 We mutate it and we'll try to screen it and see if any of the mutants from this molecule can sense voltage inside themselves Library was up to 10 millions up 10 millions individual clones Screening of each cell Manually take several so minutes So it means I wouldn't be able to finish probably this screening of this library till nowadays if I start doing it manually And Ed was saying oh, how about we just make robot to do it for us? and This is how we end up with designing a special robot that can Image very large population of the cells Automatically pick the best cells expressing the voltage sensing molecule And select using a micropiped and everything in a in automated mode in fully automated mode I remember with this day when I click start it took me about two years to make it to happen But once it's everything was set we click start button Robot did it for us for two hours while I was drinking coffee at Vendor this process. I take the tube With a few cells selected from the plate I clone the genes and one of them was the Archon voltage sensor that we currently using for voltage imaging in vivo Boom, what's up everyone? Welcome to simulation. I'm your host on sake and we are on site at MIT Massachusetts Institute of Technology in beautiful Cambridge, Massachusetts We are now going to be talking about neural imaging and interfacing. We have Dr. Kirill Piatkiewicz joining us on the show. Hello Good afternoon. Thank you so much for coming on really appreciate it. I'm very excited Also, very grateful to Sierra Nush for introducing us Bob Knova. Thank you. Huge shout out for those who don't know Kirill's background He's a research scientist at MIT Media Lab in the synthetic neurobiology group focused on advanced neural imaging and interfacing Techniques and you can check out Kirill's links below as well. So check out the work We're gonna be unpacking a lot of really cool cutting-edge stuff So let's jump into this with one of our favorite questions. We like asking we find ourselves as stewards of earth What is your current take on the state of our world? state of our world I In everyday life the most thing I enjoy is our creativity and I think everybody Would enjoy Himself a lot more if we can be creative and uncover our potentials and creativity So if I imagine our world if ideal world like ancient Greeks when we were doing some of Like earliest have and we were thinking about world without doing much of a hard work and let's imagine other robots Doing it for us and this is what I would like to achieve So everybody can do whatever we want and be happy and I think this is the most powerful thing we can do in our life be happy be creative and Get this kind of Yeah, like to reveal our potential and at same time I would like to be creative and revealing potential in the full harmony with nature. Yes, this is what I imagine This is my perspective. This is what I would like to achieve And this is why I also study science and study and I tried to do research because I want to understand the nature better Understanding nature better. I would believe that it will allow us to live in better harmony with it Because I'm very concerned. You know, there are lots of stuff going on a climate change Some and this is think we still don't understand very well And I think everything in the world is connected and we understand the world starting from very small atoms Up to entire Universe with now people putting this images of entire like not entire but as much as the Hubble could image And if we can scale it up and see, okay, this is a harmony We can understand everything this would be super cool and and in and why I say again creativity because in science when we do research Creativity is I think is a driving force creativity and curiosity is a driving force of our our Like when we're trying to understand the world this is and do research. This is what we We need first of all these two things. Yeah, yeah in I love that so much that the Full potential of every single one of these human animals to be able to be as fully actualized into the world and To be able to actually have this this tree that every single person is a seed to have that have the roots Have the right nutrients so that they can have the best possible fruits and flowers for the civilization is so Important and I love that one and and to be able to update the code of our world to make that easier More effective to deploy the next advancements and code for that is so critical and like you said with nature in harmony With nature so critical. All right. Let's go into the journey. So Your kid and you're growing up in Belarus. Yeah in a small town about 10,000 people Population 10,000 people population. Yeah, see this is some small town and then I want to know how you got Interested in science. You talk about science is such an important part of Your life and of pushing the edge for our world So how did it you get hooked into science at the young age? So the earliest memory of me doing experiments what I have right now It was probably first grade of elementary school when we found the pieces of calcium carbide and when you put it in the water is how to release a citulin the gas that back when we're used to Solder the pipes and we were putting it on fire. I really enjoyed and When I get back home My brother was seven years older than me and he was already studying chemistry by that time when I was in elementary school I found his books on chemistry and physics and I was I start reading Didn't understand much. I was Very fascinating looking on the pictures in the in the books without understanding much of a text But I peeps great. I really got into it and this is when I first time participated in Chemistry Olympiad Started from a chemistry. Oh, yeah ice and What is your project in the chemistry Olympiad? Oh in the back when is In the Soviet Union system back when it was still a kind of Soviet Union system It was a mostly solving the problems and you compete with other with other pupils or school students To get the highest score to go to the next level go to the next level Yeah, and I also was very lucky because my parents were working at in industry at My mom was a dairy factory. My dad was at mechanical factory. We had an access to the lab Ah, and I was always all can you take me through your work? I want to check out your labs Yes, and I was asking people from the lab Can I take a little bit of chemical and I can do experiments on so I had a small home lab For all my middle school and this is how it got involved and it was getting more and more and more every year Yes, so Next time what I said, okay, I don't want to go play To a backyard with my friends. I want to I want to mix some chemicals and see what happens. Yeah. Yeah Interesting, so that's in that's such a critical part of being young is that when you get The tools and resources that you need to be able to explore what interests you like being able to have Your lab at home and be able to play with it almost everything Although my parents didn't like it too much because it not not always created a good smell But I tried to sneak in and do some experiments Yeah And then did that's interest in chemistry then continue to when you went to Moscow? Is that how? Yeah, so I was a winner of international chemistry olympiad and I was a winner Uh, okay, silver medal the silver medal that's still wow And how old were you then? It was 15. Wow. Good job. Yeah, and I was During the training at Moscow State University before olympiad. I talked to a Faculty where and they say oh if you if you're a winner, you will invite you without any Exams to enroll the Moscow State University chemistry department and back when it was my my dream to enroll School of chemistry at Moscow State University because it was the best school of chemistry back when in entire post-soviet space, yes Okay, and so I didn't think about just like that. You get silver medal They accept you in for uh for for the chemistry program. Correct. Oh sweet. Okay So you make the move to Moscow And you start studying chemistry and you continue this process of pushing the edge of science playing with chemistry Yeah, I was happy. I got an access to a bigger lab Yes, there's more chemical with more flask and I started doing experiments. Yeah, I was doing organic chemistry What's the for uh, metal organic chemistry actually first and second Year at college But uh, I also very quickly realized, okay, this is not very healthy unfortunately, we didn't often follow all the safety rules And I could tell yeah, I I feel like okay. I I smell bad after the lab Because we didn't have a proper ventilation and I decided oh, maybe I should Work a little bit with the safer chemicals and I this is how I got a transition into a uh department of uh Natural compounds chemistry of natural compounds. Okay, I decided to work with DNA RNA and uh Polysaccharide something that we consist of yes, and I said, okay This is going to be a little bit safer. Yeah for my health. Yeah, interesting. So some of the initial chemicals If you're playing in labs that don't have good ventilation systems We can end up inhaling those and that cannot be healthy So that's very important to have a really strong lab safety But then that got you interested in the life sciences with DNA RNA Yeah, I could do still chemistry very advanced chemistry But with the materials that I could not eat but we definitely require much less safety rules Yeah, and then what were you doing with DNA RNA polysaccharides? What were you doing? Oh, so back when uh In uh In the department. I start working on my uh diploma work So my my interest was in Regulation of expression of genes in bacteria. Mm-hmm We were trying to understand the mechanisms of how bacteria switch over gene expression During different Conditions during transition into different conditions some heat shock or some other negative environmental influence How it does how fast and What we can learn about it. So it was pretty fundamental work on Gene regulation Interesting. So the environment of a bacteria can cause the gene regulation to change quite sometimes quickly differently from normal and you would measure that out and log it and then teach it to people. Yes Interesting and then that can potentially be used for a lot of our life sciences today in different ways we can use the Gene regulation and expression in tons of different ways potentially for humans and for our world. Yeah, yeah Yeah, and it's it's like a big catalog that's unexplored right now and we have to figure out. Yeah Yeah Okay, and then how did from Moscow you go to bronx in new york city because that's this is a big move Yeah transatlantic transatlantic move. Yeah, how did that happen? So during uh, how we started gene expression We use fluorescent proteins because it's very easy This fluorescent protein once you get expressed in bacteria. You can easily visualize bacteria under the microscope and uh We had my department had a connection to the lab at Albert Einstein College of medicine But we're looking for a graduate student to work on the fluorescent proteins. Cool. So I got an invitation for the grad school and I didn't think much and say yeah, of course I would like to continue my work in new york. I got invited to apply for visa But I I remember I had like last 600 dollars in my pocket. I bought my ticket I have very small luggage and I flew to new york. I love it huge risk. I love it. Yeah, I I was I decided to risk it. Yeah, and it also was my dream because back when during my Uh, undergrad I was reading lots of papers. Yeah, my favorite papers and I saw that all this work is done in the united states And I wanted to see oh, is it really so cool? I want to go and see myself by myself Is it really so cool? Yeah 90 percent of work was done in the united states. So I wanted to to get this experience. So I didn't think much to get tickets and Fluid in three days. I think it was yeah pretty quick Okay, and then when you get to bronx Then you're doing cool things at the albert-einstein college of medicine working on the development of novel fluorescent proteins For imaging for in vivo imaging. Yes. Yeah, so teach us about what this is like uh so very often In biology what biologists want uh, uh, very often they say Seeing is believing if I see I believe yes, and uh, in order to see things inside of the cells We need to light them up and uh in 1978 osama shimamura Uh in the bay on a west coast hired bunch of Middle school kids to catch aquaria victoria for him in the bay So and and bring them to his Small laboratory. It was summer laboratory for the section an extraction of a special pigment That later on was used to identify the gfp green fluorescent protein. Wow That later on martin chalfie clone the cdna and express it in Celigans, so first application for gfp was in celigans It was on the cover of science journal in 1994 and later on roger tian used this cdna to Evolve artificially In a tube in a pcr tube evolve all the aspect of diversity from blue to yellow. Whoa 2008 it resulted in a noble prize to three scientists asama asama shimamura roger tian and martin chalfie and Back when when I joined the grad school 2007 it was Way for this development of the new colors new proteins with the new properties Uh, it was extremely popular and extremely useful for biologists to put the different to highlight different structures different molecules inside of our cells So we can observe it in real time under microscope. So when now we can see the things and now we can believe it. Yeah But we decided to scale it up and we decided okay We don't want to do it in a cell in a petri dish We want to do it in a cell in a whole body in a in a living organism. Okay quick. So We are taking fluorescent proteins from fish It's jellyfish and corals. Mostly. It's jellyfish and corals. Okay 90 percent of them coming from this too Okay hydrazoa and the antazoa hydrazoa jellyfish is going to hydrazoa class corals from antazoa and so They can express fluorescence Fluorescent protein so they can express fluorescence for fluorescent protein expression. Okay, so We took that fluorescent protein expression and we were able to figure out how to express from blue to yellow colors, yeah, so we were able to fine-tune these proteins to Emit the light In this range emit the light in this range and then Then you took that ability and took it in vivo into the cell And we're able to say I want to tag the mitochondria for example Anything we could do anything and then you could look under the microscope and see the fluorescent the mitochondrial Lit under the cell Absolutely. Yes. That's beautiful. Yes. Yes, and we could do it in many different colors We can resolve many different colors and we can do multiplexing Do multiple Things simultaneously. Okay, because you could do blue for specific ribosome and yellow for the mitochondria And then oh, wow. Yeah, that's so cool And uh, but when we decided to do it in vivo How does it know wait? How does how do you how does it know to go to the ribosome or the mitochondria? How do you right? So Nature is very smart Everything is very very regulated nature falls very well Falls the rules and we can understand these rules and use them For our purposes to study and in order to send the protein to mitochondria. We Append it with a small sequence Once the sequences in the cell floating in cytoplasm is get recognized by cell or machinery And get exported to mitochondria. It's like Signaling sequences. Okay. So you add a signaling sequence to the protein and then and then the cell will say, okay It's go to this area And depending on the signal that you add to the protein it will tell it to go to a different part of the cell So people figure out many different ways to highlight different different structures Single molecules or some other subcellar structures. Okay. Okay. Cool. Cool all right, so then That going to from in vivo you started saying that you wanted to take that into human Or at least animal Yes to to Whole organisms. Yes. And what's happening with the whole organisms that the shorter wavelengths of the light The harder is to catch its emission. So if you ever put your hand on a on a lamp You see you saw red. Yes. Did you yes? Yes. Yes. It's not because of blood you have in your hand Yes, yes, but because the hand is like a filter It's filtered all the wavelengths except the red one So red gets through and you see interesting you see your red So and what does it mean? It means that the red color or red light Is the light with the biggest penetration long enough wavelength to be able to get through our cells Yes Our tissue our tissue. Yes. Interesting. But blue and purple cannot No, yellow green. No blue. No So we have much shorter Distance so they absorb more and we scatter more It's a it's a factor of two. It's scattering and absorption Interesting. Okay. Okay. And as a result the my major goal was to Make fluorescent proteins with a long enough emission spectrum So we can do a whole body imaging in of small animals like back when I was working with mouse mostly And how did that go? It wasn't very it didn't work very well in the beginning So we were trying to push GFP and other proteins that we found in corals To the spectrum up to 700 nanometers. So this is an edge of what our eye can see. Yes Beyond 700 is getting the spectrum for eye getting very difficult to recognize and Again, we got a hint from Roger Tien in 2009 he publishes He published paper in science on using bacterial phytochromes. This time we found different type of organism in a soil Bacteria We use red light to regulate Their cycle and why I was surprised why red light in the soil bacteria because this is the only light That can get through the door with bacteria living in to get them activated and this protein is called bacterial phytochromes And I was surprised. We're pretty abandoned and this protein had a completely different chromophore That could bring us beyond 700 nanometers. I think the most redshifted fluorescent protein right now from bacterial phytochromes is 720 nanometers So you need night vision goggles if you want to sit with your eyes So this is this is my this is how I The goal was can we push it to in vivo? We tried and failed with a fluorescent protein from jellyfish and corals and we were able to make it to work in corals Or in from bacterial phytochromes from bacteria. Yeah Okay, and then how did you then go from the alborinac scancology of medicine to Cambridge? The major Application that I was working for this fluorescent proteins when we were imaging was cancer research And I think it's very important research and can be very very impactful Potentially lighting up the cancer cells to see how we get through the tumor To the bloodstream and from bloodstream to the lungs So we our goal was to trace metastasis of the cells because why people dying from Cancer it's most often because of our lung like lungs getting clumped with lots of cells from a tumor from Metastasis where we're getting into lungs start propagating and people suffocating. So this is was the major Thing if we could stop metastasis it means we can at least slow down the Cancer in the people and our goal was to develop the methods That could allow us to visualize how the single cells from a tumor site go into the lungs in the whole body In this case using this kind of model organism, we will be able to treat we will be able to find Treatment as fast as possible We for example given Some drugs to a mouse and see if we can stop or reduce the speed of this metastasis And during my Uh phd work I was reading a lot about other types of light sensitive molecules And one molecule that fascinated me a lot was chenorhodopsin 2 was published in 2005 in in journal neuroscience and It was shown that expression of chenorhodopsin 2 molecules a wild type molecule from another algae. It's unicellar algae Can allow us to Activate neuronal activity with a single spike precision Wow And this give us enormous enormous application for neuroscience in order To for example to crack the neuronal code. It will be very very useful Using light to either activate or silence neuronal activity. This is something that Was predicted or not predicted but something that was anticipated in 1978 when I think kreek said One of the people who got noble prize for dna structure He said it would be very very useful to have a tool That would allow us Optical control neuronal activity in vivo and this is happened in 2005. I was extremely fascinated by chenorhodopsin and the first Author on this paper at the same day when I was reading about chenorhodopsin was in our At albert nashan college of medicine giving a lecture. It was at boyden And I Attended his lecture and I decided okay. This is He's doing great research. I want to be part of his team advancing new optogenetic tools for neuroscience I mailed him right away. I I even remember this first time less than five minutes He shoot me back. Oh, do you want to stop by my lab and we can chat about it more? And I said of course We we take in the car. I'm I'm driving up to cambridge When I met him I proposed him some research and he told me Why don't you come over and work for me? I said no problem And uh, yeah, and and gave me a postdoc position right away. I was very very happy I joined it in 2013 Wow, wow, okay, but then from that was 2006 was the paper and 2013 is when you joined the team. Yeah, so uh, it was Several years not so many people believed in interesting and It was in 2015. It was 10 years of optogenetics and I think nature neuroscience published a small article about Quotes of different people and you can see that 50 percent of the people think oh, it's cool, but it's not gonna go anywhere you know and But 2010 it was methods over a year. I think 2010 so it was very very very rapid And I was already on the wave and people realized. Okay. This is this is gonna be very huge by that time It was very very huge. Yes. Okay, and I wanted to be part of it. I wanted to make it even bigger Interesting. So yeah optogenetics for neuromodulation For either exciting or inhibiting neuronal correct cells All right now I'm interested to know what you came in with the proposals you said that yeah And it was like yes come on and join the synthetic neurobiology group as a postdoc Yeah, what were the proposals very when I talked to it for the first time I very quickly understood He's a very big thinker. He thinks very very big and I decided in order to impress him. I also got a think big uh, I was very interesting in a It was also a time of a singularity talks people were talking about singularity And I was thinking about cyborgs that would combine artificial some part of Probably silicon hardware and carbon hardware our our brains and We knew that it's very difficult to combine these two together materials Especially if we insert the electrodes into the brain we get immune response It sells dice around the electrode. It doesn't save for too long But if we interact with silicon life and carbon life interact through the light it's much safer And what can give us the ability to interact with the light is Optogenetic tools. Yeah, we can both Transmit information to the neurons excite them or inhibit them at same time we can read out this information by light Okay, let me give a quick example for or maybe something that's very relatable So something that we can consider even optogenetic is how we take in visual Information all the time. Absolutely. So we're so as we take in stimuli of light reflecting off of chairs and tables and all that stuff We are modulating neurons. And so that is optogenetic in that sense And molecules in our retina rhodopsins responsible for interacting with the light very very similar To optogenetic tools that we currently using. Yes, it's a type one rhodopsins from algae they call so microbial options for algae and bacteria and fungi And we have type two rhodopsins is one of the example in our Eyes, yes rhodopsins rhodopsin interesting So it's very similar mechanism. We get excited in our eye and we Generating certain signals and you wanted to make it easier for silicon to interface with the carbon in us through optogenetic So would this be somehow? through the optical Modulating light and then that modulating neurons No, but when I was thinking that we will have to deliver options into our neurons and get some optical some kind of Illumination devices and camera around our skull For humans, this is how I imagine so we we can talk through the through a skull using light We excite and we collect the light through a skull although, but we will have to genetically modify our neurons Go and express something. So this is something FDA still doesn't approve Can you go? From outside the cranium can with light So red light can go through Interesting not far, but it's for mouse. We were able to do it with red light red light. So wow Uh, we now can do non-invasive for example calcium imaging using mean for red Sensors, yeah through the skin and through the skull interesting although resolution is dropping It's not a single cell resolution, but we can do non-invasive. Yeah, yeah, not single cell Although not due to the too much scattering, but yeah Interesting. Wow. So this is my idea and then said this is a great idea It's not gonna work right now. This is not the right time for this idea, but uh come and come work with us Okay, so then that was kind of your uh, 2013 Getting into optogenetics studying that also studying expansion microscopy being able to expand the tissue Actually back when I just joined the group expansion microscopy didn't exist, but what was that? 2015 so It was published in end of 2014 when I joined the lab Paul and Fay and I think Ishan they already had an idea Or we want to make things bigger in order to Get a better resolution of small features inside But uh, but when it I think even the term expansion microscopy wasn't yet invented. Yeah Uh, but yeah, it was very very rapid development because Uh, we very quickly figure out how to expand the biological samples Isotropically preserving Some labels that we could uh see under microscope You preserve the shape of the tissue as it is yes That's so critical and then be able to do things like have the fluorescent proteins as well Yes, yeah, so and uh This is where My expertise helped a little bit when we brainstormed with Fay. He told me oh, I can anchor Proteins right now into the gel And I thought can we need to do it with the gfp because gfp is robust enough to survive expansion Digestion expansion and I remember I gave him samples with the fluorescent proteins in cells He expanded and his workouts beautifully from a first attempt. We never repeat this Experimented to work out and we say okay. We gotta we gotta hurry up and publish it. Yeah So cool So that that is actually a big testament to when you put together the Multidisciplinary thinking Where you come with the expertise of fluorescent proteins With the expertise of pushing expansion microscopy and you're like hey add this Yeah, that's so cool. It was a unique environment It's still a very unique environment when so many different people was very different Background and expertise working together and talking on a daily basis. This is where brainstorming happening on Yeah, all the time and this is when We're getting new ideas new crazy ideas to try out People I enjoy I'm enjoying it a lot. I think this is very unique. This is very unique It's super unique the two words that I think have been A major part of my understanding of of synthetic neurobiology Most recently has been optogenetics and expansion microscopy. Yeah, and I think even expansion microscopy recently started to take over even more Yeah, I know I I've been participating in several conferences and people When we talk to me, I am saying, oh, I'm in that boy in the lab and he's oh expansion microscopy lab Not so many people That's so great and all right and now I want you to take us into these novel tools and methods for neural imaging and interfacing the ones that especially like You know the ones that you worked on you said about Four years of the time from 2013 2019 and six years But you work four years specifically on optical voltage sensors. Correct. Yeah, so yeah So teach us about what that that is is a robotic multi-dimensional directed evolution approach applied to fluorescent voltage Reporters. So when I proposed this idea of interfacing brain with the machine using light We had perfect epigenetic tools so we can communicate information to the neurons But back then we didn't have any tools that can communicate information from the neurons back to the machine This is one of the reasons why I said, okay, this is not the right time We don't still have all the tools set for for this kind of approach And we were missing the molecule that would convert the light That would convert voltage of the neurons back to the light So now optogenetic convert the light into a voltage. We need something voltage back into the light. Yes, and that proposed Oh, how how about you? you develop a voltage sensor that Can be compatible with optogenetic control and can report Uh, voltage with a sub threshold Precision at a biologically relevant time scale because neurons are the fastest Cells in terms of changing for membrane potential. This is how we communicate like millisecond Even microseconds. Yeah, we're sending very short electrical pulses along with neurons Along with axons and this is how we communicate. So if we want to understand The neurons we need to Record the action potentials. We need to record the voltage across the plasma membrane So we're talking right now while you and I are talking we have billions of neurons That are firing and talking to each other and talking to each other Although we don't see it. We don't see it. Yeah, and we barely feel it even you have to really You have to really try and tap into same as we see we look at this wires We know there is electricity going on there, but we don't see it So we need some sort of a molecule that would sense a voltage and convert it into the light a molecule It's a molecule. Yes. It's a protein. It's a protein nature. It's a protein That can sense voltage across the plasma membrane Convert the chromophore in a way that it's going to be fluorescent. So every time neuron spikes we see the increase of The light flash in on Cheap of our camera and then Did you do that in vivo first? So We didn't have this molecule. It was just imagination imagination at first. Yeah. Yeah, although we knew some of Possible molecular mechanisms how to convert voltage into the light We didn't have a molecule that would work very well in the neurons and And we didn't know how to make it And what we decided to to do we decided how about we just create very very large library Very diverse library of different different genes using a special One special unique molecule archaeodepsin archaeodepsin 3 it's also was this molecule was discovered by it first time We mutated and we'll try to screen it and see if any of the mutants from this molecule can sense voltage inside themselves Library was up to 10 millions Up 10 millions individual clones Screening of each cell manually takes several minutes So it means I wouldn't be able to finish probably the screening of this library till nowadays if I start doing it manually And Ed was saying oh, how about we just make robot to do it for us And This is how we end up designing a special robot that can Image very large population of the cells Automatically pick the best cells expressing the voltage sensing molecule And selected using a micropiped and everything in in automated mode in fully automated mode I remember this this day when I click start it took me About two years to make it to happen. But once it's everything was set. We click start button Robot did it for us for two hours while I was drinking coffee at Vendovis process. I take the tube With a few cells selected from the plate I clone the genes and one of them was the Archon voltage sensor that we currently using for voltage imaging in vivo Whoa two years to set it up and then two hours to find it with the robot But okay two and plus two hours to quality. Whoa okay, so I'm as a as a you know an advanced monkey. I'm trying to understand this and Okay, so there's You really you want to be able to have a way to sense the voltage Yeah, okay And the the the modulation you want to be able to sense the modulation with these voltage sensors that can sense um Very very small amounts of voltage Correct, okay, and then you also need the robotic assistance to be able to see that that action So robotic assistance we need to develop this molecule to develop so We back when we knew that archer adeptsine was Dimly fluorescence and its fluorescence Was modulated by voltage It was done by adam coin and I think we published this work in 2011 However, this molecule had many disadvantages and didn't work in neurons We wanted to make it in to work in neurons and uh, we use this evolution It's same method with nature using what nature does it's creating genetic diversity When applying selective pressure see who survived parents survived we give the next Breed and the process repeats again multiple iteration. So we do something similar in in the tube and much much faster We took the molecule with archer adeptsine molecule That didn't work in neurons It wasn't very bright didn't localized to the membrane, but it was voltage sensitive and it was fluorescent And what we were able to do we were able to enhance all these properties By mutating randomly mutating some positions And but in order to after we mutate in order to understand what mutant out of his 10 millions Yes Unique mutants are the right one. We need a robot. Yes, we do it for us Automatically and the mutants did what? So mutants were expressed in mammalian cells And we were able to assess the localization. So we so first property that we assessed it to make sure that Protein is localized to the membrane because the electric field in a cell only exists across the membrane Once you want more than one nanometer away from the membrane. There is no more electric field. It's a debi Radius it's it's decaying very very quick. So first we need to make sure the Molecules are not on the membrane expressed well Second we want to make sure that molecule Shows sufficient level fluorescence in order for us to image And third we need to confirm that during the changes during the modulation of voltage Across the plasma membrane it changed the fluorescence So we had to optimize three properties in for 10,000 or 10 million of Independent independent clones and the ones that were the successful mutants were the ones again that did Yes, we can repeat it several times and actually we did it twice. Yes Okay, and that those those successful mutants that you took and that could repeat They did what again they were able to Sense the world we were localizing to the membrane Sense the voltage and were bright enough for us to image it using optical using Fluorescent microscope Okay, so we're just making it better and better and better. Yeah, so break it down one more time We could go past the membrane the the Yes, so it can get Incorporated into the membrane Okay Because only voltage exists across the membrane. Yes. Okay. Second it possessed some fluorescence Yes, so we can image and third the fluorescence depends on a voltage across the plasma membrane the higher the voltage the higher fluorescence Okay, okay. Okay. Just barely understanding. It's just barely tiny I can tell you What How it looks like under microscope you see the neuron with blinking. Yeah You shine the certain light and you image where fluorescence and it's blinking And we know that each blink corresponds to action potential. Yes. This is the main idea. Yeah But to make this molecule we need to do the 10 million Mutations and try and find the neurons that could Through when you do optogenetics it will show its action potential. Yes. Okay Still child Understanding. I love it. I love it. It's because it takes Years of really diving into to be able to to to get it but Okay, so then the Now teach us about what with that technology, what can you do with that? In We can Read minds How yes, this is a big old very very far. This is the big old. This is very very far. So with this technology We were able to image Activity of the neurons in behaving animals with a single cell single spike precision so In We believe that every neuron is important. So there are several classical papers showing that Even driving of one neuron in the brain Can change the status of Anymore it can go from aggression to fear the butterfly effect By by changing just activity of wine. I think it was yeah classical paper in published in nature Yes, so it means every neuron in our brain Can be very very important in order to understand the brain It means that in order to understand the brain we need to image We need to understand how every cell Spikes and how they connected to each other So you can take the mutated neuron that can be that can be stimulated and read Upto genetically that you can then take that and potentially Implant that neuron what we do we We inject viruses Into a mouse brain you inject a virus Adenos recombinant adenositiated viruses. Yes with viruses gets inside of the neurons and make this neurons express our molecules chenorhodopsin and voltage sensor and now Oh my gosh labels because drive and see these neurons. So we were able boss Activate the neuron activity and see could you did both so then you read what the mouse What the neural activity so what we did next we put animal on a ball And so no first we injected virus virus To express our voltage sensor in neurons Then we put a small window on a skull to gain an optical access to the neurons We put this animal under the microscope image the neurons. It was actually in sub cortical brain region called stratum It's a region responsible for It's many functions, but one most prominent is local motion So we gained an optical access to stratum. We saw the cells expressing voltage sensor. We make animal run on a ball And while it's running on the ball, we recorded the speed At what animal was running. It was volunteering voluntary motion An image when you runs with a single spike precision After the imaging was done we correlated The speed to the activity of the neurons and we were able to Find that 30 percent of the cells Spike faster when animal is moving And about 10 percent of the cells was spiking slower when animal wasn't moving It gives us an ability when in future for example, we image only neurons And we don't know what animal is doing based on partants of Neuron activity we can say animal was sitting or running. Yeah, so this is kind of a starting point. Yes Reading minds. Okay. Okay. So then just from neural activity You could tell if an animal is running or sitting. Yeah, uh In principle. Yeah, so this is what people right now Trying to do neuroscience. We are obtaining very big very large data sets One of them people doing for zebrafish when we Absorbing zebrafish recording activity of zebrafish during swimming And then using quiz data if you have input activity of the neurons you can tell was animal was zebrafish swimming Or not swimming or doing something else And you can determine that with a very high degree of accuracy if it's swimming or not swimming And probably even predicting speed and direction. Oh, oh, that's cool too. It's a next level So but I would say it's a to certain extent is kind of reading mind. Yeah, so it's kind of Yeah, but uh, of course we We don't use it for reading mind. We're trying to use it to understand how the brain works how the brain works because how do you When can you tell from neural activity if I see the color red or blue? Can you determine from neural activity if I'm happy or sad? So that yes, absolutely So then this is where we want potentially. Yes, so the only one problem in So in a mouse brain It's coming 10 millions or 100 millions of neurons. We were able to image on the 30 up to 30 So you can understand the scale But 30 neurons were able to we were able to tell if it's running or if it's yes stopped Yes, so we were able on a this uh scale already Because it's something very So Many neurons involved in the same But here's a question if I Was wearing an EEG and I was you know, either running on a treadmill Or walking on or imaging that you're running or imagining that I'm running on a treadmill Could you tell the difference in the for EEG? I don't I don't know probably from EEG Yes, because of oscillation that we have neural oscillation. Yes, we can we can say but Neural activity with a single cell and single spike precision Gives much much better Predictive yeah, because you can run and doing something else and EEG may not be able to recognize this So we would like to do complete understanding everything everything Very often we cannot track some very small details of animal is doing so and running is very It's something major going on with animal lots of Neurons involved into this locomotion. So that's why we were able and actually that's why we select this task Because we knew it. This is something that we will be able to find People knew about this kind of effect, but we were able to show it using optical imaging Mm-hmm. Yeah. And so the so Also curious how long the By by using the virus for the implanting the voltage sensors How long did the mice live afterward? We were able to image animals up to half a year Interesting six months half a year about yeah, six months every few weeks. We were able to image Yeah, our best animals Yeah, so like for yeah, yeah, we had actually we had to perfuse them I think we could even image them longer. We had to perfuse them to show the histology for the paper This was the end point Because reviewers ask us oh, can you please show us histology so we really know what are we imaging? Yeah, and so then Would there be a negative Consequence potentially if we were to implant ourselves with the virus. So this is what we still need to understand, but AeV is one of the safest viruses but known safe as our viruses I think but the voltage sensors This is another thing. This is something which we need to study more and assess more Because you said those molecules get into the neurons themselves the membrane Yeah, so but on a positive note on a positive note, uh, I think two years ago Over a year ago fda approved Gen therapy based on a absence for eyes for blindness, I think it's about several hundred thousand Door injection into the eye is that carry av that encodes for options So people can restore some vision I don't know how many people use it, but it this is something that was approved by fda And I didn't think 10 years ago. I couldn't even imagine it would be possible So we don't know what's going to be in another 10 years And how we can advance our our knowledge and our technology in 10 more years Kira, where would the Technology that you've been teaching us where would this take us Translationally in the next couple of decades if we were to be able to unlock this so my biggest scope right now that this technology may allow us to Before new type of experiments that were not possible before To find better understanding of the most of the neurological disease we are going for so It's very interesting if you look if we look back on humankind and we'll one of the most Dramatic change what's happened is a lifespan of humans increased almost twice in the past century right we were living about 40 years now we are going up to 80 years And what we discovered that the longer we live The more diseases we're getting different types of diseases and one of Bad disease what's happening to us. It's a neurological disease Especially after age 60 the probability increases very very Quick and maybe we're getting a little bit longer lifespan, but not always Quality of life Improving so fast And I made my biggest goal and this is what I would like to see happening Using my technology, but we will be able to understand the underlying mechanisms for The neurological disease that we are getting right now and Using this knowledge try to solve how we can treat them because right now there is no basically there is no any treatment for neuro disorders and if there are some we work only partially with lots of lots of side effects And how would your technology enable us to tackle the neurological disease? One of the interesting Thing that We brainstorming a lot and I think we are we're working a little bit right now Uh in 2016 lihe it's I Discovered We published paper in nature in 2016 that if we flicker for a hard slide Into alzheimer mice for several days one hour per day We have amyloid plaque clearing It's just magically amyloid plaque Yeah, they saw reduction up to 50 40 to 50 percent and Very often amyloid plaques associated with alzheimer disease and it's just flashing as in The the 40 horts forced to look at Yeah, so animals are in the cage and there are LEDs that It's flickering at 40 horts For for an hour per day for an hour per day Yeah I wonder if that translates to humans. How do we are we doing any trials with neurological disease? Yeah, so I think we got permission to to do it on humans right now So in a recent paper published in cell we even went a little bit further and we showed it's not only amyloid plaques clearing But also there is restoration of some cognitive abilities This is what more important Which cognitive abilities were restored? So I think it may majorly it's memory memory. So animal I think animals were doing better in the maze. So when we have to get to to find the exit from the maze And animals with a treatment were able to figure out it faster because we remember we remember it's better. Yeah and But nobody understands why and how it's happening Nobody knows where is the treatment? It's like a very big black box. Nobody knows why it's happening And what's our best guess? I don't know and there is some sort of synchronization what I believe and what I saw from some preliminary that I think there is some synchronization of the cells and the synchronization of the cells activates certain mechanisms in the brain that probably activate glia microglia to come and Clean up beta amyloid plaques clearing up of beta amyloid plaques Can restore the better connection between neurons Glia is doing the amyloid plaque Cleaning up. Yeah, some Interesting glial cells are doing the cleanup This is what we think. Yes. We think this is what and I think this is the case Some studies were showing in view of studies. Yeah showing it in real time. And then and then the clearing of the amyloid plaque enables the The circuitry to continue its original Way of retaining really good connectivity and memory Yeah, this is this is what I We hypothesize. Yeah, that's where I think yeah Okay, cool. Okay, so then that's one of the Awesome uses. Yes, and I I believe that if we will be able to see how the neurons synchronized and how the activity The correlation of the activity For example during for a horse flickering and without for a horse flickering less gamia models of mouse We will get a better idea how it works on a functional on a single on a single cell level and we will get some clues on How we can induce it how we make it stronger Or maybe it's too much of flickering is going to be also bad something Yeah, so this is where my biggest goal coming coming from for for this technology. So Our major goal right now is to spread this technology to neuroscience community and everybody to use it To answer the biological questions as gamia is just one example. We're also parking so on. Yes Epilepsy and so on so forth. Yes, which are Tens of millions of people around the world. Yes. Yeah Okay, and then how does the you know, that was on an optogenetics Level of using that technology, but what about the optical voltage? Sensors applied. Do they apply in the same? Uh, how do you how does your virus? Yes? Yeah, it's a very similar molecules. Actually the voltage sensor with We using right now was made out of optogenetic tools we Made them to work in reverse So the sensor that we found was built on optogenetic tools We shine the line and change the voltage, but we make it to work in the reverse Voltage changes in the channel light Voltage changes and then you shine. Yes, and it means that the same principle on how to deliver and how to use it in We were the same as for the genetic tools. Yes Okay, okay because Li-Hue size work is without Yes, it was noninvasive. Absolutely. It was no virus. Yeah. Yeah, no virus. We were Flickering through our eyes non-invasive, but your Virus and yeah, so yeah, what we would like to do we would like using voltage sensor. We would like to See what's going on in the brain when we flickering. Yeah. Yeah, what's going on in the brain? Now you want to add your optical voltage sensors to those experiments. We want to combine it and then see What happens in those action potentials of the specific? Let's say 30 neurons again that you were for example, for example, although we I believe we're gonna push it to 300 Or we are working to push it to on the order of magnitude higher. Yes. Yes, but yes What would you hypothesize that you see? My impression from very preliminary results what I saw I think we will get a synchronization of the cells and most likely this synchronization of a sub threshold level and probably some higher correlation Coherence of single spikes This is what I think we're gonna see but we need to this is just my Coherence and synchronization. Yeah, so single spikes. So we will get Sub threshold oscillation will get more coherent and single spike will will happen At the same timing for multiple neurons same timing for multiple neurons. Okay. Yeah, interesting Wow, and then that could be one of the remedies for neurological disorders is yeah Yeah, yeah, for example, you want to see yes, how fast and why it's happening and what kind of other Other mechanisms triggered by the synchronization Yeah, yeah, our our brain is very synchronizing over many many Brain waves so-called brain waves from alpha to gamma. Yeah, so at every Brain state Characterized by different frequency when we sleep it's one frequency when we think it's different frequency when we walk And so on so forth. So synchronization ensemble synchronization is of a neurons pretty important for Because it's potentially that the that the optogenetics of that of that light that is being shined To clear up the amyloid plaque build up could be A synchronization of a specific one of these maybe an alpha or a it's actually gamma. It's a gamma. It's a gamma Yeah, because it's 40 hertz is gamma interesting. So then we know that it's Potential that's the hypothesis that it's a gamma synchronization that causes the The cleanup of the amyloid plaque and the and kind of the in a sense. It's the restoration to homeostasis From a deteriorated state back Probably potentially. Yeah, it's very exciting. The work is mind blowing. I love it Yeah, so this is my biggest scope and that's I would like to spread the tool and I would be very happy if This molecule my technologies the technologies I'm developing will help in any of these biological questions Yeah, and so the the optical voltage sensors help us be able to measure things like that synchronization Correct. Yes. Yes. Okay. This is what we showed in 30 to potentially up to hopefully 300 neuron soon Versus at an EEG at a at a correct. You can't actually get down to a single neuron level. Yeah and it's it's we're getting Qualitatively different information from From EEG and from voltage sensors and and because those voltage sensors have the fluorescent protein you can View that the action potentials. We can even tell in the dendrites from what dendrite it comes to a soma What we can resolve especially from which dendrite even we come we can see it's where it comes from. Yes Where it comes from because imaging happening On kilohertz frequencies kilohertz frequencies Yeah And uh, yeah If we can even say see how it's originating in the dendrites propagate to a soma gets it action potential yeah So people before were able to do this kind of experiments only in Culture primary culture itself and this is not relevant because culture results. We don't do anything We're not connected to a function to behavioral And when we can connect it to the behavior in view of this is where we've found stuff starts Oh my gosh. Yeah. Okay. So then what does it to co okay So then that's back to the whole running versus walking Okay, or potentially the happy or sad Okay. Okay. It seems like if we were in a gamma synchrony that it would be a state of of Of really Of blister transcendence or so. No, so not necessarily So, okay, usually when we focused when we think this is where we see gamma gamma bent But that's like really deep flow states, right? Yeah, so and also Yeah, we have multiple different brain regions and different brain region Prefer different bands at different time. Yes Okay. Okay. This is another thing. Yeah, so it can be a mixture of multiple. It can be alpha over beta on Gamma Yeah, but what we say is we also talk about power of each band in isolation Okay more Yeah, more for another time because yeah, there's so much to sell unpack about what you're doing It's also crazy that you are You know, you want to take these tools and you want to spread them around the world and we want to get them in the hands of You know 12 16 18 19 year olds get them in the hands of young people to be able to go with their own creative thinking and Build. Oh, yeah But at the same time you're leaving the Cambridge area And you're planning to go to Westlake University in China on a tenure track To be an assistant professor in the school of life sciences and Hangzhou. Yeah, so I decided to accept an offer from Westlake University starting sometimes later this year because it's given me A great opportunity to pursue my dreams on my own I think I feel very grateful to add for this six years with him Where I mature as a scientist now I feel much more confident going and doing my science the science on my own and I decided to accept offer because it gives me a great opportunity To pursue these dreams In in science because we we basically giving me freedom you do whatever you want as long as it's impactful And this is my dream. I want to do whatever I want. Maybe tomorrow I will change my mind completely or do something else As long as it's impactful. Yeah So, yeah, I will be moving to to china shortly It wasn't maybe always a very simple decision and choice for me. Yeah, but uh, I just want to change my dream I want to change my dream And there's no way to chase it near the other cluster of people in Cambridge. Unfortunately, I Couldn't get any offers All matching offers from united yeah for from united states and I would like to stay in academia So this is my dream. This is another thing that I would like to Be in academia because I believe academia is a unique again unique place would give you a complete freedom of your creativity Yes, yes, this is when you can change. Whatever you're going to be doing in one day I've been working in industry and it's very different philosophy in industry very different approach and I can tell This is not something that fits me hundred percent. Yes. Yes Maybe there are different benefits. We're on the side of salaries and so on so forth, but I for me it's more important to have is but I can As we discussed in the beginning can cover my potential in this kind of creativity I would even curiosity Yes, I would Yeah, with the resources I would figure out how to keep you in the Cambridge area Yeah, thank you. Yeah, because you are a very eloquent communicator and a great scientist And so I think it's very important to keep you Around and be able to help So I think nowadays science is and I should and I think science should be very international Because when I develop something when I Create something I would like it to be open to anybody to everybody anywhere And and no matter what you do no matter where you live and no matter How you think I wanted if you want to I wanted to be freely Uh accessible to everyone and the ideas and the Other like data I wanted to be Totally open to public. Yeah, the open notebook science is a very important part of being able to push the edge of knowledge together as a society More freely and get the technologies down to the young people to be able to play with and use the tools Rather than keeping it closed off For monetary yeah because Technology shapes our civilization the faster we can apply this technology where more people can use it the better I think the more positive changes we can see. Yeah. Yeah Yeah, it's so It's tough because you know, it's like a you know, your wife is also Chinese which makes this transition a little bit easier. Uh, yeah, I hope I will get more support Yeah, yeah on this end and it's a beautiful Facility we were looking at it a little bit before we started in and uh And it's good that you'll be in the school of life sciences. You'll be pursuing You know, you'll be teaching other people around the world. You'll be learning about the Chinese culture more Um, and hopefully we can work on as we say being this bridge, you know, I can look at this very positively too I can say it's a very good thing that you're going because now This one of the missions that I say is that I want to help be a bridge between the united states and china I want to help really foster a bridge to that like open notebook science that collaboration because I think that if the united states and china Work together. I think we can Help make sure the rest of the world. We don't have any we can mitigate the existential risks if we work together So maybe we can do cool things like go out to west like potentially and we'll be great and interview We are stronger when we are together. They were much stronger together and I believe there are many great people in west like Who you would like to talk to definitely. Yeah, correct. Yeah, and that's such a beautiful part of the world Just very close to shanghai Right there on pacific ocean. There's so much to explore so many brilliant people in china that are pushing the edge Yeah, I I I feel like a trip We've mentioned this so many times a trip to china to interview some of the world leading scientists Would it be so important to do so? I'm really looking forward to that and also think about that on the channel being able to have a series of 30 interviews with not white You know people people from asia from china specifically is very important because then we understand that It doesn't matter if it's black white purple brown. Does it matter? I believe when we Working together in a very diverse community. This is when the most part of things happening. I think our Creativity the synergy of this creativity when the diverse group is from different backgrounds working together Yeah, yeah, because then you realize what someone from a From the eastern civilizations Is thinking about what a western organization is trying to do and you get maybe they can actually better The idea maybe someone from the west can better one of the ideas from the east So there's ways to like collaborate on this maybe someone fresh from a philosophy in africa or from latin america can Come in and give you some profound insight into your academia or your industry or your governmental structures And so I I completely agree that it's a very beautiful thing to be able to work that way But also on meritocracy at the same time. It's a it's an interesting conversational point Okay, just to wrap a couple quick things This was I found very interesting. We've now interviewed. I believe, you know, abri de gray Robert a gem yarn There's a couple other people that don't have cell phones Yeah, so I we we now know a decent amount of scientists That choose to not have cell phones because they believe it's destroyer of of personal solitude of focus So what is the reason why you choose to not have a cell phone? So for me, first of all, it's a destruction Destruction if I have a cell phone it can be destruction when it's ringing or if it's in my pocket, I will be Sometimes unintentionally for example pulling in and staring at it for no reason. So My observation and it's also some sort of a protest To to what I see outside. So when I take in a train what I do on a train I count people On a train who using cell phones versus who are not using cell phones And tell us the numbers so 80 percent in Cambridge on a red line I'm taking the red line most of time using a cell phone. What do you do? We're staring at it like this. Yeah, and uh, I I feel sometimes this is a crazy number This is a very big number and I I am afraid one day people will wear goggles All the time are we not going to see people around? Yeah, and I think cell phones They are useful But we're also destroying some of our Like what who we really are because communication I prefer communication in torsons me too. I prefer communication in torsons. This is I think It's very different experience. So this is another thing When I don't have a cell phone and people want to talk to me. We will come and talk to me in torsons. So promoting this Communication in person. So and on a relevant note observation. For example, I've been in in Tokyo just recently taken train in Tokyo And I also was counting people using a cell phone wear and It was less no more than 10 percent on a tokyo subway system Only 10 percent versus 80 percent. Yeah japanese for some reason. This is my observation We don't we we don't use cell phone on a train and we don't talk on a cell phone on the train And then I few weeks later. I was in China in China is very different situation Without cell phone, you won't be able to do anything There is a street food. I believe people selling a food with we just cook at home Couple of minutes ago. You won't be able to buy a food on the streets because it's ollie payer. We yeah So you use you scan a qr code and they give you a food Nobody use cash when they pull out the cash, but they were looking at me. What is this cash weird? Yes, that you're just scanning your qr qr code. You're taking taxi you're paying in a in a store you're paying in the restaurant with a With a phone. So it's With Phone in China integrated in daily life much more than here and this is another my fear. Okay. I will have to use a cell phone if I go Or Because I won't be able to survive or this is I will I will be pushed to extreme when Without cell phone. I won't be able to function well or you could do something like only Download the payment Yeah, and then only take it with you when you leave the campus. Yeah, so that yeah Because then if you're spending your time on the campus, I know. Wow. So it's almost as though We're some of the civilization Is forcing you to have the device in order to interact with people. Yes and uh, I also when I what I when I It maybe it's not very good, but I also try to see what people doing convert Cell phones during when they're taking train or something. Oh, yeah, I do too when I I was when we were in the There was a Venetian plaza and there was a big Musical Group playing young girls on their phones and the instrumentalists right in front of them But they're right there on their phones and I look and they're you know doing that some game where they're you know And just about 50 percent of people playing game from my observation 50 percent just playing games playing Puzzles or some sort of games when you have to do something. Yes. Yes. Yes. This my observation Some cases when people are just sliding screens back and forth So and I'm when I'm looking I I'm afraid. Well, okay I'm afraid but I will be doing if I have a phone I will be doing something similar and I think it's very bad This way this is another way And you have people like me that see what you see and then I just went and deleted all of my social media apps I turned off all of my notifications. My phone is always on silent So it's just Just call email text and like maps and uber and stuff like that, right? Something practical, but even the practicality even that the notifications are off. The phone is always on silent So I have to go with my own instinct to go and open the messages to go look but not Me getting sucked in to to go. Yeah, so this is one of uh, I think Two years ago international health organization classified a Game dependence Depends on from video games as a disorder. They put it in a in a list of official disorders And they also think that When people checking phones were often very often 150 times a day. Yeah, all right. Yeah, so this is also They think this is already out of a normal Range and I'm afraid but it might affect me in a bad way as well Just there's no way it wouldn't yeah, so it will it's just up to you to take control of it Instead of it controlling you So yeah, this is a very interesting conversational point that you and I could continue riffing on But even just having your perspective on why you don't have one is is so so critical, right? It's you're fighting against in so many ways the cultural norm. I love that. I do it too Okay, a couple quick things on the way out What is one skill? That you think that young people and even adults should know moving into the exponential technology age Are you into exponential technology age? Well, this is a tough question one skill I think it doesn't so My my perspective on I think it doesn't matter how smart we are Doesn't matter how cool and how advanced technologically we are I think first of all, we should stay kind to each other. Yeah, doesn't matter how smart you are if you're not kind Nobody gonna deal with you. I think People should still remember about moral standards be nice to each other and of course love each other This is I think this is the most important thing if we do this over as we can figure out Yeah, but sometimes this is much harder to figure out when any science when any Any technological challenge ever unfortunately, yeah, yeah and things like the ancient multi-thousand-year-old traditions of meditation and connectedness to You know spiritual transcendence they can help us with our ability to be kind and compassionate to one another and Yeah, this is I'm afraid maybe we in our modern society we start towards increased kind of things And it might have to do with the sense the industrial revolution the Just everything having to be productive Capitalism efficient has to make money And yeah, and that has made us In a sense, it's made us more part of the economic machinery Than it has made us spiritually enlightened He gives us fills it away from nature. Yeah into the metropolis is of And all of the monolithic buildings without atriums and without plant gardens and rock walls and fun In animal therapy with the forest therapy, you know together Okay, and the last two questions is Are we in the simulation? Ah, so this is If we are in the simulation Very recently, I think Scientists from israel published the work showing that if we in simulation The computer power that needs to create the simulation Requires more molecule and more atoms when currently I in the universe So it means it should be universe with Several times bigger than current universe in order to do the simulations We predict they say, okay If in the simple terms If there is one particle and we would like to predict its motion We will need the computation power that would require at least three particles You know, so and this is how we're showing. Okay, probably we are not in the simulation But we are in the simulation in a way that everything we see feel and do this is This is happening through our interaction Through the neurons, right This is in our mind only what we see feel and do this is only in our mind and our mind simulates this picture So it's yes and no in the same time Yes and no in the same time Yeah, we've we've heard it a couple times that That the experiences are Right here inside of our skull and then we create that and on the other point The rendering aspect is kind of interesting that You are just rendering what you see In experience so that you are not rendering anything else Except this room in MIT right now. Yeah, and then once you go out, then you start rendering the other things which saves on that computational Absolutely power side of things So there's a couple ways to yeah to poke and prod at this scientifically that I'm very interested in last question What is the most beautiful thing in the world? Humans I still believe humans. I still believe humans Yeah, because and this is what we starting we starting ourselves because we believe probably some was we don't think like After medieval renaissance started and renaissance started because people start talking on themselves Start exploring themselves That was prohibited by church for so many centuries And that's why we starting the brain one of the most beautiful part of our body Yeah, so probably this yeah Yeah, and there's currently eight billion different Everybody unique everybody special special and unique and have their own creative potential that can be flourished and A hundred billion before the eight billion that built the beautiful civilization that we have Yeah Wow, Kirill. Wow. Wow. Wow. This has been such a fascinating show. Thank you. Thank you very much. Thank you for coming here It was such an honor It was such an honor and we learned a ton from this show optical voltage sensors Optogenetics expansion microscopy all these new novel tools and methods for imaging and interfacing And just what's actually at the edge and how do we get that edge? Back down to the general population to get using it. This has been super fascinating. Thanks everyone for tuning in We greatly appreciate it go and share more conversations around neural imaging and interfacing with your friends your family Your co-workers on social media start sharing and talking about these conversations more Give us your thoughts in the comments below. Check out Kirill's links below as well in the bio Also support the artists the entrepreneurs the organizations around the world that you believe in We had a part of our conversation was about the united states working together with china's figure out Who these people are across the seas that we can work with and collaborate with that are building really important Platforms that bring us together and help us work together So support them support simulation our links are below as well support us So we can keep doing cool things like going to westlake university and conducting some of these interviews that would be fascinating And go and build the future everyone manifest your dreams into the world Thank you so much for tuning in and we will see you soon peace Bye That was so good. You are awesome