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On episode 50 of 17 Minutes of Science we talk live with Dr. Ken Dawson-Scully from Florida Atlantic University about his research into how invertebrates protect their brains from environmental stresses, and how he has moved from academia to entrepreneurship by embracing failures.
Dr. Ken Dawson-Scully is currently a Professor of Biological Sciences at Florida Atlantic University where he also serves in the role of Associate Vice President for STEM Partnerships and the Director of the FAU Max Planck Honors Program. He is also the Head of Institutional Partnerships at the Max Planck Florida Institute for Neuroscience. Dr. Dawson-Scully’s research investigates neuroprotection from environmental and artificial cellular stress in the model organisms, the fly D. melanogaster and the worm C. elegans. He currently has funding from the NSF and the NIH and has produced several patents which has led to development of spin off companies like Eco Neuorologics Inc. in 2013 and Neuropharmalogics Inc. in 2015.
Tune in to learn more from Dr. Dawson-Scully about his research.
Dr. Chris Hopkins (Host): [00:00:10] Hello there, Chris Hopkins here on 17 Minutes of Science. This is the show where we explore the world of science and how it affects the starting academic and the seasoned professional. Today, we have Ken Dawson-Scully with us from Florida Atlantic University. Hi, Ken.
Dr. Ken Dawson-Scully (Guest): [00:00:26] Hey, Chris. How are ya?
Dr. Chris Hopkins (Host): [00:00:29] Good, doing good. Well, let's go through a little background on you. Ken is currently a professor in biological sciences at Florida Atlantic University. He's an associate vice president for STEM Partnerships, he's the Director of the FAU Max Planck Honors Program. He's also the Head of the Institutional Partnerships for the FAU Max Planck Florida Institute of Neuroscience. Ken's research investigates neuroprotection from environmental and genetic cellular stress. And he uses multiple model organisms such as the fly, the worm, the zebrafish. And he currently is funded by the NSF and NIH and has produced several patents. And this has enabled him to generate two spinoff companies, Eco Neurologics and Neuropharmalogics, with only 17 Minutes of Science to cover a lot of ground. Let's jump right in. So the first question for you, your research combines behavioral genetics, Electrophysiology and bioimaging. And this allows you to explore how invertebrates protect their brains from environmental stresses. Can you tell us a little bit more about how this research and how these techniques work together?
Dr. Ken Dawson-Scully (Guest): [00:01:34] Yeah, you know, it's, it's I think we're always trying to be productive as possible in the lab, and we've always gone after a wide array of pathways and targets for trying to understand, um, a: how certain organisms can deal with cellular stress much better than others. For example, insects are they quite literally can deal with huge range of temperatures from almost freezing to, you know, up into the 100 degrees Fahrenheit range. Their brain changes at that temperature through that range, um, with humans - we can only do it through a few degrees without going into a seizure ourselves or having brain damage. How do they do it? How do they cope? How do they adapt to that? And are there ways in which we can learn from that to apply them for some sort of at least medical outcome? Same thing with low oxygen. You know, do you ever think about what happens to a fly or even a butterfly when it rains? You know, I would say I fly, they are adapted to actually drown in the water. And the way they've done that and what we've seen in the lab and other labs is seen is they'll literally shut down their nervous system in response to low oxygen stress. It puts them into a both a physiological and behavioral coma. But then, but then when the water abates and other spiracles are open and they could respiration again and get normal oxygen, they can fly away. We've we've done this in the lab. We've we've taken fruit flies and drowned them underwater for days at a time. Five days. We'll dry them off and they look like mulch. It looks like there's no hope of ever getting these insects back, but they'll wake up, their wings come up, they dry off and then they fly away. So for us, we actually use behavior as our initial screen to identify initially either a gene or a drug that may allow for animals to do something that they normally can't or that causes a problem that they normally don't have. And what I mean by that, we might look at a compound or a gene through a screen. And if we're looking at anoxia tolerance, we'll look at animals that knock out quicker. Those are of interest to us because we want to understand genes that might be responsible for animals being able to deal with prolonged anoxia, which is low oxygen or no oxygen - or ones where instead of going into that coma, they they they don't go into the coma until much later. And to try to understand what genes control that. One of the cool things we found with our research, at least with behavior, is that there's always a cost benefit system involved. Like if you cause protection of a behavior, it'll cause a problem elsewhere. So behaviors are a gateway to try to find our initial findings, whether in genes or drugs. And then we move on to synaptic transmission. Uh, in the lab we do that with the fruit fly neuromuscular junction. We work with the larval stage fruit fly and we can actually look at glutamatergic neurotransmission, which is the same as fast neurotransmission that happens in the human brain, and then be able to look at differences when it comes to that, either under stress or not under stress with the effect of that or drug that we're looking at. And then once we see even a phenotype with synaptic transmission, we can go one step further and look at cellular imaging and try to understand the mechanisms that are pre synaptic transmission and determine whether ion channels or ion handling, for example, calcium plays a role and what we're looking at. So behavior is our big catch all. And then we - and that's usually the faster experiments. And then it comes into the the harder, slower experiments of synoptic transmission and then calcium imaging. And so our lab is really interested in trying to find these pathways, but then also understand why they work the way they do, and the mechanisms which they affect.
Dr. Chris Hopkins (Host): [00:05:21] All right, well, that that definitely was a nice integration of the genetics and electrophysiology and bioimaging, actually, electrophysiology this is one area that maybe needs to have a little more, uh delving in, and its actually as part of our some of the collaborations we've done, and that is the experiments you do with electroshocking the C.elegans. So can you tell us a little bit about about what that, you know, what that experiment is and how it's sort of set up and how the heck did you come up with that idea?
Dr. Ken Dawson-Scully (Guest): [00:05:52] Yeah, totally. So actually, I would say using electroshock is actually, as much as it's related to electrophysiology in principles of physics it's actually a part of a behavioral screen. Very early on, in about 2014, we were, we were very interested in trying to understand, I guess, seizure models in fruit flies. Fruit fly, was our main model organism, and that's the one we we normally work with in the lab up until 2014 or 2015, for the reasons I'm about to tell you. There's a guy named Richard Baines, and he had developed and published an article using Drosophila fruit fly larvae and electroshocking them and then showing that animals that were susceptible to shock as adults, and they called them seizure sensitive genes or bank sensitivities, he was able to replicate this by shocking larvae with a positive and negative electrode and then being able to see a behavioural difference there. And we really got attracted to that assay because we found that with a lot of our protective pathways, they're responsible for ionic homeostasis, both ions on the inside of the cell versus the outside of the cell. And so when a human or an organism undergoes a seizure, this imbalance occurs with that homeostasis. And so we thought this would be a great target for looking at some of our genes and drugs, for potentially either making it worse or making it better. When we did it genetically with the fly, it worked really well and it was able to translate into what we had looked at with synaptic transmission as well. But when we started using drugs, we had to use a fruit fly larvae. And if you've ever seen one of these things up close, they're there about the size of a grain of rice, but they're like quite literally a tank. They've have a very, very thick cuticle. They have mouth mandibles that that they can eat with as they move around with their locomotion, with their with their, I guess as something would locomote as a as a larvae. And we call it crawling, but I wouldn't call it crawling per say. And then it has spiracles that allow it to respirate, but they're very sensitive to any change in the environment so they can close rapidly and shut themselves off in the larvae. They have this really cool respirating mechanism. They have trachea underneath the cuticle and they hold huge bags of air so that the larvae can delve into liquid media, for example, and be able to be in that media for a very long time because of the air that's left over in the tracheal system. So when we started adding drugs to these animals either exogenously just on the acute cuticle or in their food, we got all these sorts of mixed results and we couldn't find a reliable way to introduce a drug and then be able to do a behavioural test on the animal, like electroshock, for example. So we had this wonderful collaborator that's in the lab right next to my own here at for Atlantic University is named Dr. Kailiang Jia. He is an expert at C.elegans, and his entire program is with C. elegans. So we were trying to figure out a way, is there a way we can actually replicate this experiment using C.elegans? We entered into a collaboration with them, and we also entered a collaboration at the same time with a C.elegans Lab at Scripps Research Institute with a guy named Brock Rill, who's now at Seattle Children's Hospital. And over time, a brilliant Grad student of mine, Monica Risley, came up with a way to actually have a bunch of C.elegans thrashing in a liquid medium with a positive negative electrode, shocking them at forty-seven volts for three seconds and then allowing them to undergo a number of convulsions. And then they returned back to this sinusoidal movement, the thrashing, they call it as a behavior, and it's a coordinated thrashing. So we're looking, for example, for this coordinated movement and then it goes completely uncoordinated. That's the seizure. And then it comes back to a coordinated movement. We, uh, we found that we can actually treat these animals through their cuticle with drugs, which was super easy. And clearly they're thrashing in a liquid media. So we would put them in the liquid media, the saline, for 30 minutes in the concentration of a drug that would normally work in an animal in, in vivo, for example, or in vitro. Sorry. And so that in vitro concentration translates in vivo for these animals, which is quite nice. But we still do the dose response groups. And we actually came up with a way in which we tested a number of human FDA approved antiepileptic drugs on these C.elegans, and they actually worked, and it was a brilliant experiment, giving us a new model for trying to uncover either drugs or genes that could rescue the time or elongate the time for this electroconvulsive. So what the neat part about that was, is that not only did it give us a new way to look for antiepileptic drugs, which I think is really needed out there every year, there's less and less antiepileptic drugs developed. And the very best one today is no better than the one in the 1800s that was discovered. However, the side effects are much different. That being said, not just antiepileptic drugs, but also we can actually look for neurotoxins and we're even going after ways in which we can look for potentially antidotes for things like bioweapons, where they could affect synaptic transmission, for instance.
Dr. Chris Hopkins (Host): [00:11:19] That is a nice story on the electroshock and how it's basically - you've used a series of collaborations and it started you on multiple animal models. And we, at InVivio, are quite enthusiastic about C.elegans And zebrafish, and we think that the dual-animal model approaches is intriguing for giving you rich data sets. You know, you use some of this data in some patents. We have some medical treatments for febrile seizures and migraine, you have two patents in that area. And you've also got some companies you've started. And we have about five more minutes, by the way. It eats up 17 really quick.
Dr. Ken Dawson-Scully (Guest): [00:12:06] Time goes fast here.
Dr. Chris Hopkins (Host): [00:12:08] It does. It does. Can you tell us a little bit about sort of how the patents in your - how you're translating this findings, you're getting down?
Dr. Ken Dawson-Scully (Guest): [00:12:19] Yeah. So right now, our lab has three granted patents. The first one was on febrile seizure, like you mentioned, and that's just allowing a nervous system to be resistant to temperature change. And for a medical utility, I believe it's five percent of all children in the world under the age of 10 will undergo a febrile seizure at some point. And there isn't a link, a hard link, for that for for people undergoing epilepsy. But it clearly shows that individuals have a sensitivity to like a fever, for example, will lead into a seizure. And we believe at the cellular level we were able to figure out how to ameliorate that, or rescue that, and that led to a patent. We developed a second patent about anoxia and then being able to protect the brain from a stroke like type injury. And in that same patent, we actually talked about spreading depolarization or spreading depression, which is a is a heavy cause of actual migraines. And so, the two spin-off companies you're talking about, Eco Nuerologics, was looking at a utility for stroke. And then a few years later, we went after another company that looked at utility for migraine treatment. And that was, that was looking at a way to either prevent migraine or stop migraine cold. And, you know, we could talk for a long time about that, but we went after an orphan drug mechanism for that. And so the FDA has this great mechanism that you can go through: less trials, less investment and look at a more potential business model, if you're going after disease that only affects 200,000 Americans or less, so we went after hemiplegic migraine for that. The third time, that we don't have a company, but we're working with companies now, I don't think we can disclose them. But we actually came up with a novel compounds, medicinal chemists, um was looking at neuroprotective like resveratrol, and we actually produced a number of compounds that were very similar to resveratrol called resveramorphs. And we found one so potent that it works at full efficacy at a hundred concentration. And so that seems to protect synaptic transmission from a number of acute stresses. And we're still looking at that for potential human use, which is, which is really great.
Dr. Chris Hopkins (Host): [00:14:37] That is, that is a nice translation of your findings, you know. It can be quite challenging and obviously it sounds like you're dabbling with the entrepreneurship, and that's something that as a founder of our company, I've taken that journey.
Dr. Ken Dawson-Scully (Guest): [00:14:58] Right. So how many how many failed companies did you have before you got a good one? And so that ends up being the problem, right? So are both companies Eco Neurologics, and Neuropharmalogics, they didn't quite make it. Like, you know, we had initial investment, we went through a number of interesting findings to bring us to the next level, potentially for R&D, for FDA. But there was always some sort of hurdle that we couldn't surpass and that ended up leading to failure. So I'm two down. I heard that one out of 10 work, so I think we have eight more to go. But I think you've probably been down this road yourself, right?
Dr. Chris Hopkins (Host): [00:15:34] Yeah, yeah, yeah, so far I started one that, that actually ended up exiting more or less through a merger and then I had a second one I did that failed gloriously. So so I've already burned up my one of ten. So, I've got to keep that one running.
Dr. Ken Dawson-Scully (Guest): [00:15:53] That's right.
Dr. Chris Hopkins (Host): [00:15:56] Let's see. We have - oh shoot. We're just basically got about a minute left and had a couple more questions. Is there - we take questions from the live audience. If anybody wants to drop something in the chat, we might be address it. If we can't address it a little bit, we can address them later. You know, you've you just give us a little background on some of your history. Just real quick. I wanted to talk about this thing, the cysteine-string, but I'm not sure - you got a full minute to try and talk about -.
Dr. Ken Dawson-Scully (Guest): [00:16:23] I don't, I don't think we can fit that in in a minute. But I can tell you, you know, as an academic trying to spin on a company, the biggest challenge is trying to find outside partners that are really experts in the field. And so I would say that's one of the biggest challenges. And you really got to spread your network to do that. And so we did that over time. The other thing is funding. And so there's great mechanisms like SBIR grants through the NSF and NIH or ETTR grants and then clearly venture capital. So those are always the challenges for us.
Dr. Chris Hopkins (Host): [00:16:53] Right. And yeah, we do a lot of SBIRs. And so that is something that is has been a vital vehicle for our - not only just sort of generation and existence, but it also feeds and fuels our innovation. So those are very important mechanisms coming from the from the NIH. Well, Ken, it looks like we've hit our seventeen minutes. It's been a delightful conversation. I've learned a lot from you here today. So thanks so much for speaking with us.
Dr. Ken Dawson-Scully (Guest): [00:17:23] Thanks for having me, Chris. It's really great to talk to you.
Dr. Chris Hopkins (Host): [00:17:26] All right. Thanks again. Thanks a lot.