 different proteins, you know, kill them but you know, you still have the proteins intact and inject with someone whether they’re infected or not infected, you know, maybe it’s someone that’s recently infected. You can do later stage population that’s been killed and inject that into them to inform the body to stop it or vice versa.

Dr. Richard McCulloch: So one of the reasons people regularly say that you can’t generate vaccines against a trypanosome is because of the system of antennae radiation and that’s because if they can be it is that what you would want to do for a vaccine is immunize them with a protein, this bake cell. So that when they, when they are confronted by any different trypanosomes that capable of recognizing that because that protein antigen is really similar between the different trypanosomes. The thinking behind that is a problem is that the VSG coat prevents recognition of though is much more conserved antigens. So the question you’re asking is an interesting one. So could you actually, could you actually simply understand the entire repertoire of VSG’s that are ever possible be made and generate a cocktail. That captures all of that. And so trypanosomes which we are talking about and I think the answer to that is probably no. And the reason is what I’ve just described of capable is, seems of virtually limitless rearrangement of these genes so that they can generate very, very novel VSG’s that however hard you try to generate a collection of 500 or a thousand different VSG’s as a source of immunization, they are still able to generate new ones. But the other trypanosomes species, I think at this stage, we don’t quite know that if they use a much more limited repertoire of genes or they’re not capable of these really complex rearrangements, maybe then there is the potential to do that. But no one is brave enough to try that kind of experiment yet at all.

Richard Jacobs: I’m trying to think of what I was going to ask you here.

Dr. Richard McCulloch: No problem.

Richard Jacobs: Not everyone dies of this infection, right? I mean, there are people that build-up or what happens? What have we learned about studying people that survive this? What do women do? I mean, it’s just them doing to eventually get rid of the parasite or does it just go into like a, a dormant state forever and still stay resident with them? Like what are we learning from there?

Dr. Richard McCulloch: Well, it is fine in virtually all cases of a human being infected by a trypanosome if you don’t intervene a toll it will be lethal. So most of the studies suggest that once a person’s infected, um, if you don’t provide drugs to try and clear that infection, they will ultimately die. There is a small number of cases where there have been reports of people who’ve been infected and then through long-term monitoring, they don’t seem to have trypanosomes whether that means that they really have successfully managed to completely fight off the infection and they’re absolutely clear on they never get infected again. Or whether the trypanosomes are just are present in those individuals, we’ve not been able to detect them. And the disease may reoccur much later on. I think we don’t know. And the reason for that is because the infection can last such a prolonged period of time, but the basis of people dying or animals dying of trypanosomes basis is not really to do with really long term infections, is actually to do with movement of the trypanosomes from the blood into the central nervous system and when it gets into the central nervous system its effects, urological effects or source of ear. That’s the cause of disease. It’s actually not, if you only lived in the blood, probably, people could, they wouldn’t be, they would be ill but they could live for a really prolonged period of time with it. There are so few cases of people that, that we know have been in infection and apparently clear that it’s very difficult to try and understand what may or may not happen in those individuals.

Richard Jacobs: Just a couple more questions on this. Where do you think the breakthroughs is gonna come, you know, I know, you know, if you knew you, you’d be further along. What do you, what are your guesses? What do you, what are two or three promising leads that you’re following up on where you think of breakthroughs will come and what will that breakthrough be?

Dr. Richard McCulloch: So I think one of the real, one of the reality in this area of, the way that the trypanosomes effects and the dynamics of the patient and the transmission, what we were talking about as regards the communication between them, where they changed from replicated to non-replicated forms. I suspect that has real promise and thinking about trying to intervene in the disease because that’s likely to be a quite specific process, a process that’s evolved specifically. And the pattern says that means if you could really understand it and you can, you can interrupt it. You could probably block the prolongation of the infection. You could probably cure somebody with that. So we sort of understand how the rearrangement reactions that go on, they’re called between VSG is a course. So we, we sort of understand the machinery, the cellular machinery that drives those reactions or catalyzes those reactions. And the sad thing about those that machinery is it looks like its fake sailed with oozy, looks as always just a general system from the maintenance of genomes. So what we are now beginning to trying to understand is other, is there something very head of the reaction, the very top of the reaction that specific, so how do we actually stop the process of changing from one VSG to another? What I see is that it’s not just my lab, there is a number of other labs that are doing this that are in this case that are some potentially promising leaps. So recent studies are found, what looks like a very novel, a factor that seems to interact with the site that the VSG gene is being expressed in a modulated activity. And that looks really, we don’t know much about it, but it looks very specific to trypanosomes or trypanosomes related organisms. So that could be a good lead. And what we’ve been trying to do is trying to characterize the actual genome damage veins that might start this whole process of rearrangement and in that case, we’ll get into, get some leads about structures that form where the VSG is being expressed. That again, if we could really understand what those structures are, what the bones by and how the tendon to the rearrangements, again, that might be a lead burden in the intervention. But as we said at this stage, these are kind of basic fundamental science questions, but not quite at the stage of translation and to drugs. Although with luck that could be possible.

Richard Jacobs: Well, very good. So what’s the best way for people to find out more once to get in touch with the lab or you?

Dr. Richard McCulloch: People are very welcome to ask questions on Twitter. So the lab has got a Twitter page that we were more than happy to interact with. Hey, we’ve also got a lab website and my lab is part of a bigger consulting of parasitologists in the university of Glasgow, some of whom are in, what’s called a Welcome Center for Integrative Parasitology. And that’s got a website where they’d be absolutely more than welcome to email through that to the administrative staff. And then they’ll disseminate any questions that they’ve got about Parasitology to myself or any of my colleagues.

Richard Jacobs: As you should do an unwelcomed center from Parasitology as parasites are never welcomed.

Dr. Richard McCulloch: That’s very true. Very true.

Richard Jacobs: Well, very good Rich, thanks for coming on the podcast. I appreciate it.

Dr. Richard McCulloch: Okay. Thank you very much. It has been nice to talk to you.