[00:00] I got a faculty position at UC Berkeley two years ago and now I raised about six million [00:06] in the first two years of my faculty job. [00:12] So my dream, I have many dreams, but my main dream was to build a new life form. [00:19] When I encountered death and sickness in my family, I thought could we build a biology [00:27] where we don't have to die, where we can upgrade parts of our body on the fly and live happier [00:33] and healthier. [00:36] And of course, it's very hard to find this idea, especially if you're an undergrad or [00:41] a graduate student. [00:42] So I did my undergrad in chemistry, my PhD is in chemistry too. [00:48] I grew up in Russia and of course, funding is not that great, political situation not [00:53] So I'm here just across the bridge from San Francisco. [00:59] And I have a lab now about 20 people. [01:02] And so the goal of our lab is to fit this entire Intel factory into a test tube. [01:12] It's not even molecular printer. [01:14] So actually, maybe printer is not required. [01:18] You can just build an information into components. [01:21] And if you look at how nanoscale devices are built these days, through top down approach, [01:29] which is probably the most sophisticated technology that humanity ever developed. [01:35] And that's part of many, many devices that we use every day, like computer chips, microfluidics, [01:44] optical interconnects. [01:47] But it's somewhat inflexible approach. [01:50] And if you know the cost of the most recent asml tool that allows you to do extreme UV [01:55] lithography is about $500 million. [01:59] And that's many companies like Intel, Samsung already bought five of them, even though only [02:05] one was built so far. [02:08] And if you look at this Intel factory and the devices that manufactured there, you can [02:16] see if you zoom in that they're not super precise. [02:21] But if you zoom in on the Pond scum near the parking lot of this Intel factory, you can [02:29] find a totally different approach to nanofabrication, namely bottom up self assembly. [02:36] A single bacterium about one micron in size can make billions of different biomolecules [02:44] in a scalable fashion and with much higher precision. [02:48] For example, every ATPase in our body is made of exactly the same number of atoms, [02:54] atomically precise manufacturing. [02:57] And many of you mentioned it today. [02:59] Moreover, this molecular devices, structures can exhibit behavior, complex behavior when [03:09] the potential across the membrane increases. [03:11] This molecular rotor rotates at different speed. [03:18] And so my dream in high school was to maybe take this biological components and try to [03:25] build a new life form where we build things in a more rational way. [03:32] Because if you now try to disrupt this biological system, like for example, I want to change [03:42] the electric property refractive index of alpha crystalline, which is a component of OI. [03:49] Unfortunately, I can cause a cancer too, because it's this alpha crystalline is a [03:55] component of many metabolic pathways. [03:58] And so you cannot just take it out slightly change it. [04:03] It changes the whole pathway. [04:05] So I turned to engineering and I'm an engineering professor at Berkeley. [04:11] And there, what I like is a modular approach where you can take transistor, resistor and [04:19] capacitor, put them together in a very complex integrated circuits and build machines, devices [04:26] that challenge complexity of a human brain in many ways outperform it. [04:32] Yeah, well, maybe not for much longer. [04:35] We we can outperform human brain completely. [04:42] But if you look at the natural designs, there are many really bad designs. [04:46] We eat and breathe through the same passageway, major choking hazard. [04:50] You probably can come up with some other examples. [04:55] Anybody, bad designs in your body in nature? [04:58] Yeah, blind spot in the eye, Christine says. [05:03] Yes. [05:04] What? [05:10] Good way to put it. [05:12] So the sloyringial nerve that I used to speak to you right now, that's two feet of wasted [05:17] wiring, right? [05:18] Just because we evolved from fish. [05:20] You know, as an engineer, you would just nip it, reconnect at the top. [05:23] But since we evolved from fish, it's not possible. [05:26] Nano scale, rubisco is the laziest possible enzyme. [05:31] Typically, enzymes convert thousands of molecules per minute, per second. [05:36] Rubisco makes maybe two molecules of oxygen from CO2. [05:41] Sometimes it grabs oxygen and burns glucose. [05:45] So I said, could we maybe combine the strengths of rational top-down engineering of, [05:52] let's say, electrical engineering, nanofabrication, and bottom-up self-assembly, [05:59] something like this, to build a new nanotechnology. [06:05] And I think it's possible. [06:07] And I'm not sure what's the best technology, but what I'm using right now is DNA nanotechnology. [06:12] And many of you know what DNA is, stack of bases, very simple rules, ATGC. [06:18] You can consider it one and zero. [06:20] And you can use those rules to build very complex molecules like DNA origami [06:27] that Adam and some other people already referred to. [06:31] It's really an amazing process that allows you to assemble, for example, this. [06:37] So you use ATGC to bring this long black scaffold together with a bunch of synthetic DNA strands. [06:47] And they'll magically assemble into a structure like this smiley face [06:52] or map of North America. [06:53] So basically, it's kind of 2D positioning, no printer required. [07:00] So what's revolutionary here is you suddenly doubt molecules with the programming language. [07:06] By programming sequence of these molecules, you can make them fold into any shapes. [07:13] And I have to say, go Beres, because I'm from Berkeley. [07:18] And so single DNA origami, it's about 100 by 100 nanometers, [07:23] and it's big enough to make a single transistor. [07:26] But if you want to make something more complex like this photoreceptor circuit, [07:30] we need a much larger breadboard, one minute left. [07:33] So I'm going to tell you a bit my work as a postdoc. [07:38] I tried to make a single DNA origami. [07:41] Postdoc, I tried to make nanoscale monoliths. [07:47] And it's not Da Vinci, but we can make trillions of this in a test tube. [07:52] It's atomic force microscope. [07:55] And I'm just going to quickly switch to tell you what my lab is doing right now. [08:01] We're trying to bring in materials with interest in physics and use DNA as information bearing molecule. [08:08] So you can see it's kind of 3D printing. [08:11] But in a massively parallel way. [08:13] And there is always the question, what's the first killer app? [08:16] What would convince this country or bigger scientific community to invest more money? [08:24] We're not competing with Russia to go to the moon. [08:28] We're trying to spend taxpayers' money in a sensible way to cure cancer [08:33] or build some devices that can make profit. [08:36] So one of these devices is a bear filter. [08:40] You all have it in your cameras. [08:41] That kind of allows us to analyze RGB components because you only have three cones in your eye. [08:49] And so we can assemble this structure in 3D by encoding DNA. [08:57] By endowing two dielectrics, you only need two different materials. [09:00] Let's say silicon oxide and titanium dioxide. [09:03] And just need to attach DNA strands in precise position [09:07] to make them self-assemble into these complex structures. [09:11] And we do inverse electromagnetic designs, design software for DNA structure design. [09:18] And we self-assemble them. [09:20] And this is an example of how this kind of 3D printer, but a scalable 3D printer, [09:28] that would allow you to make billions of devices [09:30] so you can satisfy demands of humanity for this particular component quickly. [09:37] And as a very first PhD student who joined my lab, he played hockey for MIT. [09:45] And he got concussion. [09:47] And since then, he got interested in neurodegenerative diseases. [09:53] And so he wanted to find a way to read out single neuron activity with millisecond resolution. [10:02] But we cannot use optogenetics. [10:05] Many of you know optogenetics. [10:07] So typically right now it's done by drilling a hole. [10:11] So that's electrochemical readout, electrical readout. [10:14] You drill a hole and you insert this neuropixel electrode [10:20] that can at most read out 200 neurons at the same time. [10:25] So he is now developing a way to read out many more neurons in a non-invasive way [10:31] that uses magnetic field that, of course, can go very well through the skull. [10:37] And this, let me conclude because Alison is looking at me. [10:49] Yeah, this is my lab. [10:52] Thank you. [10:57] Yeah, Durham. [10:59] Okay, questions, comments? [11:01] Maybe if number one. [11:03] I will leave it to the, yeah. [11:07] Well. [11:09] So interesting talk. [11:10] The DNA kind of matching. [11:12] So you're using the complementarity of DNA as the main kind of organizational tool. [11:18] But of course, in biology, so DNA has multiple levels of organization, [11:22] epigenetics essentially. [11:23] So you can have small scale around a histone or you can have macro domains and such. [11:30] So has any of that been explored in kind of the evolved kind of macro assembly properties [11:36] or is it still right now just the small scale interaction that's still being used? [11:40] Yeah, great question. [11:41] We also use multiple scales. [11:44] We do things in a hierarchical way. [11:47] So ideally what you want to do is to mix thousands of components and they recognize each other. [11:54] But turns out the yields are pretty low. [11:57] So what we eventually ended up using is you make a system that, for example, [12:03] assembles from four building blocks into one building block. [12:07] You use four of those bigger building blocks to make even bigger and so on. [12:12] So called fractal or hierarchical assembly. [12:15] And our body is actually hierarchical. [12:16] We go from molecules to cells to tissues to organs. [12:22] What is guiding the larger scale interactions though? [12:25] I mean fractal, yeah, you just repeat the pattern over and over again. [12:28] But what is there a greater kind of than interaction? [12:31] Yeah, we try to keep the same rules. [12:34] We use DNA sticky ends only for each step. [12:37] Okay, it's still the sticky end. [12:38] It's the sequence of ETGCs. [12:42] Thank you so much.