The researchers also evolved a transcription factor with AND-gate behavior: its output required both a light signal and a chemical signal. This connects protein engineering with the idea of biological computation, where combinations of inputs determine an outcome. The demonstration is a controllable molecular logic function, not evidence of an instantaneous or general-purpose cellular computer.
1,328 words · auto-generated from the episode video
42:55>> Well, actually, >> yeah, biology is not like physics that way. >> But that's a really interesting point. Again, this and the tracing of the process to the root to the first principle and the why then allows you to make more calculated choices about how do you want to intervene or or interact with the system >> to to to decrease the external as much as much external disruption as possible. >> Exactly. Exactly. >> This is that's that's and the journey to get there. >> Very clever. >> Yeah. Yeah. And finally, Breakthrough. I think this is going to be your favorite. >> Oh my god. No, there's another one. Yes. >> Okay. So, just a really good So, the break breakthrough number one. So, >> breakthrough number one was we made the
43:35blue light sensitive protein >> sensitive to >> multiple um >> green light >> green light >> which was good because now and also in later we can we can be sensitive to to multiple >> right >> here >> then now we figured out the the the red light trash collector piece >> uh with the the rale scattering. >> Yes. >> And now there's the last one is single protein computers. Okay. >> Okay. >> Right. >> We are now trying to create an andgate. >> Okay. All the students of logic know about the and statement. Right. I need both of my inputs to be >> No, no, no. I need either of my input zero or one to be one and I'll get um
44:18>> am I showing No, I'm showing uh this is this is a orgate. Okay guys, whoever's whoever is looking at the uh um thing, this is like a not and gate, right? Because the A and B if they're one, this the output is zero. >> So this is a NAND gate. >> Yes. Yes. >> Sorry that that's my fault. Okay. But in any case, an ANDgate is when both the inputs are one and that's when the output is one. Otherwise, it's always zero. >> Right. Right. Right. Okay. >> Which the idea is like Yeah. >> This and that are true. That means that means the total thing is true and prosper. Yes. Okay. So historically biological logic circuits we can construct them but usually what they require is a multi-gene cascading
44:59process meaning gene A is on and gene B is on which means that gene C will be on okay so it requires this and that to be on and both of them go and become that I'd like all of this to be in a single protein right okay because that way it's not a slow I don't have to wait for one gene to turn on another gene and another gene >> it's not a sequential process it's becomes just an instantaneous Boom. It's this protein, right? And um it's not also resource intensive because to transcribe one gene, it's a lot of ATP. To transcribe another gene, again, a lot of energy. And so what I want is a single protein advantage. The computation is instantaneous. >> Yeah. >> Right. >> And there's negligible
45:39>> metabolic load. Yeah. >> So what do I do? I use my TT on and T off system. This is something that we have discussed in the um it was the time capsule. >> Oh, one of my favorite. That one was so Yeah, that was that was a crazy episode. >> That was a great If you guys have not watched that episode, I think I put that in my favorites list for last year. >> Very fresh. >> No, that that was this year. Wait, the Oh, I'm thinking about I'm I'm confusing time uh time crystals and the and the >> and this is the time capsule, the honeycomb structure. >> Yeah, that one was also really good. But the idea is with with um RTA, this is this TET on Tet off system. Basically, whenever there's doxycyc
46:19>> Mhm. this um particular >> that's right >> protein is going to get transcribed the gene is going to get transcribed and so what they did was they combined this teton system the RTA with something called a pest deg
46:41rapid destruction okay so here's what I've done I've created um a protein where if I at doxycycan it's going to come on >> yes >> but as soon as it gets transcribed part of it has this degon system to degrade it's like a degrade flag the proteosome is going to come in and degrade it >> okay so it's only going to be transiently active for a very short amount of time okay >> now instead of being a continuous on and off like a continuous thing that is either in an on or off state now you're kind of gating it to a a a window of time that has an explicit start and explicit end. >> Exactly. And so here is why the logic
47:23works because it requires input A which is transcription on from the light that I'm getting. >> Yes. >> And input B. >> Doxycycling needs to be present. >> Okay. Both need to be present and they need to outpace the degradation. >> Okay. If I turn off input >> Mhm. >> then the whatever protein is still there is going to get degraded immediately. So now it's a super time sensitive >> and switch. >> Yes. Yes. Yes. Does that make sense? Yeah, it does. It does. It does. >> It needs the and of the of the light and the doxy if both of And the light I can trigger immediately, right? The doxy can sort of just hang out, >> right? >> But the light I can now trigger
48:03immediately and turn off and as soon as I turn off it gets degraded. >> The the light is our controller. The the doxycyc is a part of the substrate that's necessary to facilitate the environment where we have control. But we don't necessarily as long as the doxy's present. >> Yes. >> That's the only that's the thing that matters. >> Exactly. And and they were able to actually do this. They were able to actually create this and switch in a single protein. Now just imagine right like computers are based on logic on computational logic. And here we're able to do computational logic with a single protein at like the second time scale resolution, right? It
48:44just it just opens up a lot of really cool avenues for biomedical research, for fundamental science research because now if we want to figure out what this particular gene does, we can use this andgate to be like, well, >> what is the logic of this particular gene in relation to the entire logic table of the rest of the >> genome? I is. So would you say there are a lot of ways you could utilize it is one way you could utilize it as basically uh being able to isolate in a very complex biological environment certain things you want to look at and control it so that you can watch the process or the outcomes knowing what the
49:25in like knowing that you're controlling like the inputs into the system. >> Exactly. Yeah. Exactly. And from that we can as I said like create the logic table and that really lets us understand how genes relate to one another how they relate to external stimuli >> right >> like all sorts of stuff right and the idea is with this opto evolution we can now create proteins that have this dynamic behavior >> that need and that are not always one >> this is a logic this is this is one that requires inputs to turn on >> which which means then you could then
Molecular BiologyProtein EngineeringSynthetic BiologyBioengineering