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HomeInVivo Biosystems Blog17 Minutes of ScienceSeventeen Minutes of Science: Comparing platforms for testing anthelmintic drugs in C. elegans

Seventeen Minutes of Science: Comparing platforms for testing anthelmintic drugs in C. elegans

Tune in weekly to our virtual series "Seventeen Minutes of Science" every Tuesday at 11am PST / 2pm ET where we go live on Facebook with a new guest each week to talk about how science and biotechnology is woven into their lives for (you guessed it) 17 minutes!

For episode 44 of 17 Minutes of Science we are joined by Dr. Janis Weeks. Janis is a co-founder and chief global health officer at InVivo Biosystems in addition to being a Professor Emerita of Biology at the University of Oregon.

Dr. Weeks is an expert in anthelmintic research, with experience and expertise in technology development for drug screening platforms, including anthelmintic (anti-nematode worm) drugs for human and animal health; nematode neurobiology and genetics; synaptic physiology; neural circuits for behavior; insect neurobiology; tropical infectious and parasitic diseases.

Janis has taught neuroscience in Africa for 25 years, prompting her interest in neglected tropical diseases such as helminth infections. With funding from the Bill & Melinda Gates Foundation, she began working on parasitic nematodes to complement work in C. elegans. Her current research focuses on new technologies to advance research into anthelmintic drugs for animals & humans.

Dr. Weeks joins us to talk about her recent paper which has been accepted pending minor revisions, Comparison of Electrophysiological and Motility Assays to Study Anthelmintic Effects in C. elegans.

Transcription

Penny Melquist (Host): [00:00:10] Welcome, everyone my name is Penny Melquist, I work at InVivo Biosystems in business development, but I'm formally trained as a scientist. So some of you have talked to me in a science role in business development. But today on 17 Minutes of Science, we're going to be talking to Dr. Janis Weeks. Welcome, Janis. And our topic is going to be comparing platforms for testing implemented drugs in C. elegans. So this will be great. You can talk to us about your collaboration with Bayer. But first, I wanted to do a quick bio about you, Janis. Janis got her B.S. in Applied Life Sciences from MIT. She did her PhD in biology and neuroscience at UC San Diego, your postdoc at University of Washington. You were a faculty member at UC Berkeley. And in 1988, you moved your lab to the UO [University of Oregon]. Yes, lucky us. And then [you transitioned] from the UO as a full professor to focus on InVivo Biosystems. So we're very fortunate. And um, your research; so, you have always worked with invertebrate species, leeches, insects, nematodes used primarily in electrophysiology. You've done a lot of work on the ScreenChip System, but you focused on identifying neural circuits for behavior with an emphasis on hormonally mediated synaptic transmission and plasticity. And Dr. Janis Weeks and Dr. Shawn Lockery, long time colleagues at the UO Neuroscience Institute, founded NemaMatrix in 2011 as a spinoff from the University of Oregon. And another interesting fact about Janis is that she taught neuroscience in Africa for about 25 years with her interest in neglected tropical diseases, specifically helminthic infections. And you also, I never knew this about you Janis, that you got funding from the Bill and Melinda Gates Foundation. So [you] were working on C. elegans, but it was a nice compliment to focus on parasitic nematodes. And your current research, aside from all of the other things that you do for us, is to focus on new technologies and platforms to advance research on implementing drugs for animals in humans. And first and foremost, I really have to say it's an honor to interview you today. I see you periodically and we have meetings together, but I really appreciate all that you do for our company and our colleagues serving as a mentor and what you do around the globe. So thanks, Janis.

 

Dr Janis Weeks (Guest): [00:02:36] Well thank you Penny.

 

Penny Melquist (Host): [00:02:39] All right, so I'm going to start our timer, 17 minutes, and it's probably going to go by in about 17 seconds, but let's go ahead and get started. So why don't we talk about, if you could, you know, sort of talk to us about what are anthelmintic drugs.

 

Dr Janis Weeks (Guest): [00:02:56] Great, well, again, thanks, Penny, and I'm so honored this is the first time you've done an interview and I'm so honored that I'm the lucky one. So, yeah, let me start by explaining what anthelmintic drugs are. So Helminths, the term helminth, means parasitic worms of different types. So antihelminthics or anthelmintics just means drugs that kill worms. So the worms are often parasitic, and [there are] these various chemical classes of drugs, but in all cases they are treatments for animals or humans to rid them of parasitic worms.

 

Penny Melquist (Host): [00:03:38] Oh, interesting. So when you think about, you know, C.elegans and non-parasitic nematode and parasitic nematodes in your studies, you use C. elegans. So maybe you could elaborate a little bit more about, you know, not using parasitic worms, but using C.elegans, and how that parallels and joins together.

 

Dr Janis Weeks (Guest): [00:03:56] Yeah, that's a really active question in the research community now. So one thing about parasitic nematodes, and I have worked on parasites, so hookworms and ascaris and those and other mammalian parasites have to be generally raised in mammals. And so, for example, the hookworms I worked on, which infect humans they can be raised in the lab in hamsters. But in general it's really expensive and complicated to raise mammalian parasites in the lab. You need to have mammalian hosts and it's expensive and complicated. On the other hand, those are the worms we want to kill. So working on C. elegans, there's certain, you know, actually a high degree of genetic homology in the genome of C.elegans and the parasites. So sometimes if you have a gene target targeted by a drug, it's also present in C.elegans or - this is something we do at InVivo Biosystems. We can insert parasite genes into C.elegans to study them. But anyway, so there's - C.elegans are valuable in a lot of ways. For example, finding hypotheses about potential new drugs or how they work, but then they can be followed up in parasitic species. So the field kind of moves [00:05:19] ahead... [00:05:19]

 

Penny Melquist (Host): [00:05:20] Yeah.

 

Dr Janis Weeks (Guest): [00:05:21] You know, C. elegans as a simpler, more tractable system then the actual parasites.

 

Penny Melquist (Host): [00:05:27] Sort of like a precursor. It can give you some give you an indication of kind of what you might see. And I know that for a long time you have worked with InVivo Biosystems with Bayer Animal Health in Germany on a lot of a similar area. Could you maybe elaborate on what you were working on in kind of what your hypothesis was?

 

Dr Janis Weeks (Guest): [00:05:52] Yeah, well, this dates back to Bayer Animal Health in Monheim, Germany. Actually, it was acquired by Elanco last year. So they're now out of the Bayer family, I guess you would say. But for many years now, I've been meeting up with a Bayer scientist, Daniel Kulke, who was in Germany, but we would meet at conferences and so on. And we eventually - so over the years and he, Daniel, and his colleague Iring Heisler came to Eugene and met with us and saw our experimental platforms. Then I spent some time in Germany visiting them and talking. And eventually we came up with this collaboration, which had to do with comparing three platforms that are available to test and characterize anthelmintic drugs. Two of them are electrophysiological, which is my specialty, and then one of them is a platform to measure motility. And just, I'm going to have to explain this at some point so I will now. So the electrophysiological methods, and these were experiments done on C. elegans, so when Shawn Lockery and I founded the company, it was based on a microfluidic device that could record electropherograms. That is, the electrical signals from the pumping of the pharynx. And the original device was an eight channel chip where you could record EPGs or electropherograms from eight worms at a time. That rig is available at InVivo Biosystems for work that we can do for others, but it's not commercially available. But then the other two platforms we looked at in the study are the ScreenChip, which is a one channel EPG recording device that is -that we do make at IBV and then the other platform is called the wMicroTracker, which is a multi-well format device that measures where motility by - when the worms break a little micro beam by moving, it's counted. So what the project ended up being was to compare these three platforms to see which are best adapted for which kind of experiments and Bayer had the ScreenChip and MicroTracker in their labs there. And then a postdoc, Steffen Hahnel, came to Eugene and did experiments with us for a few weeks using the eight channel. So that was the Project.

 

Penny Melquist (Host): [00:08:39] Oh nice, and is it still ongoing or is it wrapping up? I'm trying to remember, I know your paper.

 

Dr Janis Weeks (Guest): [00:08:43] Yeah, we pretty - the project, we finished all the experiments and the paper, we're returning it with revisions at the end of this week in International Journal of Parasitology, Drugs and Drug Resistance. So anyway, that summarizes all the work that came out of this collaboration.

 

Penny Melquist (Host): [00:09:04] Yeah, nice. I'm curious, was there anything that really surprised you out of all of the work that you did?

 

Dr Janis Weeks (Guest): [00:09:14] Well, I'd have to get into some of the results. Surprised, I guess, one of the main findings we found. I mean, many people use motility. I mean, there's standard assays people use to look for drugs that will kill worms. They can look at development or reproduction or motility. But electrophysiology can be especially useful because most of the drugs out there act on ion channels. So an electrophysiology readout, it's going to be lower throughput, but often provides more specific info. So what I - one thing that surprised me and pleased us about our results is that we found that electrophysiological recordings could illustrate drugs or target specific phenotypes. So we found that some electrophysiological signatures could separate this class of anthelmintic drug which acts on one ion channel from another class that we studied. And so that was really gratifying. And I don't know if it's surprising. It's what we hoped for, but we were pleased.

 

Penny Melquist (Host): [00:10:28] Yeah, well, that's good, because that's - it's really never good to be surprised when you're doing research. So this is a positive surprise. It's interesting you think about using the two platforms, you know, although they're very different and - doesn't sound like one really favored the other, but they nicely complimented themselves to sort of give more of a fuller picture of what was going on.

 

Dr Janis Weeks (Guest): [00:10:51] Yeah, one outcome of the paper, and actually the reviewers asked us to add a table of this, is we identified strengths and limitations of all three platforms so that investigators can now pick what best meets their needs. So that was a valuable thing for us to find out for ourselves, but also for anybody that wants to use these methods.

 

Penny Melquist (Host): [00:11:21] Nice. So the next step: the papers being reviewed and edited. What about any further studies that come out of it that you can elaborate on?

 

Dr Janis Weeks (Guest): [00:11:33] Well, we're not -I mean, unless we, yeah. We don't have any plans to continue this collaboration with with Bayer Animal Health, although we would be happy to. But anyway, that's not in the works right now. But moving forward, we're just a lot more confident about, you know, both in-house for us, but also for people out there that have micro trackers or ScreenChips. You know what, what aspects of them are good for which sort of experiment, depending on what you know, what you want to find out. And then again, this also sets us up for more of the eight channel EPG where that we can do in-house in terms of when is it most appropriate as a tool based on what we want to accomplish.

 

Penny Melquist (Host): [00:12:22] Yeah, I mean, it definitely seems like, I know you've given talks about this, but the interesting research that's being carried on, especially with funding from the Bill and Melinda Gates Foundation, the research into parasitic, uh the parasitic world is really expanding. Wouldn't you say that it's an accurate assessment of past couple of years?

 

Speaker3: [00:12:41] Yeah, you know, a lot of, I mean, I'm guessing maybe a lot of the funding say for international global health, some of it's now, I think, diverted off for COVID-19, which is, you know, a more acute emergency. But in fact, many helminth infections cause huge morbidity, not so much death, but just chronic illness and stunting of children. And, you know, there's just a third of the world's population carries a parasitic infection. So it's a huge issue and it's often been neglected. How important this is. But one interesting aspect is that all of the drugs, anti-parasitic drugs, antihelminthic drugs used on humans came from veterinary medicine. So the funding and the motivation to develop drugs for, say, companion animals, you know, if we have dogs or cats, they've been wormed as puppies or kittens, agricultural animals, cattle, goats, horses, all those. There's a huge need for new drugs because of drug resistance. And then the way it works, those then typically set up a way to make those drugs work for humans. So I think there's a lot more investment in animal antihelminthic drug development right now. But that always is a plus for human infections as well.

 

Penny Melquist (Host): [00:14:12] Yeah, yeah. Well, that nicely segues into my other curiosity question. If you could maybe talk about your work in Africa, you know, working with parasitic research and educating people in neuroscience, it nicely complements what you do for us at InVivo Biosystems in the sense that you are the Chief Global Health Officer, which I didn't say that earlier. So my apologies. And co-founder. If maybe you could talk about that in our last couple of minutes. We have five minutes left, so.

 

Dr Janis Weeks (Guest): [00:14:42] OK.

 

Penny Melquist (Host): [00:14:42] You're doing great. Yeah.

 

Dr Janis Weeks (Guest): [00:14:44] Yeah, well, I just out of the blue got invited right after the end of apartheid in South Africa. I just got a phone call asking me if I would like to come in and teach in the first neuroscience workshop coming into South Africa after apartheid. And that was in 1996. And that just flipped a switch, really. And so since then, I've been involved with the International Brain Research Organization, which offers, you know, research and education, capacity building in neuroscience really all over the world, but especially on low and middle income countries. And I've sort of specialized in Africa. And the last decade or so, a small team of us have focused on a workshop called Teaching Tools, which takes a junior, young, beginning faculty members and works on, you know, new, innovative, integrative ways to teach neuroscience and neurology. So we've been running that workshop. We didn't run it last year, obviously, because of COVID, but we're thinking about doing it this year. But it was being in Africa year after year for those workshops. And then I'm involved in Zimbabwean music. So I've spent a lot of time in Zimbabwe and just seeing these diseases firsthand, I mean, that's what really - I mean, that's what really just changed my research directions, you know, in the mid-2000s to say, how can I take my neuroscience expertise, and even though what I was doing before I loved, you know how can I apply it to an applied global health problem like parasitic disease? So that's what got me here.

 

Penny Melquist (Host): [00:16:29] What do you what do you think your next steps are going to be?

 

Dr Janis Weeks (Guest): [00:16:32] Mm hmm. You mean career-wise, research-wise, travel?

 

Penny Melquist (Host): [00:16:40] Oh, just like Africa, because, you know, your whole career in neuroscience, physiology, parasites, Africa, these are all related. And so it seems like there's another, you know, move after that, tying all of these things together.

 

Speaker3: [00:16:56] Well, I guess I think for now, and especially with all the uncertainty with the pandemic, I'm just going to keep being, you know, the parasite contact at InVivo and, you know, work with customers and researchers who are interested in anthelmintic, drug development or other drug development as well. And then I'm going to keep going to Africa, teaching again that may be possible again starting this fall. I also, even though I'm retired from UO, I come back and teach one course a year on tropical diseases in Africa for biology students. So I've kept doing that because it's a really great way to, you know, alert our students about all the important research questions and, you know, health problems out there that hopefully they can graduate and go out and help solve.

 

Penny Melquist (Host): [00:17:52] Yeah, definitely. And I'm curious, are there any, like anthelmintic drugs that are, you know, at the top of your minds in terms of popularity, like top 2, top 3?

 

Dr Janis Weeks (Guest): [00:18:02] Well, there's a lot of drugs that are in the benznidazole class like albendazole and so on. And those drugs act by destabilizing microtubules. But the other well, there's two other classes, really, and these are ones we used for the study with Bayer Animal Health. One is the avermectin drugs like ivermectin. You've probably - if you have pets used ivermectin, to deworm them, so that class of drugs, they act on glutamate gated chloride channels on muscle. And then the other class that we've worked on a lot is drugs that activate acetylcholine receptors like Levamisole, and that's an agonist of ACh receptors. And both of those classes of drugs cause paralysis of worms and then say for intestinal parasites, once they're paralyzed, they can just be swept out of the digestive tract. So I favor - I personally, as an electric physiologist, favor the drugs that act on, you know, neuromuscular transmission or synaptic targets. But there are other classes out there that act, you know, that perturb other aspects of worms' physiology.

 

Penny Melquist (Host): [00:19:20] Nice. Well, we have about 20 seconds left, and I just want to take the time to thank you again for being such an amazing resource. I always am sending you emails and questions about parasitic - questions that I have from, from other people. And just out of curiosity. You know, you talking about Africa. So thank you so much for being an amazing colleague, a fantastic mentor and an excellent example of a woman in science. You're amazing.

 

Dr Janis Weeks (Guest): [00:19:48] Aw, please.

 

Penny Melquist (Host): [00:19:49]  [00:19:48]And just keep on keeping on and don't hesitate to use Dr. Weeks. I'm going to use it on you. [00:19:55]

 

Dr Janis Weeks (Guest): [00:19:56] Thank you.

 

Penny Melquist (Host): [00:19:58] And I want to take 20 seconds to give a shout out to the person that produces and directs and edits and curated this entire series. Hannah Houston, one day you're going to be interviewed and I'll make sure that that happens. But without Hannah, this would not happen. She does all the behind the scenes work, but she's got several screens going on right now so that we can livestream this. So thank you, Hannah. Thank you, Dr. Weeks. It's a pleasure to be your colleague. And tune in next week for another great show and we'll be back. Thank you.

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