[00:00:00] Hi everybody. And welcome to this week's podcast. This week. We're going to talk about. Ticks. It's a story we covered when we talked about alpha gal syndrome, but it's amazing the number of tick-borne illnesses that can actually occur both in humans and in animals, other animals non-human animals, but how do we deal with the problems of ticks and are they growing and seems like they really are.
And are there new technologies that can help us strategically control tick-borne illness? [00:00:30] By modern biotechnological means. And today we're speaking with Dr. Monica galinas, she's an assistant professor of biochemistry and molecular biology at the university of Nevada Reno and Dr. Jason Raskin. He's a professor of entomology and disease epidemiology at Penn state university.
So welcome to the podcast, Jason and Monica. Thank you for having us. Thank you. Yeah, this is really cool. I think that that's such a universe that I've never bothered to really [00:01:00] look at. And, uh, but ticks are always there, especially where I live out on a farm. We'd see them almost all the time. And as disease vectors kind of fly under the radar next to mosquitoes.
And so, but still very important in terms of human pathology. So we think of these as kind of, you know, occasional pests. You see one now and then on your. And you or your pet, but how much threat ticks pose in terms of disease vectoring? So, one thing I would say is [00:01:30] that your viewpoint is a little bit colored by where you are.
I'm here in central Pennsylvania. I've ticks are a major public health.  there are ticks are actually tick-borne diseases are actually the most important vector-borne diseases in the United States and, uh, central Pennsylvania, especially central Pennsylvania, where I'm located is essentially ground zero for tick-borne diseases.
So here in state college, People are extremely aware of ticks [00:02:00] and tick borne pathogens, primarily,  Lyme disease, uh, parasites. and that's going to change depending on where you are in the country. So that's really important. What are some of the diseases that are commonly vectored and you mentioned Lyme disease, but is that the big one or are there more.
, there are more, uh, definitely there is a, especially again here in, in sort of the Northeast there's Polaski and virus, and also a very, very closely related virus called deer tick virus, which are in the tech tick, born in [00:02:30] cephalitis group of viruses. They're much less common compared to Lyme disease, but they're, um, much more than.
So they can still be very important and case cases seem to be on the rise in recent years, uh, and ticks can also transmit Anaplasma and Ehrlichia and other types of tick-borne bacteria. And just to add to what Jason said there. Almost about 20 different pathogens have been identified so far. [00:03:00] And, um, there, there will be more as we learn more about different diseases, so many and even one tick species say for example, so this scapularis that is known Lyme disease.
Vector can transmit up to seven different pathogens, including post. That's really an interesting point because it seems to me that you never heard of ticks transmitting disease. You know, at least I didn't, uh, you know, 20, 30 years ago. And then you started to hear of Lyme disease and then you would hear [00:03:30] about something else, maybe alpha gal or something, which you know, is more of an allergy than a, than a, , than a disease.
But are we getting better at identifying the diseases or have they always been here, but we've just missed. , I think it's a mix of both. We have better diagnostic tools now, and also the, uh, that's why probably be at the know a lot more about these,  these pathogens. And also if I'm not mistaken, Lyme disease [00:04:00] was identified in 80.
So it's not really that long. We have known about Lyme disease. We knew there was something going on in Lyme Connecticut and other areas in the Northeast, but we just didn't know the pathogen and the vector. So now, since we know, , and the ticks have been getting a bit more of a lot more people doing research on ticks.
So I think, , that's how we know a little bit more, um, diagnostics of course. Plays a big role [00:04:30] up until I remember five years ago, um, CDC used to only report 30,000 cases annually of Lyme disease, or at least that's what the CDC website suggested. Now we know that this is the number is close to half a million.
One of the things that's important to realize is even though that Lyme disease was only sort of described and recognized in the 1980s, uh, it's actually been around for a long, long time. People have gone in and, and tested museum specimens and mummies and things, [00:05:00] uh, for the Lyme disease parasite, and they found it.
So it's been around for probably hundreds of years. Um, if not longer, so how serious are tick-borne illnesses? I know most people see a tick, they pick it off and throw it away. And don't think twice about diseases that may be vectoring. People are getting more aware now. And, um, since I know that we, the same foot got to fix that.
Uh, here in Nevada, there aren't very many texts, but we do get samples from people in [00:05:30] Nevada. They have been to California site and got a chicks and they usually send us, takes a, B. People are definitely getting more aware of different diseases. How prevalent they are. As I mentioned, almost about half a million of Lyme disease cases, annually reported in the United States.
Um, it could be quite deadly or quite, um, if not deadly, I think it can be, um, it has, uh, I think more and more, we're kind of learning [00:06:00] about the long-term Lyme disease or what we now think came to term with the, the term post treatment Lyme disease as a, um, as, as pretty debilitating. Um, and as Jason mentioned earlier that it wasn't virus and two-point virus, they can be deadly.
I I'm sure if Jason would like to add more. Yeah. And again, I would say as far as being aware of tick-borne disease, Again, I think that changes depending on where you are here in state [00:06:30] college. If I go out or if my colleagues go out and grab wild ticks and test them 50% of them or more are going to be infected with the Lyme disease pathogen.
Um, so if you get a tick on you, 50 50, that you're going to get Lyme disease. Um, almost everybody that I know has had Lyme disease here, at least once. Uh, I've never had it. I'm very, very anal about checking myself for ticks. If I'm out in the woods, I live in the woods. Um, a lot of people though, kind of aren't, especially, you know, people that hunt and people that do things outdoors, [00:07:00] and it's just kind of, um, sort of part of the part and parcel with, with the lifestyle of living in this area.
So here people are very aware of ticks and tick-borne disease. Uh, but again, it's primarily focused on Lyme disease. They're less aware of some of the other pathogens, such as pulse and virus that could also be. Yeah, down here in Florida, we get key Lyme disease. All right. I had to do it right. No, I, I, my mom always used to put a little front-line on the back of my [00:07:30] neck before I every month.
And, uh, anyway, um, so I guess the other big question is, is it one type of tick per disease or can multiple species of ticks carry the same path? Uh, it depends on the pathogen. So there's some, some bacteria that can be transmitted by multiple different tick species. Other ones seem to be more fastidious.
So the Lyme disease bacteria Borrelia burgdorferi seems to really only be transmitted by, uh, [00:08:00] scapularis and closely related species that like such as . Um, also I was saying, so it is specific as here on the west coast, but those are one of the common names for those ticks, a black legged tick or deer tick.
Um, and here in best, we call it vesting but different species. Okay. So, so do the ticks, how do they get infected? Do they bite you first or by the human first that has the [00:08:30] bacteria and then spread it? Or is there another zoonotic event in there? So generally, uh, for Lyme disease, uh, rodents are the primary vertebrate reservoirs.
And so the, the, the larval ticks, the baby ticks will feed on those roads. Uh, and pick it up, uh, and that, or they can pick it up as nymphs as well. Uh, and then when, when the, the adults, um, feed on a, on a human they'll transmit it to the human, um, I believe humans are dead end hosts for Lyme disease parasite, [00:09:00] which means that a tick feeding on an infected person will not become infected.
And Monica, you can correct me if I'm wrong on that. That's correct. Same as Dieter. Um, although they are very good at transporting picks, they have, in terms of immunology, they are dead host as well as humans. So what are our current strategies for controlling tick-borne illness? Uh, Lyme disease here, um, is mostly antibiotics.
Um, for the most part, if you CA, if you present to the [00:09:30] doctor here in Pennsylvania with a tick bite, they're not even going to test the tick. You can have a tested yourself if they're just going to prescribe antibiotics. Um, because again, you have a 50, 50 chance of that tick being infected. The problems with in the early stages, Lyme disease is pretty easy to treat with antibiotics.
The problem becomes if you have. Uh, chronic Lyme or lime that hasn't been treated, uh, that can get much more difficult to treat later on, uh, ticks are difficult to [00:10:00] control. Um, so you know, you, if you're out in the woods, you need to be just very, uh, cognizant about, you know, having no place in your clothes where they can get in or having repellent on, um, so that they don't attach to you.
And we generally use pirates. Probably when we, when we go out in the woods and a lot of the, sort of the control is basically, um, centered around avoidance of tick bites or checking yourself to make sure that you can pull the ticks [00:10:30] off before they have a chance to transmit. Um, if you do get Lyme disease, then it's, it's treated with antibiotics, uh, for some of the viral diseases like Polaski and virus, um, there really is no treatment other than supportive.
Uh, and those ticks can transmit Polaski and relatively quickly, within maybe 15 minutes of biting, I was going to say, that's also, I think, very geographic dependent. Um, like Jason said in, um, in state park in Pennsylvania, we are, he is it's because it's prevalent. It's a lot of [00:11:00] doctors, a lot of clinicians are aware of lung disease, so they put people on antibiotics.
But if you are in other parts of the country, that Lyme disease is not that common. Uh, many times Lyme disease go unnoticed. And where are the hotspots in the world for, for tick-borne illness? Is it happy valley you really down in ground zero there? Um, for the United States, sort of the Northeast Wisconsin, Pennsylvania, New York, Maine, um, Maryland, um, you start to [00:11:30] get into other tick species as well.
Um, so. That's sort of the general hotspots in, in Florida, you have ticks, but you don't have really the disease. And that has to do more about, um, sort of the, the climate and the lifecycle of the techs, uh, in terms of them being able to amplify pathogens in the population where, because of the. The environment that basically doesn't work, that doesn't work as efficiently.
And you also have things like lizards where if the ticks feed on the lizards, [00:12:00] uh, the compliment and the lizard will actually clear the, the bacteria out of the tick, um, which we don't have up here so much. Uh, and also if you're talking about worldwide, you know, Europe, um, Asia, these middle east can be, um, uh, have, uh, uh, enormous problems with tick-borne pathogens of, of a variety of different, uh, types.
But then they're saying USB hotspot. I think it only thinking about Lyme disease, but if you're not thinking about the, um, kick as agricultural pasts [00:12:30] feeding on cattle, which is a huge problem in, um, in Southern, in south America and Asia and Africa as well, their cattle is a huge industry. Ticks cattle thing.
Specially have caused a lot of damage. Well, that's really great. I finally understand a lot more about ticks. It's always interesting when people fear things like sharps and shark attacks, where mosquitoes and ticks are, seem to be doing so much more damage. So we'll come back on the other side of the break and we'll [00:13:00] talk about ticks and some new mitigation strategies which have come from Dr.
and Dr. Goulian news. This is the talking biotech podcast by collabora, and we'll be back in.[00:13:30] [00:14:00] 
And now we're back on the talking biotech podcast. We're speaking with Dr. Monica Golia news and Dr. Jason Rascon about ticks. Their disease vectors. They're a bigger problem all the time, but now new technology and biotechnology is working on limiting their numbers and their threat. And so that's where the, really where we [00:14:30] got in touch.
Cause I saw on Twitter when I saw Dr. Raz post about the new paper where a Dr. Goulian news, you were the lead author in the study. Uh, chick biotechnology. So what was that paper about? So this paper is specifically about developing tools. So we developed two different methods of editing, um, genes in texts of using CRISPR technology.
So one of the method is the classic method of [00:15:00] injecting. Embryos and then develop and taking them to the adult stage. That's most to Octopod specially insects have done, um, and mosquitoes. This is the, the way to do, to make transgenic mosquitoes, um, same with other flies as well. And so this was one of the major breakthrough because nobody has ever injected pecan views.
Those were deemed impossible to be injected. So this paper now opens the path to [00:15:30] do more work because we have developing mTOR injection protocol and we have used it to do CRISPR knockouts second way to do it as the method that was developed by Dr. Austin slab. Um, and this is. Tool, um, especially for the labs that you don't have this injection.
So this is called a remote control. And in this method, the inject adults, gravid females instead of ambulance. So the car [00:16:00] was taken up by the MTUS within the female before she lays eggs. So we choose these two tools to genetically modify, to show that pics can be genetically modified. Neat. So in that second method, let's talk about that a little bit.
You're you're using like microinjection or something to inject into the body cavity of the female that's gravid and then somehow is injecting the gene editing. [00:16:30] Complex into like, you know, the ribonucleoprotein complex into the female, and then it's kind of finding its way into the eggs and making edits.
So the way this works. So this is a project that my lab been working on for quite a while, um, to basically get rid of the necessity to inject embryos. And so what we have done is we identified a very small peptide ligand. It's about 40 amino acids that binds specifically to receptors on the arthropod.
And we fuse this [00:17:00] peptide basically to anything we want in this case, it's fused to the CAS nine protein. And so you can make, uh, the ribonucleoprotein complex with that modified CAS nine. And when you inject that into the open circulatory system of the female arthropod, um, when she's undergoing retell agenesis, these, these peptides are based on yolk, protein precursor.
And so they're basically the receptor binding region, um, of those yolk protein precursors. And so basically the cause of when [00:17:30] you inject it into the open circulatory system, it gets taken up into the ovaries the same way that yolk protein would get taken up into the ovaries during egg development. And so, uh, the interesting thing, a couple of interesting things is number one, the peptide that we use.
Uh, it's called PTC and it actually seems to function at about 95% of all arthropod species, even though there's no homology, we don't really understand why at this point, um, we're still working on that, but the point is it does work quite well in most [00:18:00] species. And so, um, the same construct works in mosquitoes.
It works in beetles. It works in, um, uh, again here we showed that, uh, Monica and Margaret showed that it worked in. And it's a much easier way of doing it's a much easier and sort of low tech way of doing these experiments because you don't need all of the fancy equipment to inject embryos. We actually use it.
Um, it's with a mouth tube, it costs about $2. Oh, cool. [00:18:30] So, so this is one, so you don't need to have the, uh, fancy microinjection set up like you do when you, you know, work on yeast, that dreads and stuff, you just, you just actually inject it right into the body cab, right into the circulatory system of the, of the, uh, of any arthropod, which that's a pretty broad set of, uh, organisms.
So you could really go ahead and change. Use this kind of mechanism to pretty much target any gene in any [00:19:00] insect, right? Uh, that's the plan and we're actually even moving in my lab beyond insects. At this point, we're working in vertebrates now. Um, Using the similar types of technology, so that to get away from the need to inject, um, you know, vertebrate embryos, which are, or other kinds of techniques that people use.
Oh, that's really, really a great technology because that would seem like such a, such a limiter to being able to do this work. How so were people able to do this before? Or what [00:19:30] were the major barriers? Um, so for the adult injection, nobody really tried before. This is something my lab started back in.
2011. Uh, and we finally got the system working in about 2017 or 2018. So it took quite a while to sort of figure out what we were doing. Um, but we've, we and our collaborators have actually shown that this works. It may be 12 different species, um, all across sort of the taxonomic diversity of arthropods at this time.
Um, so [00:20:00] various multiple species of mosquitoes. We've done it in, obviously here ticks, um, other groups have done this in beetles. We, we, my lab did it in white flies. Um, we've done it in stinkbugs ultra Sophala, obviously. And, um, the actual, just testing the ligand function. Um, we've done that in about 20 different species and I've only found one or two where it actually doesn't work and we had to actually develop it a different type of.
That's really cool though. Cause that makes everything [00:20:30] so much easier. If you can have targeted delivery of the CAS nine and you know, guide RNA to those specific tissues where they can, uh, create heritable changes. So what kind of changes are you engineering or which ones do you hope to engineer to. Uh, affect tick biology.
Well, this is just the big thing right now. We have a lot of targets in mind that we would like to, um, to go after. Um, some of these targets that are related to, um, to community, to [00:21:00] pathogen, to some are of understanding just the basic biology of Texas. Um, interested in reproductive biology. I have had a, um, interest for a long time and insulin signaling pathway in arthropods and a lot of work in.
Mosquito insulin signaling pathway, um, Sylvia, I'm interested in understanding what, how it works in techs. Um, I would say that, uh, you know, it's not just my lab, it's a, the whole tech research community has the tools now. And we can start [00:21:30] answering questions about genetic biology as well as pathogen interactions.
Um, so it's a, it's a wide open field now. To start learning about a whole lot motor Bouche dicks, w what would be a great application? Is it really something like self-limiting ticks so that you could do, like, you know, sterile, insect technique and maybe knock down numbers in a place where there was an outbreak of Lyme or some, you know, other kinds of.
That's quite [00:22:00] possible via not there yet. So, uh, I want to mention that in this paper we have shown that is a proof of principle. Yes, it works. We have only shown no counts so far. We haven't shown a knock ins or insertion or replacement of genes yet that's coming next. So that will be our next step. She do in Dixon.
Again, another thing to keep in mind, dicks have a pretty long life cycle in the lab. They bring it down to about five months, but [00:22:30] it's still quite nosy. We still have to see how to develop mutations in Texas. This was, we only looked at, um, easy to larvae. Um, so the, um, that's again, the future plans is to look at the head of demote mutations.
Um, gene drive takes possible. Um, the. Um, I know they, haven't given a lot of regulations, um, as we are seeing that mosquitoes as well, but, uh, um, tick technology is [00:23:00] not that odd in future, I believe now. Have they done anything with sterile tick technology using radiation or any of the old school tricks or is that something really just limited to mosquitoes and maybe some other kinds of insects?
I don't think they haven't. Yeah, I think that comes more down. Not so much that you couldn't do it. Um, it's, it's really more an issue. I think, of the tic husbandry, where it's very difficult to rear ticks. They take a long time and to rear the numbers that [00:23:30] you would need to do and is just technically very different.
I see. So what about ticky cology though? I mean, I don't even know what they really do or why they're there. And so what is their ecological role and what happens if suddenly you were able to limit their numbers? I think, I think that their role in the environment is to make more texts. They don't really need to do anything more than that.
Uh, you know, they could be food for things, but I don't think getting rid of them is really gonna come. Any kind of [00:24:00] major imbalance, ecological imbalance, um, they're they're ecto parasites. And so there are other types of ecto parasites out there too. If, if anything really specializing on ticks. And I honestly can't think of anything that specializes exclusively on ticks.
Um, there's other stuff out there for them to eat too. So I really don't see that if we were able to, to, you know, Way down the road. Cause we're not there yet. Um, but if we were able to eliminate a tick populations, I don't think it would be [00:24:30] a huge, I worked in a rabbit Opsis right. The model P model plant system.
And so when they figured out how to do floral dipping, where you dip the flowers and Agrobacterium solutions, you get gene transfer events inside the flowers. Um, it sounds almost like you've. Stumbled into that while stumbled. It sounds like you've moved into that same sort of transformational technology that now enables everybody to do really meaningful gene editing experiments.
That really are the gold [00:25:00] standard in understanding gene function, as well as perhaps come up with new applications. That's exactly what. Um, and I, I do they take community in terms of the, sort of the vector biology community. I think mosquitoes are kind of overrepresented the tick. There are a fair number of tick labs, but compared to labs as specialized in mosquitoes, there aren't that many.
And I think part of that is just because it's hard to work on texts, you know, because they're hard to rear and we didn't have the tools. And, and now that we're, that [00:25:30] these tools are starting to be developed. I think more and more people are, are, are going to be. Beginning to enter that space and work on those systems.
Um, although they take back, the biology community is small. There's a quite a large community that works on tick borne diseases. So they they'll be able to use these tools as well, to understand more of the fact inside of work's battles and interactions. Oh, very good. What about other insects? You mentioned this works well throughout arthropods and made a mention of mosquitoes.[00:26:00] 
Is this something that is going to radically change the work on mosquitoes? It could. So there's, there's a fair number of labs that already do sort of genetic manipulation and mosquitoes, and those labs can already do it with embryo injection. Um, so I see this more of not so much of, uh, the remote control, um, adult injection tools.
I don't see those as really revolutionized. Sort of the standing mosquito [00:26:30] labs that do this work. But what it will do is allow people that, you know, either work on systems that are not amenable to, to embryo injection, there are mosquitoes that, that people have not been able to transform yet because the husbandry is difficult.
Um, but beyond mosquitoes, even, I think it has significant potential for bringing the power of. Genetic modification and CRISPR to non-model systems. And that's really the whole point of this project. It's funded by the NSF edge program, which is specifically [00:27:00] for developing genomic tools. And so one of the things that we were able to do, like I said, um, uh, last year or the year before we were able to, to genetically engineer white flies using this technology.
And, um, there's maybe only one or two other labs in the world that can actually do embryo injection and white fly. But using this technology, anybody can do. Um, and you know, we've set reagents, um, to labs that are in Africa and south America that just don't have the money to buy the equipment needed [00:27:30] to do embryo injection.
Um, but they can do this. And so it's really opening up the power, uh, and expanding the ability of, of, of laboratories, uh, to use these genomic tools and genomic techniques without having to shell out tens of thousands of dollars for, um, the, the embryo injection equipment. Yeah, I love that. Anytime we can democratize science by allowing better tools to be more accessible, it makes huge difference.
And what do you think the first applications will be? [00:28:00] Well, what do you hope the applications will be perhaps in ticks that may limit tick-borne illness? Are there genes that ticks maintain that specifically? Make them good vectors for harboring these specific bacteria? I think they'd have been, yeah.
There have been quite a bit of work trying to, under to identify. Targets for antique vaccine. And I can see a [00:28:30] really easy way using this technique now to, um, understand these functions of these genes that people have been, you have identified in the past, but didn't have a direct way of testing the hypothesis.
So, um, hopefully we will have better vaccine candidates now since.
So Dr. Goulian nous and Dr. Jason Rascon, if people want to learn more about the [00:29:00] project and about how to transform arthropods, including ticks and what's coming up and tick applications. Where can they learn more? And where do they follow you? On social media? They pays a pretty good resource. Um, the, there will be more publications out.
So follow us. Um, either on Twitter, I am ethically in this lab. Um, and also I met, I maintained, um, our lab website to UNR. So that's another way to, um, learn more about our work. [00:29:30] And for me, you can follow me on Twitter at, um, Vectren. And also the remote control project has a Twitter account, uh, remote gene edits.
And so we're always posting information there. Um, and if you're interested in more, if, if any of the listeners are working on an insect or arthropod and they want to try, uh, the remote control technology, they can just send me an email. We've sent reagents to probably 60 different labs in at least [00:30:00] 25 countries across the world.
Um, that are all trying this. So if anybody wants to try it, just send me an email, but that's wonderful. And that really reaffirms the NSF mission with the edge project where the edge type projects. Right? Absolutely. The whole point of it is, is, uh, tools for the research community and resource dissemination, uh, is baked into the actual product.
So it's all part of it. So we'll send this stuff out free of charge. We're not charging for anything. [00:30:30] Yeah. And I really liked that because this is, this really does reaffirm, why NSF exists and the things that they are fueling and basic science research that enabled more people to study the systems that they're interested in that have real application and real consequences in the real world.
So this is really great. So congratulations on this one. Thank you very much for Monica and Jason for joining us. Thank you. And thank you for listening to collaboratives talking biotech podcast. [00:31:00] Write a review on Spotify, iTunes, or wherever you consume. Podcast media. The more reviews we have, the more likely people are to follow the podcast.
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