episode 1 edited

The Dendrites podcast aims to make scientific research accessible and enjoyable. They interview experts in the field to discuss their work, break down complex topics, and provide advice for students interested in research. Dr. Baptiste Lacoste, an associate professor at the University of Ottawa's Faculty of Medicine, is a guest on the podcast. His research focuses on neurovascular interactions, particularly how brain blood vessels support brain function and what happens when they are compromised. His lab explores topics such as vascular development, neurovascular injury (such as stroke), and neurovascular interactions in neurodevelopmental conditions like autism. Dr. Lacoste is passionate about finding ways to treat autism by addressing vascular defects, and his lab uses a variety of techniques, including imaging, behavior studies, molecular measurements, and RNA sequencing, to understand the disease at a holistic level. They have made progress in identifying molecular targets and cond Hello everyone and welcome to the Dendrites podcast. I'm Farnam Parcham and I also have Saeed as my co-host today. We are really excited for this podcast and we have an amazing guest with us, Dr. Lacoste. For those of you who are tuning for the first time, this podcast is a part of Dendrite Club at the University of Ottawa, where we aim to make scientific research approachable and fun. Each episode will sit down with a professor or a researcher to explore their work, break down complex topics and give students practical advice on how to get involved in the real world of the research and how to explore more options and more knowledge about research topics. Exactly. So now more about our guest today, Dr. Baptiste Lacoste is an associate professor at the University of Ottawa's Faculty of Medicine and a principal investigator at the Brain and Mind Research Institute. Dr. Lacoste is known for his pioneering research in neurovascular interactions, which looks at how the brain's blood vessels support brain function and what happens when they compromise from an early age. Awesome. I'm very excited. First of all, let's say hello to Dr. Lacoste. How are you doing? I'm great, Farnam. Thank you for having me on the podcast. Perfect. Thank you very much for coming and be as a guest of our podcast. I know you had a very busy schedule, and I know you have a seminar coming up in a week or so, right? Yeah, preparing for next week. Okay, cool. Awesome. Well, thank you very much for being here today. I just want to explore a little bit of the topics that you are working in your lab. Just give us a brief introduction to it, and what have you been working so far in your lab? Sure. Thank you for this question. If I summarize, we have three main themes in the lab, all around what you just mentioned, which is neurovascular biology. The first thing is to know how vessels in the brain develop, so how they form, before even knowing how they get compromised. This involves research on glial biology, because we look at astrocytes and their control of vascular development. Then the second big theme of the lab is neurovascular injury. We have studies on stroke, as you might have seen, and ischemic injury. I would say the main, the third but main theme of the lab is mixing this idea of vascular development with neurological disorders, and basically looking at neurovascular interactions in neurodevelopmental conditions, such as autism. These are the big avenues we have developed in the lab. Perfect. That is very interesting. You mentioned disorders. What kind of disorders specifically are we talking about here? The lab, since it started, so we started in 2016, has really taken a full spin on neurodevelopmental conditions. I know it's a vague word or expression. It englobes autism, per se, but we talk more about autism spectrum disorders, because it's a wide range of conditions. We also have expertise on Down syndrome, and another syndrome called Fragile X syndrome. More recently, we have obtained funding to look at the SynGAP1 deletion syndrome, which is another type of intellectual disability. You see that it's a vast amount of disorders, but we classify them in neurodevelopmental conditions. I just wanted to ask, because you've had an incredible academic journey from University of Bordeaux to then Montreal, McGill, Harvard, then University of Ottawa, what was the first time that you became interested in neurovascular interactions? How did the whole journey start? That's an interesting question. Very late. When I was in Bordeaux, as you as a young student, I was doing my undergrad studies, and mostly interested in neuroscience. I was fascinated by neurobiology, and I wanted to know how synapse works, how neurons communicate. This really was a passion. Then I started to do a master's study in Bordeaux, based on Parkinson's disease. It was neuroinflammation and Parkinson's disease. Then I wanted to do more about diseases of the brain. One of the things that young students should do is get away from their comfort zone and country, if they can, if it is affordable. I moved to Canada to do a PhD in the lab of a now passed away researcher who had a specialty in electron microscopy. He was studying the underpinnings of depression and mood disorders in terms of peptide trafficking of different receptors, which has nothing to do with the blood vessels. As you can see, I have a neuroscience background. I am more of a neuroanatomist, a morphologist rather than even a physiologist. When you want to become a professor, you appear to have a PhD, which is unfortunately not enough. You need to do a postdoctoral fellowship. I wanted to keep working on diseases. That is what I am interested in. I had this twist on neuroinflammation. I moved to the lab of Dr. Abis Hamel at McGill University at the Neurological Institute. She was working on Alzheimer's disease and neuroinflammation. It was perfect for me, so looking at glia and neuronal defects. She also had a PhD in the twist on the vasculature. She was looking at blood flow dysfunction in Alzheimer's mouse models. In that lab, I said, this is very interesting. I spent almost three years there. I wasn't enough. When I saw all these vessels degrading and losing their function, I asked myself, what about the other extreme of life? How do they develop from the get-go? I sent a few emails randomly. The first person who answered me was a PI from Harvard University, Changhua Gu, who at the time was a younger scientist looking for postdocs. She answered within 15 minutes, saying, I'm interested. Long story short, I went for an interview, made it, and then spent three and a half years looking at how vessels develop. Wow. That is… Then I come back and say, I'm going to do what I want. I took the disease, vasculature, development, and I decided to work on autism. Awesome. That's very cool. I'm sure throughout the whole experience, you had different passions and different interests. What is it that currently is your main passion and you're trying to find a solution or find the answer for that question specifically? What is it that keeps you awake in nights and mornings, I would say? Yes. At night, it becomes an obsession when you're already passionate. What is it that you're currently really interested in and trying to find an answer for? That's an excellent question. The word passion is actually well-chosen because you cannot be so much invested and committed in something you're not passionate for. My quest, I'm going to call it this way, is finding how you could treat autism by treating the vascular defects. The reason why it becomes more and more every day a passion is because we are finding the causes now of vascular deficits in autism, at least in mouse and cellular models. Recently, which is unpublished, we actually started to find a way to correct these deficits. We do now think about applications in the clinic. We are in the steps of finding the patents and wanting to move into the next steps. That's my passion. It's really helping patients and their families that suffer from autism from an out-of-the-box thinking perspective, which is through the vascular system. That is awesome. We just want to maybe dig deeper a little bit. What kind of techniques you are using in this particular research area? Give us some more, like if you want to put it in simple words, what is it that you are actually doing to find those patterns of autism? That's a great question. We might not have time to describe what are the models we use and how they were generated and how we model autism in mice. This is a long story. I can tell you we do a lot of things. My lab, I would say our lab, because it's a teamwork, not my thing. We work as a team. We are very multidisciplinary. It's not one technique, it's many techniques, from physiology to imaging to molecular measurements. We do a lot of macroscopy. We do a lot of electron macroscopy, so a very specific way to image. We do a lot of mouse behavior. We do RNA sequencing. We do measure metabolites, lipids in cells, in plasma samples. We do almost the whole spectrum of experiments you can think of from in vitro to in vivo in laboratory models. This is helping us to go deep in the science. That's what I want. I want a holistic view of a disease, but also a very thorough analysis at every level. Basically, that's the philosophy we have. How do you make the connection between all these different research areas? There must be this translation between all the behavior of the mouse model and what we see in vitro, and then from mouse to humans, obviously. Basically, the link between all these fascinating and different areas that you were talking about. That's a fantastic question, because this is our job, is making links. My lab is a little bit special, and I am a bit special. We start by very exploratory approaches, saying and even betting, oh, we're going to find something. Let's do all these links. We started by exploring and being sometimes lucky to find one path. Then we follow that path very deeply and with a lot of intensity. When I say RNA sequencing can lead us to a direct target, it's actually what's happening. You find some changes at the molecular level, and you say, oh, that's interesting. Let's follow up that track. Then you try to identify what molecule needs to be changed. You say, oh, that's a molecule that is found at a lower level than it should be in a normal situation. Then you say, oh, wait, what about we bring back that molecule? We do what we call a rescue experiment, and then we bring back some molecules, or we stimulate some pathways. It works in cells. Let's try to do it in a slice, and then let's try to do it in a brain organoid, and let's try to do it in mice. We are now at the level where we can say, by bringing back some ... I can't even tell you, because this is common knowledge now, but we can bring back some energy levels in the cells and make them function better. Now, the next step for us is trying in mice, and then look at behavior. If we can correct an autism-like behavior in mice using a molecule, when we say, well, we're going to try this in humans next. Of course, it goes through ethics, and then legal issues, and many things, but that's what that's. That's awesome, and we really look forward to a day that we can actually have those experiments in humans. Well, one specific key topics of your whole research and experience is blood-brain barriers. From what I understand is, basically, it's a security system for our brain to see what goes inside and outside. Basically, from what I understood is, it's keeping some molecules, or some, I don't know, some atoms outside and some inside. I'm just curious if you can maybe explain a little bit more about what blood-brain barriers is. Yeah, sure. It's a fascinating question and topic. Extremely big and comprehensive, so again, long story short. The vessels of the brain are very special. All what I told you about autism in our work is not really based on blood-brain barrier, but the blood-brain barrier, I'm going to call it BBB, because I'm French, it's very hard to pronounce. The BBB is associated with many conditions and many interesting phenomena. The vessels of the brain are very special in the way that, as opposed to vessels from kidney, or liver, or even the skin, they don't leak. Nothing can go through a vascular tree in the brain. Why? Because there are very specific properties that make them sealed. You have very specific junctions, you have very specific pathways, you have purposely lack of communication, or lack of transport, that makes these vessels a barrier. So the blood-to-brain barrier is made such that, as you said, toxic molecules won't go in the brain, because let's say you eat something toxic, you are exposed in your environment to something toxic, it's going to go in your bloodstream. The brain is protected against that. You have an inflammation, you have bacteria, it's protected against that, thanks to the brain vasculature. The liver, the vessels are in the liver, kidney, the vessels are completely open, everything that is in the blood will go in the organ, and the brain is very special in this way. So to go to disease, I can very shortly tell you multiple sclerosis, MS, is characterized in its first steps by an opening of the blood-brain barrier to immune cells that are going to go in the brain and destroy synapses and neurons, which is causing motor symptoms. Alzheimer's disease, one of the later stages of the disease, is an opening of the BBB, again, causing neuronal death through incoming of all these molecules that should not be in the brain. People are suggesting that autism is linked to BBB defects. We are on this path, too. It's very preliminary, but that's an opening field. So that's a concept that people are following. So can we now speak about endothelial cells in particular? What is the developmental aspects that might cause some defects, for example, that would link to autism or any other disorder? That's exactly what we're actually working on. So if I summarize what our lab is finding currently, these endothelial cells, so endothelium means an epithelium inside. Endo means inside, and thelium comes from epithelium. So it's like a very thin single layer of cells that form the tubing of these vessels. And many people think that this is like a tubing, you know, we are like the plumbers of the brain and we fix tubes, but these endothelial cells not only form a sealed tube, but also secrete a lot of things. There's a secret growth factor that can help neuronal development. So again, I could spend hours on this. So what we are currently finding in the lab is those cells don't function properly. They have a lack of energy that does not prevent them from being alive. So your vessels don't collapse. You don't have MRIGs in the brain, but they don't support the functions that are triggered by different stimuli. One of them is cerebral blood flow. We can talk about this, if you want, but when neuronal activity is increased, usually you have a corresponding increase in blood flow. The regulation of this process through neurotransmitter release in other cells implies an endothelial integrity. The endothelium needs to be functioning properly. So we are finding that this endothelium does not work properly. And we are finding that correcting this dysfunction helps in our at least in my senses. So then how do you screen for some, maybe proteins or genes that regulate activities of these cells? Or then maybe they might cause these cells to have defects, like ROCK2 maybe? Yeah, so ROCK2 is one of the things we worked on recently on a small paper we published recently. Even before ROCK2, I can go back to the ROCK study. The way we really discovered that this function of cells is having some screening tools in which you can isolate these cells from a brain, a mouse brain, and then you have a suspension of pure endothelial cells that you either look at gene expression or a protein expression and metabolite content, but also function in different assays. So we've seen that they have less of energy molecules such as ATP, you know, adenosine 3-phosphate. They process less of this, so they have less energy. They function better when we bring back ATP. So that's something we are currently working on. It's subject to an actually patent application and we disclose it in different seminars, so it's not a secret. About the ROCK2 involvement, it's very interesting because the mutation, particular mutation we are focusing on in the lab, which is a mutation commonly associated with autism in humans, causes an increase in ROCK2 activity, which is kind of, I'm going to say it in a simple speak way, toxic to the cells, in particular the endothelial cells. When you reduce ROCK2 expression and activity, it's good for the system. It's good for the endothelium. So what we did recently is take a mouse model of autism and cross it with another mouse that has low ROCK2 expression and it helped many things, behavior, so we could by reducing ROCK2 function, ROCK2 is nice as a form of rock and lime. By reducing ROCK2 levels, we could not fix but improve a lot of things in this mouse model, vascular function and behavior in mice. Speaking of improving the vascular function, I just want to explore more of the effects that would change that vascular function. I mean, you earlier mentioned about the plasticity of this whole system, so I'm just wondering if there's effects like aging or, I really love the, there's a phrase called use it or lose it, but I always thought it was more related to the neurons and now I'm seeing that there's also another whole word about the vascular part of it also. Why don't you let us know more about the things that can affect in case of the vascular aspect of the neurons and so on. Well, it's a very interesting question and it starts from birth. So, actually when I was at Harvard University, my theme of research was how sensory input, so environmental sensory input, shape brain vasculature. So, what I discovered at this time is if you remove sensory input and even input from the skin, so at the time we were working with whiskers in mice, if you remove the whiskers in mice and then you start to just wait and see how the vasculature develops, it develops less in the region that you associate it with, that specific part of the body. And we have different ways to cut this input. So, you know, so skin sensation is going to go to your spinal cord, is going to go to your brain stem, thalamus and cortex. We have different ways to interact with this pathway and when we cut input from different places, we could see that the vasculature was reduced. So, as you say, vascular system in the brain is plastic. It also depends on stimulation. So, you can already think that a young kid that lacks environmental stimulation will have a less developed vascular system which has long-term implications for neuronal function because the vascular system supports the vascular development and function on the long term. And then to answer kind of also the question on the other side of life, the plasticity goes the other way. I would say it's not really like if you don't use the vasculature, it disappears, but actually it needs maintenance. The blood brain barrier needs maintenance and if you see diseases like Parkinson's, MS, Alzheimer's disease, the aging of neuronal and glial systems affect the way the vasculature is maintained and then you can lose vascular integrity. If you lose blood flow, less blood is coming. So, we didn't touch upon this yet, but blood flow is the only way to bring oxygen to the brain. Blood flow is the only way to bring glucose to the brain, energy, food. So, if you lose that, you lose neuronal function. So, it's a vicious cycle that is unfortunately in place throughout the neuronal mass. Perfect. Well, there you go, folks. You heard it from Dr. Lakos himself. You got to really challenge yourself and as he mentioned earlier, try to really come out of your comfort zone to be able to maintain those vascular functions. So, what therapeutic pathways can we now think about? So, how can we maintain this, the health of the vascular, neurovascular system on both ends of developmental aspects, at the beginning of the life, the end of the life, and throughout? What can we do about it? Well, we just want to maybe know some practical advice for people who are getting older these days. Social media, chat GPT, we don't really get to use our brain. So, what are some practical advice that you can give? Yeah. So, I'll answer both questions at once. And then, I think both of what you just touched upon is very interesting. You have drugs that can help and you have behaviors that can help. Exactly. So, we are working on future drugs that can help to regenerate on the cellular function to support long-term neuronal function because we know now there is a crosstalk between these two. People are working on this actively. You can maintain BBB, double-layer integrity, through different molecules. And I'm not going to list them, which is not my exact field of expertise. But many companies invest billions of dollars in fixing the BBB or going through it because you need to go through the wall to deliver drugs to the brain. And unfortunately, the BBB is a limitation for drug delivery. So, this is a huge field of research. And we are actively involved in the autism field. So, give us 10 years, we'll give you an answer. Concerning the behavior, well, I would say not to kill all the companies that invest all the billions of dollars. One of the things that is so easy to do to target your blood vessel in a good way is exercise and a good diet. So, good practices in this life, diet, exercise, not becoming sedentary, moving. Some people cannot do exercise. All the people and all people with handicaps cannot go to the gym, but at least they can move a little bit. A constant movement will trigger a lot of things in your brain, including secretion of different molecules that will fix your blood vessels. And the blood vessels are the first line of defense for the brain. So, a lot of scientists now agree that even from our life, constant exercise and mix with a healthy diet is going to be helping your blood vessels, hence helping in your own health. That's a common knowledge now. And in books, you can read many books about this. You can read science emerging in this field, which is very convincing. People have done it in mice and rats, but now in humans, we have to prove that simple exercise and a great diet is very good for your blood vessels. And then what are the things to be worried about, like in specific, maybe, periods of time? So, for example, something happens like prenatal hypoxia now, and other things. So, what are the dangers that those bacterial cells and, in general, neurovascular system is prone to? Yeah, absolutely. I mean, that's something we work with Dr. Tebow, who's at our hospital, on this team. Perinatal injury. So, you have to understand one thing. So, the brain vasculature is very sensitive to injury, and the consequences are long-lasting. So, if you have, during these critical plasticity windows, which is the word we use, an impact on the brain vasculature is going to give long-lasting neuronal consequences and behavior than autism, for instance. Hyperoxia, so too much oxygen at birth, has been shown by Dr. Tebow recently, in collaboration with us, to drive cerebrovascular changes, reduce blood flow, and then long-term neuronal deficits. And in mice, it actually triggers behavior that are reminiscent of autism. Hypoxia, you know, hypoxia is a classic injury around birth. You might have heard about cerebral palsy. If you have a perinatal injury, such as a perinatal ischemic event, it leads to death of neurons and other regions of the brain, and cerebral palsy. And people have recently linked perinatal hypoxia to autism. So, you see the long-term consequences when you hit that critical window of plasticity, perinatally. So, that's exactly what we should think of if you know a target in the vascular system. Well, treat early to help or to prevent a course of things that could happen during life. Now, we can talk about the interactions between neurovascular system and neurotransmitters, like serotonin, dopamine. What is the interaction here, and how does it affect depression or other brain disorders? Yeah, that's an excellent question. So, it's, again, a big field of research. And I can start by telling you, for instance, that those neurotransmitters you might know, which are very classic, if you see serotonin, it reminds you of different brain functions, but also depression, because we know that serotonin levels are low in depression. Dopamine, you might relate to the effect of, let's say, some psychostimulants, such as cocaine, which is a blocker of the dopamine reuptake to enhance the effect of dopamine. Adrenaline or norepinephrine, which is the same thing, is a drug released for an action of defense, and this is affecting the neuronal system, but also vascular. So, serotonin is a potent vasoconstrictor. Serotonin is going to close your blood vessels. Noradrenaline is going to also close the blood vessels. Dopamine is actually less studied, but these are responses which are adaptive responses. And then, these are not just neurotransmitters. They actually act on different pathways, including directly on the endothelial sense. Acetylcholine, you might have learned in your course a long time ago that acetylcholine drives muscle contraction through the neuromuscular junction. Well, acetylcholine does the opposite effect on the vasculature of the brain. It's a vasodilator, so it's going to open up the blood vessels. And you know that acetylcholine is usually secreted when you need arousal. It comes from a deep region of the brain, the basal forebrain nuclei, and it projects onto the cortex here for dilating blood vessels. In the same time, it regulates neuronal activity. So, yes, neurotransmitters have a direct effect on vascular function in the brain. And just to finish, serotonin is low. You can imagine in depression that it will affect the blood flow in the brain. In Alzheimer's disease, one of the first systems that is disappearing is the acetylcholinergic system. So, you can imagine that it has an effect on blood flow as well. And it is known that all those diseases have a vascular component. So, that's a huge field of research. Now, just to have a general question about how big is the research community just talking or investigating about neurovascular systems? Because, well, thinking about autism or depression, we usually just think about neurons and neurotransmitters. But this other component of it, which makes, well, incredible sense, because, you know, you want the neurons to have oxygen, to have glucose, and it's by the blood flow. So, how big is this area of research? Yeah. So, if you would just keep the area of neurovascular interaction field, it's big. You have lots of people working on neurodegenerative diseases. So, lots of people working on Alzheimer's disease, for instance, in human and animals and laboratory models. You have lots of people working on Parkinson's. Recently, the field of depression and its relation to the vascular should develop. And we actually have one famous scientist in Canada, Caroline Menard, in Quebec City, who has developed her lab around BBB regulation in depression, and she finds very interesting targets. Concerning autism and vascular, well, we are the only lab. So, it's a small field, and I'm very happy to be developing this niche. But otherwise, the field of cerebrovascular biology is pretty big. Awesome. So, let's switch the gears a little bit and ask Dr. Lacoste, what do you do outside of the lab? Is there any hobbies that you're trying to unwind from all this complexity of neurons and neurovascularism? I do a lot of things. So, first and foremost, I am a husband and I'm a father, so I have a cute little family, which I'm very happy to get back to every night. But that's not a hobby. In terms of side hobbies, so I do a lot of photography. So, I love art, and I actually think it helps me in my science, because illustration and demonstration have to be so thorough and convincing to an audience, that if you have an artistic twist to it, it's going to be healthy. So, I love photography, and that helps me in imaging within the lab. And I also do a lot of astrophotography, which is the complete opposite of what I do with a microscope. So, I love extremes. I look at molecules, but I also look at nebula, which is something I do in my background. And I play piano, and I play the guitar, and I read a lot of books. So, yes, I have a life outside the lab. So, it's a big issue of hobbies. And I was wondering if you could talk to us about a time that you have faced failure, maybe in your career or just in academia in general. How did you cope with it, and how did you step up again, and what did you learn from it? Okay, I could spend hours on this. So, I kept on facing failures. So, I come from being a, first of all, I have a pronounced attention deficit. I have been diagnosed with dyslexia. I am dysorthographic. I have a lot of issues, and I'm French. It's a huge phenotype. But more seriously, I was a very, very average student. I had difficulty concentrating. I had to redo one of my secondary classes to actually retake off. So, that was a big failure, but that helped me a lot because I could reset the clock, and it actually helped me a lot. I had specialists who helped with my dyslexia, and I could have been treated for attention deficits, but I did not at the time. But it was a long battle against myself. And when I discovered my passion for neuroscience, it was an awakening that something that people should know is the field of neuroscience and research in neurobiology, and probably other fields as well, maybe less astrophysics. You don't need much math. You don't need much chemistry. You don't need much expertise when you start because you learn everything on site, on the go, at the bench with your mentor. So, all the things I know today, I've learned them after graduating school and after all these diplomas that you should have. So, failure is my history. And then nowadays, well, as you might know, to keep a lab working and alive, you need to find funds, and we keep on writing grant applications, and we keep on failing because it's very competitive. And to find one, let's say, CHR grant to fund your lab for five years, you have to fail maybe three to four times before getting one of those big grants. So, failure is part of the game. Failure is part of science. And you can only learn from failure. So, successes are good, delightful, you celebrate, and you know, the top of the wave is very agreeable. But when you're at top of the wave, if you surf, you know that you go down very fast. So, it's a roller coaster, and then people should know that science is up and downs. But the downs are also the way you take off. And the taking off to me is the best one. The top of the waves is I know something else is coming. But the climbing phase is amazing. But you have to start from low, right? So, please, continue to fail. This is my message. And can I ask you, if you were not a neuroscientist, what career would you choose? Ah, that's a good question. People like me with an attention deficit and hyperactivity, they think they could be so many things at once, and it's hard to choose. When I was young, when I was 18, I wanted to be a rock star, I wanted to play the guitar in front of a big stadium. When I was younger, I wanted to be a fireman. But more seriously, I wanted to write books. So, I could have been a writer, and I think I could have been a musician. And you have followed on those interests? I didn't give up, but I kept them as hobbies. And I must say, I had a very good advice from my parents. They said, you know, don't make your hobby your job, because once it becomes your job, you lose it as a hobby. And that's very sad. You have to keep your hobbies as hobbies. And then, you know, that was a wise choice. Well, that's great. And another advice from my parents is always try to keep the balance between your hobbies and your career. And if you want to like make connections, I guess you could say the security system of our brain, blood-brain barriers, we're always trying to keep that balance. So, we could definitely consider that. So, now we can maybe talk about teaching as well. Last year, you won the Excellence in Teaching Award in Faculty of Medicine. How do you approach teaching in general? What is your relationship with the students? Yeah. So, fortunately to me, this is something I think I have in the blood. So, what I mean by this is I don't really force myself to be approachable. So, the first thing I do is telling the students I don't care about the details. And I always say when I teach, on each slide I present, we don't really pay attention to the names of the molecules, to the structures of the molecules, but what I want you to learn are the concepts. Because if you learn and understand the concept, this is what you will remember, even a glimpse of it 10 years later. But I wish I had teachers that would say, don't learn all this by heart. Don't speak all on the final exam and then forget the next week. Teachers like yourself. So, I basically teach the way I would have loved to be taught. So, then what advice would you have for the students who are trying to just understand what is research or trying to approach this scientific mindset? Yeah, because as an undergrad, we always struggle to find the right prof. And as you already know, and our audience knows for sure, that we have to send 50 emails, 100 emails, and then maybe two or three profs get back to us. So, I'm just wondering if undergrad students specifically want to be involved in your research, what skills or knowledge they have to work on, and how should they approach you in case they want to be involved in your research? Okay, well, so the answer is quite simple, but at the same time, it might be complex for some people. I don't look for any skills apart from the people skills. So, and I mean, fortunately, it's a good point to have. Unfortunately for students, my lab is rapidly at high capacity, and usually when I answer, so I will always answer a request. These days, I answer no very often because we're full. So, that's the only problem we have. And I thought it was a good point to have. But the only thing I'm looking at is the inner drive. When I meet a person in my office for, like, I'm not evaluating anything I've done. Is this person genuinely interested in what we do? That's a bonus, I would say, if you come for a good reason. It's normal. It's the game. Everybody applies to 15 labs, 20, 30 labs. You are going to craft your letter to the lab you're applying to. That's the game. That's normal. You would do it for any job. But the day we meet, if I feel you actually have a genuine interest in neurobiology, in neurobiology of disease, you don't have to have an interest in vasculature. We will drive this interest in you. It has to come from the inside. I cannot implement in someone the flame of neuroscience. I can help someone stay on track. The way I mentor even my lab members is I guide people to stay on track to avoid hitting too many walls. Yes, I think it's good to hit a wall from time to time, but I want it to be not too much of a huge crash. So I put an airbag in between. That's my job. But the only advice I have to people is be yourself. Don't use chat GPT to write your letters of motivation. Because I'm going to even tell you, sometimes I take a letter which is so well perfectly written, and I go to chat GPT and say, what are the chances you wrote that letter? And chat GPT says, there is 95% chances that I wrote that letter. So you won't fool me. A letter which is very personal, which has typos, which has mistakes, but is conveying that passion or that will to discover. That's going to be the letter I'm going to be interested in and following up with the student. Okay, so be yourself. And don't go meet with someone that you are not 100% sure you're interested in. As a student, don't reach out to people, you say, I need to find a position, you know, I have no choice. I go to this person, but it's not really my passion or interest. Don't even bother replying, because we will feel that lack of connection. Well, I'm sure the folks really enjoyed the last part of trying to be yourself and know yourself. I just want to maybe it's going to be a little bit philosophical, but just wondering, what is the purpose of your life? You say you're passionate about neuroscience, and basically creating a great life for your kids and all, but what is it that you as a person personally looking forward to achieve in your own life? Not to get the Nobel Prize, that's for sure. No, provide a meaningful contribution to the society. I mean, we are here for, okay, let's be lucky, 80 or 90, if you do exercise. To leave a choice, but more than this, to have a meaningful contribution to our society, while not impacting our planet, you know, too badly, because, you know, planet doesn't care about us. She doesn't want us. So let's have a symbiotic relationship with the earth, and while contributing to the society in a meaningful way. That's the main goal of my life. Perfect. That's awesome. Dr. Lacoste, it was a fascinating conversation. Thank you for being a guest in our podcast. Thank you for the invite and fascinating discussion. Thank you very much. Have a good day.