February 2022 — Greg Suh

You are what you (don’t) eat

Dr. Suh is an Associate Professor at the Korea Advanced Institute of Science and Technology (KAIST), as well as New York University. His research delves into the innate circuitry that drives our behavior to seek out necessary macronutrients. 

January 2022 — Vassilis Pachnis & Catia Sternini

The gut that heals

Dr. Vassilis Pachnis, M.D., Ph.D., is a Senior Group Leader at the Francis Crick Institute in London. His team is pioneering our understanding of how enteric glia and neurons join their efforts to move the gut forward through development.

Dr. Catia Sternini, M.D., is a Professor of Digestive Diseases at the University of California in Los Angeles. Her group studies how receptors are trafficked in enteric neurons. She was one of the first to describe that the gut has taste receptors.

November 2021 — Michael Schwartz & Herman Pontzer

Evolving views on obesity

Dr. Schwartz is a Professor of Medicine and co-director of the Diabetes Institute at University of Washington. His team is on the forefront of understanding how our bodies regulate sugar to maintain the energy we need to moving forward.

Dr. Pontzer is an Associate Professor of Evolutionary Anthropology and Global Health at Duke University. He is an internationally recognized researcher in human energetics and evolution.

October 2021 — Jaap De Roode

Of plants and self-medication

Dr. De Roode is a Professor of Biology at Emory University. He is perhaps the world’s foremost expert on monarch butterflies. His team is documenting how these beautiful creatures use plants for self-medication to treat themselves and their offspring against parasites.

September 2021 — Temple Grandin & Andrew Huberman

Thinking in pictures: Speaking science

Dr. Grandin is a Professor of Animal Science at Colorado State University. She has championed efforts to improve animal welfare. And has leveraged her knowledge to expand upon our understanding of human behavior. In addition, she is a spokesperson for Autism Spectrum Disorders. 

Dr. Huberman is a Professor of Neurobiology at Stanford University. He has pioneered efforts to understand “how the brain changes with experience and how to repair brain circuits damaged by injury”. Beyond the lab, he is the host of the stellar Huberman Lab Podcast where he discusses actionable scientific knowledge to improve every day life.

Apr 2021 – David Virshup & Judith Eisen

On Stem Cells and Neurodevelopment In the Gut

Dr. David Virshup is the director of the Programme of Cancer and Stem Cell Biology at Duke-NUS Medical School as well as a professor of pediatrics at Duke University. He Received his MD from Johns Hopkins, followed by a residency in Pediatrics and a fellowship in Pediatric Hematology/Oncology. He established his independent laboratory at the University of Utah, where he was an endowed chair at the Huntsman Cancer Institute. In 2007, he moved to Duke-NUS in Singapore to help establish the Cancer and Stem Cell Biology programme. He is Elected to the: American Association for the Advancement of Science and the Association of American Physicians. His research focused on signal transduction, with an emphasis on both Wnt signaling and circadian rhythms, and his laboratory has collaborated to develop a small molecule inhibitor of Wnt secretion that is now being tested in human clinical trials.

Dr. Judith Eisen is a Professor in the Institute of Neuroscience at the University of Oregon. She completed her PhD in neurobiology from Brandeis University where she worked  in the lab of Eve Marder, where she studied circuit neuromodulation in the stomatogastric ganglion. She later joined the laboratory of Dr. Monte Westerfield at the University of Oregon as his first post-doc, where she developed methods to label and track individual neuron progenitors in the zebrafish. She then was hired by the University of Oregon as faculty, and her lab has been focused on studying how neuronal diversity is generating during development, how these neuronal circuits are wired up and how host-associated microbiota and immune systems work together to influence the development of the nervous system. Dr. Eisen has authored over 150 publications, has been awarded the Gugenhein Memorial Foundation Fellowship, and is both a fellow of the Association for the Advancement of Science and the American Academy of the Arts & Sciences. 

Mar 2021 – Lori Zeltser & Alexandre Caron

The Chilling Side of Hunger

Dr. Zeltser is an Associate Professor in the Naomi Berrie Diabetes Center and the Department of Pathology and Cell Biology at Columbia University. she graduated from Princeton University and received her Ph.D. from The Rockefeller University. She continued her research training in developmental neurobiology and did her postdoctoral fellowship in the laboratories of Andrew Lumsden at Kings College London and Claudio Stern and Thomas Jessell at Columbia University. Currently, Her laboratory studies developmental influences on the formation and function of neuronal circuits regulating food intake and body weight, they explore how developmental influences exert lasting impacts on body weight regulation. 

Dr. Caron is an Assistant Professor at Laval University. He completed his PhD at Laval University with Drs. Denis Richard & Dr. Mathieu Laplante where he studied how an mTOR interacfting protein was involved in energy balance. He completed his post-doc at UTSW with Dr. Joel Elmquist, where he focused his efforts into studying how leptin is produced and where it functions through pharmacogenetics and transgenic approaches. His lab’s current goals are to understand the mechanisms by which the brain controls energy metabolism and develop pharmacological strategies to treat metabolic diseases and disorders.

Feb 2021 – Nicholas Betley & Daniel Drucker

Sensing Nutrients, Secreting Peptides

Dr. Betley received his Ph.D.,from  Columbia University, in 2010, where he worked with Thomas Jessell and investigated the developmental programs that determine synaptic partners during circuit formation. For his post doc he worked in Janelia Research Campus with Scott Sternson where they examined the structure and function of neural circuits that influence feeding behaviors.currently he is an Assistant Professor of Biology at the University of Pennsylvania. His lab is interested in understanding how the brain processes information from the external world to facilitate appropriate behavioral responses that are necessary for survival. 

Dr. Drucker is an Endocrinologist and Professor of Medicine in the Division of Endocrinology at the University or Toronto. He was trained in Internal Medicine and Endocrinology at the Johns Hopkins Hospital in Baltimore and the Toronto General Hospital, University of Toronto and completed a research fellowship in Molecular Endocrinology (1984-87) at the Massachusetts General Hospital. He has conducted pioneering work that has furthered our understanding of glucagon and GLP-1 and has authored several hundred publications, and issued 33 US patents covering various novel therapeutic aspects of peptide hormone action.

Episode 18: Our Greatest Challenge

Peter 0:13
Hi, and welcome back to the Gastronauts Podcast. My name is Peter and I’ll be your host. As many of you know, here at Gastronauts, we are committed to exploring communication throughout the body, with a particular focus on the crosstalk between gut and brain. We invite speakers across the globe to share both their research and their life journeys. So come join me as we explore the steps that go into shaping a scientist on the Gastronauts Podcast.

Today, we have a panel of four incredible rising stars in their respective fields. Dr. Kara Marshall is a postdoctoral fellow at Scripps Research in San Diego, California. She studies the nerves that control our bladder. And recently she found out that Piezo2, a molecular channel that senses mechanical forces, in fact works to control our peeing.

Dr. Kara Marshall 1:23
Thanks.

Peter 1:24
Dr. Dafni Hadjieconomou is a postdoctoral fellow at the Imperial College of London. She studies how neural circuits in the gut of a fly, or these enteric neurons, are altered during pregnancy. And she has found that these enteric neurons are key to increasing food intake of the mother and enhancing reproductive success.

Dr. Dafni Hadjieconomou 1:45
Thank you.

Peter 1:46
Dr. Marcelo Zimmer is a postdoctoral fellow at Yale and the Federal University of Rio. He studies how certain neurons in the brain of a neonatal mouse respond to maternal separation. Activation of these neurons induces ultrasonic vocalizations or USVs to encourage the mother to return to the pup, so she can continue providing care.

Dr. Marcelo Zimmer 2:08
Thank you.

Peter 2:09
And lastly, Dr. Yuuki Obata, is a postdoctoral fellow at the Crick Institute of London. He studies how bacteria in our gut talk to neurons in our gut to change intestinal motility and control the rate at which food moves through our intestinal tract.

Dr. Yuuki Obata 2:25
Thank you.

Peter 2:26
Science is a global endeavor, and we can tell from this conference with people calling in from all over the world. It’s really great seeing so many excited and engaged scientists, but it has to start small- from the groups with the people that you work with, with the mentorship that you provide different people who are just, you know, trying their first time in science. Now that you all are transitioning from the postdoc to perhaps an independent investigator, what mentoring principles Do you guys hold? Or what are you looking for in a trainee?

Dr. Kara Marshall 2:56
I mean, I’ll start I mean, I’m not a PI yet. But I actually think about it a lot. Because this is the huge jump that we have to make, right? We go from being bench scientists to all of a sudden being mentors, and it’s a completely different job. So I think about it a lot now to be like, how can I prepare and do a good job. And I think that one of the things that I’ve learned the most is that, you know, just like anything else, it is a skill. And unfortunately, I think a lot of people don’t consider that as you know, a skill that they can build and should try to build. And like, there is known information out there about how to be a good manager, and scientists are not concerned with that, right? Because we’re all excited about the science. And so we all focus on just like let’s get the science done. But um, yeah, as a PI, like, you have to manage people, that’s kind of your number one job. And so I think that, you know, I was talking to someone not too long ago about how she actually just hired someone in the business world to teach her how to hire people, and how to manage people, because it’s like, these are not unknown things, and scientists just kind of like, wing it, you know, and ends up being it ends up making for really, sometimes unprofessional environments, and then also environments where really, people aren’t doing their best science because they don’t feel like they’re being managed appropriately. And so I don’t know, I guess just having a growth mindset. That’s kind of cheesy, but it’s true, right? Like, you can learn these things like there’s, you know, data out there. And so trying to actually just learn the skills that are needed to manage people, I think, and just listening to people and actually really listening to what each individual needs and not just trying to one, one fits all solution. That’s my goal.

Dr. Dafni Hadjieconomou 4:29
Yeah, I would really also second that, I guess, for me, with a little bit of mentorship that I have given and what I have experienced, I think this the you should never think that one fits all is the take home message for me. You know, because I have also tried to be the mentor I wanted but this doesn’t always work. So I guess it’s going to be a lot of trial and error and there will be biases, you know, for for the mentor you wanted to have always or you had and you really loved or you had an you really hated. And I guess this is why what you’re saying care there is is important, perhaps we have to really work on this as a muscle that has to grow actively. And I guess also, again, get information as we do with everything else get information from people that have done it a while back. And we respect for instance, I guess this is how I plan to do it.

Dr. Marcelo Zimmer 5:25
Yeah, I definitely agree with Dafni, I think we need to learn from people who are already in the lab mentoring people, because as Kara said, we don’t know how to manage people, and then we suddenly we are being mentored to mentor people. So it’s a rapid transition. As a mentor, if I’ll be a mentor, one day, I’ll try to use my experience during my PhD, to do the same that I that I received while I was a practitioner to the students. And I think one of the best ways to do science is being always highly motivated. You need to motivate your students, we know that motivation plays a critical role in continuing science, because we’re going to fail all the time, failure will be a part of the process during our studies. So I think having a highly motivated mentor, they allow us to do anything that you wanted. I think that is the key, in my opinion.

Dr. Yuuki Obata 6:18
Yeah, I think I was very lucky to have great mentors. So what I learn from them in my future career. And also I have experience to teach some students in the lab, and they’re also great, and they really like science and think about trying to addressing the question not just for the job. So then the very good relationship was built. So yeah, that’s I think that depends on the motivation, the science and yeah.

Peter 7:02
We have a question from Lihua.

Audience 7:04
Dr. Zimmer, my question is: early life isolation that used in your model, your mouse model have been known to induce irritable bowel syndrome in the mouse. I’m just conscious curious, like, whether you finding has anything that related to the symptoms that developed in mouse models later in their life, like, increase of visceral sensitivity, and difference in the enteric motility and whether you’re finding will have anything connection to that

Dr. Marcelo Zimmer 7:39
Thanks for the great question. It’s something that people usually ask for us, if you follow the facts of the material separation later in life, and we never follow actually. So I don’t know. I don’t know if they actually they could be contributing for the development of the irritable bowel syndrome, but it’s definitely like at a very important question to try to evaluate the future for sure. Thanks for the question.

Peter 8:04
Next, we have Julia Davis.

Audience 8:06
I’m calling him from Boston. And I just had kind of like a more general question. Earlier this week, I was just looking at some literature and kind of like the gut brain axis and its relationship with neuro-inflammation. And I was wondering, like, if any of you kind of have thoughts on that, or like the mechanisms for how that might influence other disorders like delirium, or Alzheimer’s disease, which are often linked to neuro inflammation, and just kind of like, if you think that there is kind of value in going down that path, and seeing if there’s the microbiome does can play a role in our understanding of those diseases that are still kind of a little bit unclear.

Dr. Dafni Hadjieconomou 8:41
I think it’s pretty exciting. And I guess we don’t have the tools perhaps, or the understanding yet on how this works exactly. But, you know, and this is what I sort of wanted to put out there with my introductory bit that is so complicated, because we just beginning to understand that this microbiome does a lot of very different things. And, you know, Yuuki presented one of these aspects, but I guess it’s out there that this is all regulated and there is a link for sure with with the brain, and then all of these disorders could be coming from the microbiome, and then they are linked directly to the brain or their local inflammation in the gut that then link looks back to the brain. And I guess all of them could have a little bit of that. And something we don’t quite understand yet. But sure, sure. Is it an exciting way forward to think about that?

Audience 9:43
Hey, everyone, my name is Maya Kaelberer. I’m at Duke University. So my question is actually for Dafni, and Yuuki: how’s the microbiome changing during pregnancy? And is it known if these changes are actually affected some of the food intake right so I’m assuming that pregnancy does a lot to the body. I’m just wondering does it change the microbiome? And can you actually change your food intake that way?

Dr. Dafni Hadjieconomou 10:06
Thank you. I think I’m gonna let Yuuki go first. I’m not a microbiome expert.

Dr. Yuuki Obata 10:13
I’m not sure about this. And we know maternal microbiota is very important for the development of the immune system and nervous system have in the offspring animal. But in this case, I’m not sure how pregnancy affected it. I can imagine there are many changes to hormonal change can affect the microbiome, but I don’t know.

Dr. Dafni Hadjieconomou 10:33
And if we take it back to the fly, I guess there there are differences in general, with the microbiome and the colonization, and so on, as surely when flies lay eggs, they do also lay a bit of anti-microbials. So there might be changes. Sure. We don’t know if these do affect the way the flies eat? Not to my knowledge. I don’t know that. But yeah, very interesting question, Maya, for sure.

Peter 11:08
Yeah, I think it’s a really great question. And it made me think of, I guess, technological developments, and how we think about technology changing over time, and a lot of our studies are done really at a specific time point, or at a specific location, right? How do you expect your findings to translate across time or at different stages during development? I think each one of our talks today had a little bit of this theme, right? With Marcelo’s Agrp neurons having a different function early on in life. Dafni during reproduction, you have, you know, this innervation that has a differential effect. And Kara, right, when you mentioned, specifically like these Piezo2 neurons and piezo and urinary issues happened primarily when we’re older. So I was curious as to, just to reiterate, like how you expect the findings that you have to translate across different times? Or is this something that you’re interested in moving forward?

Dr. Dafni Hadjieconomou 11:57
Yeah, absolutely. I think, you know, this audience is already already unique, that, you know, we do think of other bits of the other organs, not only one, like people normally really focus on one neuron in the brain or one year, in their favorite place, or, and here, we’re talking about inter organ signaling. But I think also, yes, absolutely. For me, the timing is a very important element, because we you look at this ms neuron that I described, and it’s very different after mating, animated female. And I have also seen that it’s, it’s quite different after different food in food to being presented with different dietary challenges, let’s say. So this is also what I plan to do, I plan to see what happens in different challenges internally, but also in different times. So developmental is one thing, and how that shapes its function in the adult, for instance, because now what I presented, you were specifically adult neurons, right, that were manipulated for a few hours in the adult body. And that’s the beauty again, of the fly. But you can do the manipulation the other way around and look later on what happens. So for me, absolutely.

Dr. Marcelo Zimmer 13:14
I think that one of the biggest reasons that I’m doing this research in infants is trying to understand how the new secrets which neural secrets involve, and which neural secrets regulating behavior, because what we know from the literature is that any type of early life stress in an infant, and we’re talking about many types of mammals, including humans, leads to long term consequences. So if you at least start to tracking which are the newest they are, they are sensitive, when the animals are isolated with animals are exposed by like stress, we can actually benefit us understand if the neighbors were involved in this long term consequences that we see when we isolate all the animal is exposed to like stress.

Dr. Yuuki Obata 13:58
Yes, time is a very important factor for for our system as well. Actually, we are recently interested in the effects of the time of the day in the in the physiology of the enteric nervous system. As you can imagine, it’s it has a circadian rhythm in the activity of chronic peristalsis. And also, the number and composition of microbiota shows circadian rhythm as well. So we we are actually interested in how changing their time affect the physiology. Of course, we also are interested in the developmental time period or embryonic stage. This is a very important topic to study.

Dr. Kara Marshall 14:44
Yeah, I kind of touched on it. I totally agree that given the role of aging and kind of how aging ends up corresponding with a lot of issues in the urinary tract, it’ll be interesting to see how these circuits change how the sensors change, and then Development here. I mean, both sides of the equation are really fascinating.

Audience 15:02
Hi, hello, I’m Elaine Snell, I’m from London, does Piezo2 naturally diminish with age? And in which case, does that explain the high rate of urinary dysfunction in people of an older age group? And would that be or is it already a target for for treatment or strategy for treatment to kind of replace that if that’s possible?

Dr. Kara Marshall 15:25
Excellent question. And it’s something that I can’t answer directly, because we don’t know if the protein expression changes during age in the system. But I’ll answer it from the perspective of what we know about the skin because we know a lot more about touch receptors in the skin, which are also mechano-sensitive. And we do know that with age people do lose these sensory neurons. So your innervation, density goes down, and you become less touch sensitive. And so it’s very possible that this happens internally as well. And again, I think that this is an entire area that could be really interesting to understand how internal innovation changes with age, and maybe it’s diminished in the same way that our skin innovation has diminished. And all of the sequela that come after that, right? You know, neuropathy, diabetic neuropathy, which of course, diabetes is very common, and that leads to degeneration of some of these, some of these innervation. And it could have, you know, similar effects in the skin as it does inside, so you might get all of the reflexes, all of the sensing, if that’s gone, you know, that could absolutely cause dysfunction. And so I don’t know yet, but there’s definitely a precedent for that in other organs. So it’d be interesting to see. And then as far as therapeutics, you know, I’m a big believer and understanding the basic science and molecules of how things work, give us targets. Right now, we don’t have good pharmacological tools to target this ion channel, in particular. It’s proving to be actually quite difficult, because unlike a lot of other ion channels, these respond to tension in the membrane. And so how do you make a drug that targets that- it’s not clear that we’re going to have great like a lock and key mechanism where we can get something to bind. And so that hasn’t been very easy to find so far. In the future, though, it would be wonderful if it could, because I sort of touched on in the beginning that this, this protein is involved in so many different sensory functions. And so it would be great to have a pharmacological tool. But you know, if not pharmacological, you know, maybe there’ll be something else, some sort of genetic tool, or even estimate stimulation protocols, or something that we could do to help in the future. It’d be really interesting.

Peter 17:21
Next, we have a question from Valentina.

Audience 17:24
I’m calling in from Boston. And I have a question for Kara. I was wondering if you looked at the role of sex hormones in your model. And if you think, or if you observed any differences in your knockouts between males and females. I guess I’m just wondering if sex hormones might potentially regulate Piezo2 and these different patterns for urination?

Dr. Kara Marshall 17:47
Yeah, that’s interesting. So I haven’t looked at this at all. But it’s an interesting question, because we do know that some of these lower urinary tract pathologies are very different between men and women in terms of what kinds of pathologies they get, and how they manifest. And part of this is simply anatomical, males have much longer urethra. So they’re less prone to say UTIs but then there are other problems that come with having a prostate. And so part of these anatomical differences kind of designate what the pathologies are later in life. So I haven’t looked at sex hormones in particular, but it’s also possible that kind of overlaid on top of the anatomy has some role. But I don’t know the answer to that yet. I will say that I did do full cohorts of males and females in all of my studies. And to the extent to which the responses are slightly different because of the anatomy. All of the other phenotypes were exactly the same. So I saw the same deficits in males and females, they saw the same remodeling. But again, you know, males, because they have, especially in mice, their ureters are so small and so long, that the coordination is particularly important for them to go. So I think the remodeling was maybe worse for them. But overall, it seemed like the result was the same in males and females. Thanks for the question.

Peter 18:57
Yeah, that’s interesting, this sex difference question reminded me of some of the things that Dafni talked about with the MS neurons. And I was wondering, do the sensory neurons of urinary control change during pregnancy? Like what are the parallels between the enteric nervous system and the bladder?

Dr. Kara Marshall 19:11
Yeah, I’d say that it’s all open. You know, I don’t know, I hadn’t really considered looking during pregnancy. But of course, that is a- that is a time of like, massive change. So it’d be interesting to know if some of the innovation changes to I don’t know.

Dr. Dafni Hadjieconomou 19:25
Yeah, I don’t know. This is why I thought, you know, it would be very interesting to see if the neurons change or the epithelium changes with both of them, and what happens at the molecular level, because, you know, somehow this body needs to cope. it undergoes under increasing pressure. And I guess in the mouse model, you might have more or less pups, and that also might change. So I think it’s very exciting to just have a look. Yeah, and I would imagine that there are changes, but then yeah.

Dr. Kara Marshall 19:59
I also wonder how different it is between mice and humans, given that humans are upright, and so much of that gravitational pull has a huge effect. And in mice, I wonder if I’m being this direction means that that is different. And you know, the the two horn of the uterus, maybe they actually are spared some of the issues that humans go through. I don’t know, though, be interesting to find out.

Peter 20:21
This is really interesting. Moving on, we have another question for Dafni. So the fly mid gut is like the primary site for food digestion & absorption, what is known about neuronal innervation in the fly mid gut? How are the enteric neurons affecting intestinal motility? absorption?

Dr. Dafni Hadjieconomou 20:40
Yeah, thank you. So not a lot was known. And the truth is that not a lot is known. So in fact, Irine’s lab really did bring home this. So she was one of the founders, I guess, in it, and there are enteric neurons and the fly. And the paper, the first paper of the lab described some of this innovation in our paper, the recent paper also gives a bit more information about the integration of the medical and especially the anteromedial, which is, I guess the question goes for that, where a lot of the digestion is happening now for the function. So we do know, for specific lineages, some of the aspects of the function that do go to the mid gut, and the neurons that I talked about today go to the mid gut, as well as the crop. And now for peristalsis, for the midgut. Specifically, I guess we don’t know exactly how they. So their motor, so the motor output is for specific types of neurons. If you talk completely paralyzed, of course, the gut. Yeah, there is a problem. But it’s just the beginning of this. So similar to the mammalian lineages, we did not we didn’t know so much about them, I guess, what is nice is that we can manipulate small subsystems of them and uncover what their function is.

Peter 22:05
Great- I actually had like a relatively broad question for all of you is really interesting seeing the different model systems that you all use. Marcelo, you mentioned that you’re planning to do some future work in guinea pigs, Dafni, you’ve been working flies; Kara, you’ve done some human studies, and Yuuki, you’re doing work in a nice. So I was wondering, how do you choose which animal system to use? And then in your future work do you plan on continuing to use the same animal models? Are you planning to diversify what systems you’re going to be studying?

Dr. Kara Marshall 22:32
I will say that it was actually a really fortunate thing that we were able to include the humans in the study with the mechanistic mouse models. And I think there was a bit of luck there, I mean, to have this group of patients was, we were incredibly fortunate because of course, you don’t always get that with any particular gene that you’re studying. So I would love to do more of that in the future. But I think it it sort of depends on, you know, wonderful collaborators, being open to open to working with us. And I think that that’s a general lesson in science, that if people are open to collaborating, especially across disciplines, like with clinicians, because of course, the science is very different, that the story becomes so much stronger. And so I mean, I would love it, if that could happen in the future again.

Dr. Dafni Hadjieconomou 23:13
I do plan to work on flies and, and actually collaborate or anything else. So my drive is really coming from basic discovery in basic science. So I think the fly is a powerful model for understanding genetics, and really basic mechanisms. And then the conservation of this, you know, other people that I can collaborate with can do in, in higher mammalian systems, let’s say that being the mouse or humans, for instance, I will be very excited to work with people along along the way. But my drive is really this basic mechanisms, and I plan to work on flies for the rest of it.

Dr. Marcelo Zimmer 23:57
I think, really the purpose of our long term goals. But I think as a scientist, we always try to contribute to the well being of the human being and to humans. But the reason I choose to move towards minipigs is that I’m really interested interested in the infant’s perspective of interaction with the mother. Whereas we know a lot of researchers in a lot of studies doing the maternal behavior in mice, right. So we don’t know much about how the infant’s they communicate how they how they interact the mother, most likely most because these infants they are born in a three show state, so they are really mature. So we cannot really evaluate the behavior of the infants during this first few days of life. Whereas the green epic the infant is born in precocious states, so the animals are much more active, much more mature. So using this animal model, I think we are able to at least understand better when do me think about your secrets that are involved in the infant direction to the mother.

Dr. Yuuki Obata 24:57
So for me, the reason I’m here using the mouse, so it’s just it’s very, very well organized, it’s very established model. But I’m also interested in the other other models, including a human, or even Hydra they, or zebrafish, because each each model has on advantage and disadvantage, a bad combination these studies helps us to understand different aspects of physiology by using different techniques.

Peter 25:28
Yeah, it’s really great to hear all of your perspectives on the pros and cons of different model systems, how sometimes it’s due to collaboration has sometimes it’s due to chance.

Audience 25:38
Hello, I’m yeah, I’m Alistair McDonald. And I’m calling from Exeter in the UK. And my question is for Dr. Marshall, I’m interested to know how much of the Piezo2 pressure sensing is, is mediating intrinsic kind of bladder or spinal to bladder versus integrating top down control from the brain. So you have some looks like full urination in the middle of the cage. So maybe properly initiated, but just at the wrong point, how much of that sensory detection is useful for the brain?

Dr. Kara Marshall 26:09
Yeah, so all of the functions I was showing with regard to cystometry and the urethral reflexes, these would be spinal reflexes, right? So these are mediated by spinal pathways. And, you know, we think the sensory neurons, of course, are directly conveying information, the bladder goes to the urethra, and the urethra actually goes to the bladder. So you know, you want when your bladder is ready to contract, you want it to contract against a relaxed urethra. And then similarly, when your rethrow has fluid flow go through, it sends signals back to increase bladder contraction. So these kind of are classical reflexes that have been defined for a while. So we think that definitely Piezo2 sensory neurons are mediating the initiation of these reflexes. But we haven’t looked at all as to you know, how this sensory information is integrated in Barrington’s nucleus, which is the nucleus that controls top down urination. And I’m so glad you brought it up, because it is really important. And in fact, people who study urination, primarily study these brain mechanisms that are critical for release of urination and of course, in humans and other animals. We have tight control over this and we don’t, you know, we only are supposed to go at appropriate times. And this is very important. And so I don’t know yet how Barrington’s integrates this information, but certainly it must right it It knows when your bladders full, and otherwise you don’t have that kind of urge. So yeah, I think it’d be really interesting to understand in the future, what those neurons are sensing.

Peter 27:51
We have a question from Jorge Villalobos.

Audience 27:54
Hey, I’m Jorge. I’m calling from Duke University. And I have a question for Dr. Zimmer. So Dr. Zimmer, what would happen if you play a recording of ultrasonic vocalizations on one side, then if you have a pup on the other side, would the ultrasonic vocalization would be like a stronger stimuli for the dam to prefer that side? Or would the olfactory cues from the pump would be a stronger signal and then the mother would go to the other side?

Dr. Marcelo Zimmer 28:23
Yeah, that’s a great question. We’ve never done this type of experiment, we try to evaluate whether only playing record user playback system in which we would play the record off of error mode in which we activate the newest compared to animal that is a control animal to see the model prefer one side over the other. And we are not capable of having like a final result, we realize that odor cues are super important. So not only visual cues, because once the mother realizes there is no neonates that are there she stopped, she stopped directing, but there are so we never done that. But if I have to guess I would say the daughter queues and this stage, they will play a higher role will be more important for a preference of the monitors, either the odor queues or the auditory cues.

Peter 29:14
Thank you. And we have another question from Amy Shepard.

Audience 29:18
Yeah, hi, I’m calling from Boston. And my question is for doctors around the USVs. I was wondering if not only does the number of calls change, but just the quality or complexity of those calls change. I’m only really familiar about USVs in adults, which I know have, you know, like a lot of variation. I wonder if you looked at that and those parts as well.

Dr. Marcelo Zimmer 29:38
That is a great question. Yes, we look at and indeed change change the part of the cause the animals they elicit different types of syllables. So in neonates, the list of 11 types of syllables that we know and when we quantify the number of vocalizations, in which syllables we find their activation of these neurons, the indeed increase some of the syllables One that we found was a channel was it was a charity organization. So we are trying to identify whether this has any meaning for the mother and look and talk about the spectral temporal features of the vocalizations, it does have a decrease in the duration, it seems to lead to change the new frequency distribution. So, yes, there’s a change.

Peter 30:20
Thanks for the question on communication, like USVs are ways neonates communicate, and I was wondering, you know, broadly about communication. We don’t communicate with USVs. So I was wondering, how do you think about communicating your work to fields very disparate from your own? How do you think about communicating to form collaborations and communication in general to inform the general public?

Dr. Marcelo Zimmer 30:42
Yeah, that’s not an easy question. What we can try to communicate the general public is that we see the vocalizations of the infants as a form of crying of the animals. So the way that we try to communicate that we are trying to identify one of the most innate behavior that we see not only in mice, but also in humans, which is a crying behavior. So this is the way that we try to communicate for general public our findings.

Dr. Kara Marshall 31:07
It’s kind of weird to study your nation. And I think as a neuroscientist when people say, Oh, you do neuroscience, what do you study? It’s, it’s something that kind of takes people back when you’re like, oh, urination. And it’s because I think societally, it’s not something people talk about, like when again, I was really stunned by the epidemiology. And you can pretty much bet if you’re talking to an older person, they’ve had some issue with their urinary tract. And so I think it’s actually, it’s been really neat to see that by studying these kind of basic functions, it opens the public up to talk about things that maybe they wouldn’t normally talk about, or even honestly, for adults to know that they’re not alone, that this is actually really common, and that they should seek out help for some of these issues, when you know, it’s sort of not not discussed very often. So I would say that, in some ways, urination is great and easy, because everyone does it and really connects to it because it’s a normal part of their lives, and lots of things go wrong. But on the broader scale, I think, for so long, especially in touch research, and like doing very basic science research about ion channels and stuff, it felt disconnected from the public. And I think that what’s been nice is kind of being able to really teach people the importance of just basic science. And I’m sure Dafni has strong feelings about this working in flies, because, I mean, I see the gorgeous, like, whole gut images, like there’s so much you can do in flies. And I think that, you know, conveying to the public that like figuring out these really fundamental questions, like answering fundamental questions is just about, like, how does this system work, even if it’s in, you know, a simpler model organism or something is really just like an important foundation. And I think that it is so critical to convey to the public, like basic science research is how we get to this translational stuff. And, you know, you don’t always know where that will come from. So you have to have a really broad foundation of basic science research in flies, and then, you know, mice.

Dr. Dafni Hadjieconomou 32:59
I do feel like that. And I think, just being in the business for a bit longer, you just sort of know, to filter down the information that you give to people, you know, people just ask yourself, what, what excites you and what are you working on? And you can start by saying, Hey, you know, I worked to understand how the brain works. And so you know, of course, everybody’s kind of interested in the brain. And then people are interested to find out that their neurons in your gut, which you know, and it’s a surprise to a lot of people still and I guess, then if you talk to them and bring it home, that if something doesn’t go really well, with that, you you might have an eating disorder, let’s say so I think you always have to link things, as Kara said, as, for instance, with the older people with something they have experienced and remove the jargon as much as possible. It’s not very easy. I think, if you just get better with the more you do it.

Dr. Yuuki Obata 33:55
Yeah, this is very difficult. But yeah, very important to communicate with the public. So in my experience, I have contributed to make a documentary film about gut physiology in collaboration with TV programs. So they they’re professionals. So we don’t we just provided the concept and the beautiful image of the gut. So that was, that did work very well, in terms of the delivering the message to many people.

Peter 34:24
Just speaking of like, things in the public. One of the things really just coming up to public perception now is the importance of science with the global pandemic that we’re having and coronavirus. What do you think the biggest hurdle or issue that our generation of scientists is up against?

Dr. Marcelo Zimmer 34:41
So I think we are not trained to communicate, so we don’t know how to communicate why we’re doing so that’s why I think we have this, this, this difficulty to talk to people. I mean, we don’t have any training to communicate what we’re doing to show the importance of why we’re doing. I would say for you Peter, it really depends well where you are as well, because I can I can say right now we have the opposite. People still don’t believe in science even more right now, because we have people that don’t think the vaccine is like this the cure for the COVID. So we have two problems in my vision, the first that we don’t know how to communicate. And there’s also political views about science, depending on the country, where you are.

Dr. Kara Marshall 35:20
Yeah, I agree. I mean, I’d say that I feel like in the US, politicians have been pretty good about like, continuing to fund the NIH, for example, even though there might be anti-science rhetoric in general, they kind of come through with some funding. But we need to be better not only about communicating the excitement of science, but just like how beneficial it is, like, I think these advances are so slow, you know, what’s coming on the market now might have been researched 10 years ago, or 15 years ago. And so it’s hard for a person and this is especially true in the private sector to look at this and say, Oh, you know, what you’re doing now is going to definitely economically benefit me and benefit humans. And so I think like, having a better narrative around these processes, and how they are slow, and it takes kind of people coming at questions from all different angles, which takes a lot of money. And I think that showing people that output and like the Human Genome Project was this moonshot. And it was it worked. And it actually like, has generated so much value, not only economically, but also just for knowledges sake, I don’t know, I think there’s like the two pronged argument could be made. So maybe scientists need to be better about communicating that.

Dr. Dafni Hadjieconomou 36:27
Yeah, absolutely. I think, you know, communication is a big thing. But I guess we’re also facing, perhaps an economic crisis I had, and that is going to impact science for sure. Across the board, so some countries will be more or less affected, I guess. So I guess this is where somehow we have to come together. And for more collaborations, perhaps and, and, you know, perhaps think of different ways of doing science, which is very hard, because careers are, you know, need to still be shaped. And it’s a it’s a hard one. But I guess you know, our generation could be perhaps more open. I don’t know, it’s a hard one. I think if I have to just find one that is going to be the most difficult hurdle to overcome. For our generation of scientists, I guess we are quite a lot at the moment, and very excited and the funds are might run thin for a wide base, I mean, or not, we’ll see.

Dr. Kara Marshall 37:27
I was just noticing someone asked about diversity and inclusion. And I was gonna say that one of the plans or hopes that I have in the future is, you know, of course, to have a really inclusive and diverse environment. But I think one of the ways to do this is really make sure that a broad range of undergrads get a chance to be in love. Because I think that’s the time at which most of us get our first experience with research. Like, I didn’t know anything about being a scientist, when I was an undergrad. I mean, I liked science. But I think that just making sure that a broad range of undergraduates that you know, may or may not have been exposed to science at all, like have the chance to go through lab. And what that can do is really allow us to practice mentorship at all the different levels, right, if you have grad students, mentoring undergrads and postdocs, mentoring graduate students, and like making sure that not only is everyone welcome in lab, but also people practice mentoring a diverse set of you know, others, right, and it’ll, you know, maybe people when they’re undergrads decide they don’t like it. But at the very least giving that opportunity and making sure that people from a broad range of backgrounds have the chance to access that is good. The other thing is outreach, I think is really fun. And we had talked about communication. But outreach to local schools is something I’ve always done wherever I am. And that’s also a really great way to introduce kids to the idea that scientists are real people. And it’s a manageable, fun career that you can actually pursue. And it’s not, I think it feels very kind of elitist if you’re not, you know, introduced to a scientist or whatever. So I think that encouraging communication, encouraging your lab members to seek out events where you go to schools and communicate science is a really good opportunity to both increase diversity and inclusion, but also to train people on communication and mentorship. So it’s like two birds with one stone.

Peter 39:07
Yeah, that’s really great. I think that question was from Yeka Aponte. I don’t know if you had a follow up.

Audience 39:12
Yes. I’m very delighted to be here today. I mean, thank you, Diego for inviting me. So I’m Yeka Aponte. I’m a tenure track investigator at the NIH. And Kara, your answer was a stellar because it’s about time that you know, especially when we think about gender, and we think about diversity & inclusion, that’s what he makes us stronger. And I think that we all have to when to reach, you know, the PI level to feel that we have a voice, you know, and that’s something that as you guys all said, no one teaches us how to be a manager we have to learn by doing. And I think that that’s kind of challenging. The other thing is that I recently became the director of the diversity and inclusion at the NIH, NIDA. And, and I think the one of the hardest and more challenging things is that, you know, expectations are really high when we join a lab. Interns, summer students, you know, and you have to understand when you have these kids that come from underrepresented backgrounds, they didn’t have the same privilege that most of us had, and the same training. So you have to put an effort to really, really get these kids to that level. And as Kara very nicely stated it, you have to start from like the undergrad level. I mean, if it were up to me, I would start, you know, for like, elementary school, but at least we have to start somewhere. And I think that this is the advice that I give all the investigators that you know, you have to be patient, you have to understand that perhaps in the first year, you’re going to want to get any data from that student, but the reward that you’re going to get one, that kid that perhaps is the first generation going to high school and college came out of your lab, you will feel so proud. I said, that’s my child, you know, that kid became a doctor because of me, because the training in my lab, so on a team that, you know, it’s about time that we educate ourselves about our conscious and unconscious biases, because we all have them, even if we don’t know. And, you know, this is something that, you know, I tell my lab members, we have to stop being bystanders, and you know, speak out & loud. I mean, I’m sure you’re all aware about this horrible paper that came out two weeks ago, and how female scientists not being good mentors, you know, I mean, on top of dealing with my background as diverse, I also have to deal with my agenda just to show people that yes, I can be a good mentor. It has nothing to do with my gender. So yeah, those are the comments that I just wanted to ask. But thank you, Kara, for just stating this at the level of you know, the trainees. So it was really enlightening for me to hear that.

Peter 41:37
Yeah, I don’t know if there’s any better way to close than that. I feel very empowered. I feel like we have to keep pushing the ball forward. We have to continue advancing science. And I really wanted to thank everyone here for coming to this Gastronauts Bite Size Summit. We really enjoyed your presence and we really valued your opinion. Thank you all so much for listening! Science is all about this open communication and how we can continue to advance it. If you can think of any other ways for how Gastronauts can improve, please feel free to reach out to us. If you feel like you’ve got something from this today, we’d love if you’d share this with a friend or a colleague and just get more people in the know-how about Gastronauts and about science. Thank you so much for joining us and thanks so much to our speakers.

Peter 42:48
Thank you all so much for listening and we’ll see you on our next episode. For more of our content, you can follow us on Twitter @gutbrains or visit our website at thinkgastronauts.com. The Gastronauts Podcast would be impossible without our incredible team. Meredith Schmehl is our producer and theme music composer, and special thanks to the founders of Gastronauts: Dr. Diego Bohórquez and the Bohórquez laboratory.