| --- Day changed Fri Jun 06 2008 | ||
| kanzure | http://heybryan.org/pipermail/synth2008/2008-June/thread.html Lab team :) | 01:17 |
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| Vedestin | http://www.newcastle.edu.au/program/undergraduate/2008/10981.html | 10:52 |
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| kanzure | Vedestin: hm? | 11:14 |
| Vedestin | looking at a few degree programs available to me | 11:14 |
| Vedestin | this looks pretty interesting too http://www.newcastle.edu.au/program/undergraduate/2008/10986.html | 11:16 |
| Vedestin | did you settle on a degree + university yet, kanzure? | 11:20 |
| kanzure | Vedestin: Not quite yet. I have it all narrowed down, of course, but I'm still trying to get them to agree to a double major. | 11:21 |
| Vedestin | your parents? or the university? | 11:21 |
| kanzure | The university. | 11:34 |
| Vedestin | in computer science and neuroscience? | 11:41 |
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| kanzure | No. | 11:47 |
| Vedestin | still on the engineering path then? | 12:00 |
| kanzure | sort of :) | 12:02 |
| kanzure | I'm trying to do computational/science + manufacturing. | 12:02 |
| Vedestin | ahh ok | 12:06 |
| Vedestin | that sounds pretty interesting | 12:08 |
| Vedestin | doing that hear would be a double degree | 12:08 |
| Vedestin | rather than a double major | 12:08 |
| Vedestin | lol @ hear | 12:10 |
| Vedestin | can you tell it's 2am? | 12:10 |
| kanzure | the terminology doesn't make sense anyway | 12:57 |
| Vedestin | which? | 13:00 |
| kanzure | double degree / double major stuff | 13:17 |
| kanzure | it's probably because the idea of a 'major' (specialization for a piece of paper) is odd | 13:17 |
| kanzure | fenn: So let's just say that I have four polymerase molecules that selectively incorporate a different nucleotide. One does adenosine, the other does thymine, etc. It turns out that the requisite mutations are highly localized to a particular amino acid on a loop in the protein. | 13:17 |
| kanzure | Now what? I'm thinking of trying to have all four of these polymerases 'combined' into one where we can switch the functionality. | 13:18 |
| kanzure | for example, in pH of xyz, it's in mode #1, in pH of something else it's in mode #2, etc. | 13:18 |
| kanzure | That sort of thing. But it may turn out that the amino acid substitutions are vastly different. If it's a single atom change or something, what could we do with that? | 13:18 |
| Vedestin | the way it works here is that there's more credit in a double degree than a double major, double major in science would still be 240 credit points, 3 years, while a double degree is 400 points, 5 years | 13:19 |
| Vedestin | and you have BSc and BEng at the end | 13:20 |
| Vedestin | not just one or the other | 13:20 |
| Vedestin | but sorry, go back to your polymerase | 13:20 |
| kanzure | hm | 13:21 |
| kanzure | maybe it would be possible to use four different polymerases, and have them re-attach and scan the length of the already constructed DNA molecules ? | 13:22 |
| fenn | perhaps you could separate the polymerase into two chunks, one chunk that always stays on the strand (placeholder) and another chunk that floats around and can detach/reattach | 13:24 |
| fenn | i dont think its going to be as simple as finding the right amino acid to use | 13:25 |
| ybit | if we can transfer the contents of the brain, we may be able to forgo the current longevity model produced by sens | 14:29 |
| ybit | but how to do this is beyond me right now : | 14:29 |
| ybit | | | 14:29 |
| ybit | .. | 14:29 |
| fenn | kurzweil nanobot 'gradual upload' sounds like a pretty good start | 14:30 |
| ybit | i was thinking of a similiar concept earlier | 14:30 |
| ybit | is this mentioned in his book? | 14:31 |
| fenn | dunno i dont think i've read his books | 14:31 |
| fenn | actually it might have been moravec who came up with the idea | 14:31 |
| fenn | ybit: ever heard of the 'god helmet'? | 14:33 |
| ybit | i have not | 14:33 |
| ybit | wikipedia is telling me all about it though :) | 14:34 |
| ybit | ah, i have heard of this, but not the term | 14:34 |
| ybit | fenn: you wouldn't happen to have a link to lit. on the gradual uploading to nanobots? | 14:37 |
| ybit | after reading it, i haven't heard of the experiment.. i thought it was about to refer to experiments dealing with magnetism and memory | 14:39 |
| fenn | the 'god helmet' is something like rTMS but without all the high power capacitor discharge stuff | 14:39 |
| kanzure | fenn: re: two chunks. check out 'beta clamp'. it's like an anchor on DNA for polymerase. it's a module. | 14:39 |
| fenn | so its something you can actually play with.. there is some site that sells electronics that hook up to your sound card | 14:40 |
| kanzure | then we can have four different types of polymerases swimming around | 14:40 |
| fenn | sweet | 14:40 |
| kanzure | re: mind uploading, check out Joe Stoel or osmething and 'mind uploading action group' | 14:40 |
| kanzure | yeah, so that sounds better | 14:40 |
| kanzure | now I'm thinking about the painful selection experiment | 14:40 |
| fenn | mind uploading research group? | 14:41 |
| kanzure | yep, it was a 'task force' that randomly converged on the internet in the late 90s | 14:42 |
| kanzure | apparently they were working on nematode neuronal uploading | 14:42 |
| kanzure | I don't know what they actually /did/ | 14:42 |
| kanzure | but I guess they could have had a slice-and-scan setup | 14:42 |
| fenn | yep, looks pretty fancy: http://minduploading.org/research.html | 14:44 |
| kanzure | woah | 14:46 |
| * kanzure regrets not seeing that sooner. | 14:46 | |
| kanzure | led by Eugene Leitl | 14:47 |
| kanzure | http://eugen.leitl.org/ | 14:47 |
| fenn | yeah. leitl quote that reminds me of the DNA-FPGA idea: " It occured to me that one could create engineered proteins which precipitate nanocircuitry within/around neurons, which could be capable of emulating that particular neuron's function, after the original is defunct." | 14:48 |
| fenn | so you just need to infect all the brain cells with some vector that expresses carbon nanotubes.. hrm :) | 14:49 |
| fenn | " soon, organ banks can actually start banking organs." wow someone's really blowing it | 14:52 |
| kanzure | dunno if you need CNTs | 14:53 |
| fenn | well, some kind of semiconductor | 14:53 |
| kanzure | but Winfree's sierpenski triangles might help | 14:53 |
| fenn | CNT's work better at small scales, so i hear | 14:53 |
| fenn | or graphene, same thing really | 14:53 |
| kanzure | I have a new contact who works in CNTs, he's very eager to help | 14:53 |
| kanzure | he also has ridiculously large machines and free access to | 14:53 |
| fenn | machine = computer? | 14:54 |
| kanzure | machine = make CNTs, has SEMs, all sorts of fun stuff | 14:57 |
| kanzure | now then ... I'm not so sure about the prospects of proteins to replace neurons | 14:58 |
| kanzure | since there's a lot of functionality that you're going to kind of miss, I think | 14:58 |
| kanzure | neuron-by-neuron nanotech replacement therapies have been recommended before, but that requires nanotech | 14:58 |
| fenn | right | 14:58 |
| kanzure | also, on an unrelated note, brain cancer sucks | 14:59 |
| kanzure | that's the one remaining cancer that we can't really do much about, if you have a giant tumor deep inside there you're not going to be able to do much | 14:59 |
| kanzure | (although with the nanoparticle delivery system, something might happen sure, but whatever) | 14:59 |
| kanzure | anyway, my point is that there might be a system to fix this | 14:59 |
| kanzure | if we can harness neurogenesis | 14:59 |
| fenn | to fix what? | 14:59 |
| kanzure | and specifically lesion parts of the brain that develop either (1) tumors or (2) some sort of uber-degenerative issue | 15:00 |
| kanzure | so you lesion it, clean it up, and then have neurogenesis to fill in the gaps again with the same basic circuitry (fit to that part of the brain) | 15:00 |
| kanzure | this doesn't recover the old data | 15:00 |
| kanzure | the old data was degrading and was lost by that point | 15:00 |
| fenn | you'd have to have a way to 'download' the data anyway | 15:00 |
| fenn | as well as a way to upload | 15:01 |
| fenn | might as well grow a neuropod and transplant it :P | 15:01 |
| kanzure | ok, so for preventive measures | 15:01 |
| kanzure | to make sure you don't lose the data | 15:01 |
| kanzure | backups, backups, backups | 15:01 |
| fenn | weekly backups are always a good idea | 15:01 |
| kanzure | nightly | 15:01 |
| fenn | if you are being persecuted, sure | 15:01 |
| kanzure | so | 15:02 |
| fenn | a week of boring nothingness might actually be fun to untangle | 15:02 |
| kanzure | to do backups | 15:02 |
| kanzure | Keith F. Lynch once gave me a good nanotech idea | 15:02 |
| kanzure | the idea was to have nanotech go in and report the connections between each other via encodings into organic molecules | 15:02 |
| kanzure | and then this data is stored and you piss it out | 15:02 |
| kanzure | and then you go read the molecules at some later time | 15:03 |
| kanzure | however, that requires nanotech. | 15:03 |
| kanzure | an interesting alternative might be to make the neurons do self-diagnosis of that sort | 15:03 |
| kanzure | the big issue is getting separate ID schemes going on or something | 15:03 |
| kanzure | there's no way you can coordinate that many ID molecules | 15:03 |
| kanzure | you'd have to be able to generate 64bit ID molecules or something | 15:03 |
| kanzure | and to have them be persistent and so on? yikes | 15:03 |
| fenn | not that many | 15:03 |
| kanzure | many get lost | 15:04 |
| kanzure | perhaps not 64 bit | 15:04 |
| fenn | how many connections in the brain? how many neurons? | 15:04 |
| kanzure | 100 trillion connections, 100 billion neurons, | 15:04 |
| kanzure | you'd need in vivo 'memory' so that you can persistent states | 15:04 |
| kanzure | but not only that, but you need /one/ ID per cell | 15:04 |
| kanzure | having *one* thing per cell is a generally nasty problem IIRC | 15:04 |
| fenn | so 47 bit for 100 trillion | 15:04 |
| kanzure | not each one is going to be necessarily used | 15:04 |
| kanzure | I mean, | 15:04 |
| kanzure | you need to have significantly more than you need | 15:05 |
| fenn | 23 quads (nucleotides) | 15:05 |
| kanzure | maintaining a persistent ID to a single cell is a very hard task | 15:05 |
| kanzure | apparently there are molecules that there are only 'one' copy of in a cell | 15:05 |
| fenn | not really, b-cells do it all the time | 15:06 |
| kanzure | something to do with whole genome replication | 15:06 |
| kanzure | how so? | 15:06 |
| fenn | dna shuffling and splicing | 15:06 |
| fenn | its how monoclonal antibodies work | 15:06 |
| kanzure | I'll have to look into that | 15:06 |
| kanzure | it would be awesome if we could start with an embryo and have each cell assigned to an 'address space' so that each child is assigned to a subset of that address space and so on | 15:07 |
| kanzure | that way the ID is encoded into the genome of each cell | 15:07 |
| kanzure | but that's not a solution for us | 15:07 |
| kanzure | (viral gene therapy could do it, I guess, but the assignment scheme might be more difficult in that case?) | 15:08 |
| fenn | what's wrong with random assignment? | 15:08 |
| kanzure | how do you know what's already used? | 15:08 |
| fenn | say you have a 64 bit id, and only need 47 bits, well there's a 1/2^(64-17) chance of an ID collision | 15:08 |
| fenn | s/17/47/ | 15:09 |
| fenn | around one in a million | 15:09 |
| kanzure | 1/(2^20) eh? with 100 trillion connections, 100 billion neurons, that's only 1E9, which is 2^30 right? | 15:10 |
| kanzure | hrm | 15:10 |
| fenn | is that right? i think there should be a factorial in there somewhere | 15:10 |
| kanzure | you have a million million | 15:10 |
| kanzure | so you'll have a million bad ones | 15:10 |
| fenn | ok, so play with the numbers until it works | 15:10 |
| fenn | summary of immunoglobulin DNA shuffling stuff: http://63.240.200.111/pages/pdfs/data/1998/154-19/15419-22.pdf | 15:13 |
| kanzure | so once you have your ID molecule in a cell, what then | 15:19 |
| kanzure | you still have to encode information somehow | 15:19 |
| kanzure | and the information that we want includes a lot of different variables | 15:19 |
| kanzure | stuff like neighboring connections, in vivo concentrations of various molecules, voltages, and so on | 15:20 |
| kanzure | if we can determine what information we want, and the ranges of the possible values of these variables (Markram is a good place to start looking), then we can do in vivo experimentation to get those values | 15:20 |
| fenn | honestly it sounds like a lot of work | 15:20 |
| kanzure | hrm, remember Markram's patch-clamp robot? we need to do that, except with the cells on their own | 15:21 |
| kanzure | yes, it sucks | 15:21 |
| fenn | and then you still have to reproduce it somehow | 15:21 |
| kanzure | well, if you want those exact details :/ | 15:21 |
| fenn | you could do some kind of transformation "mating" stuff like bacteria do | 15:21 |
| fenn | then splice the two ID's together | 15:21 |
| kanzure | for what? | 15:21 |
| fenn | so you'll get a chain of DNA containing all the neighbors' ID's | 15:21 |
| kanzure | oh, sure | 15:22 |
| kanzure | hrm | 15:22 |
| fenn | how is the 'connection strength' determined in a biological neuron? | 15:22 |
| kanzure | so there has to be a way to distinguish between 'IDs that we are looking to acquire/claim' versus modes where we're just trying to splice them together | 15:22 |
| kanzure | maybe we should move this discussion into ##neuroscience | 15:22 |
| fenn | re: cancer and nanoparticle delivery system, i wonder why nobody's made artifical/recombinant b-cells that target your specific type of cancer | 15:43 |
| kanzure | fenn: why did we need the immediate laser-induced stoppable polymerase system for in vitro DNA synthesis? | 16:32 |
| kanzure | actually, why did we need the laser | 16:32 |
| kanzure | not so much why did we need to stop it | 16:32 |
| kanzure | I know that we can't let it write multiple times, but why not just have it under running water | 16:32 |
| kanzure | a 'stream' or current of water of some sort | 16:32 |
| kanzure | so that upstream DNA molecules get it only once and downstream is protected the longest or something | 16:33 |
| kanzure | hrm, nevermind .downstream would suck. | 16:33 |
| kanzure | just do it biochemically and make it take forever | 16:37 |
| kanzure | 1 bp every 30 minutes, so it just sits there | 16:37 |
| kanzure | while you diffuse the signalers to tell it to dissociate and for another one to become active | 16:37 |
| kanzure | (those two messages can go out at the same time) | 16:37 |
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| ybit | """[13:52] <fenn> " soon, organ banks can actually start banking organs." wow someone's really blowing it """ :D | 17:08 |
| ybit | way away running some errands | 17:08 |
| ybit | feels good to be off work for a few days | 17:08 |
| kanzure | hurray for eureka moments | 17:13 |
| kanzure | you're not selecting for four different polymerases | 17:13 |
| kanzure | you're selecting for a strand that encodes the four different polymerases | 17:14 |
| kanzure | in fact, you're selecting for the in vitro DNA synthesis system that actually /works/ so it's kind of like starting off assuming that it can work in the end | 17:15 |
| kanzure | and then through building it up, the parts will be selected that actually work | 17:15 |
| fenn | kanzure: the laser is how you get the dna sequence into the cell | 17:41 |
| fenn | using another wavelength as the 'clock signal' just makes the system more reliable, higher data rate since you dont have to wait for some stupid gene product to get synthesized | 17:42 |
| fenn | 30 minutes per bp? gimme a break | 17:42 |
| fenn | the 30 minutes still has to be amazingly precise (unless you have a fluorescence indicator) | 17:43 |
| fenn | considering most bacteria _divide_ in less time than that, i think you'll have some problems | 17:44 |
| fenn | oh, i'm really going for in-vivo btw | 17:45 |
| kanzure | hrm | 17:46 |
| kanzure | well, selection experiment that we could do | 17:47 |
| kanzure | the selection, like I said, is of a normal polymerase | 17:47 |
| kanzure | take an ecoli genome | 17:47 |
| kanzure | insert a new polymerase into the genome, one that has a funky specificity for a binding sequence that does not appear in the ecoli genome | 17:47 |
| fenn | and then punish it severely unless it comes up with a DNA writozyme? | 17:47 |
| fenn | is that vegan? | 17:47 |
| kanzure | now insert that initiator sequence + four hack-polymerases next to each other | 17:48 |
| fenn | bacterial oppressor! | 17:48 |
| kanzure | these hack-polymerases are exactly the same, but they are hacked in the sense that (1) they allow a 'ghost template strand' (engineer the template-acceptor to be a copy of the ddNTP acceptor, except for some molecule that does /not/ appear in the system | 17:48 |
| kanzure | ) | 17:48 |
| kanzure | (2) that they are pausable (I have a pausing system with some molecular markers and so on, so it's good) | 17:48 |
| kanzure | now, signal the system to either make something to help it live or something to kill it | 17:49 |
| fenn | it all sounds a bit too magical | 17:49 |
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| kanzure | fenn_ what was the list message you received? | 17:54 |
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| fenn_ | grarg | 17:56 |
| fenn_ | 'sounds a bit too magical' was the last | 17:56 |
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| kanzure | uh oh | 17:56 |
| kanzure | that doesn't appear in this log | 17:57 |
| fenn | 'now signal the system to either..' | 17:57 |
| kanzure | bleh, I need to run | 17:58 |
| fenn | you'd think IRC would have a pingback for each message | 17:58 |
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| kanzure | Hi all. | 19:51 |
| kanzure | fenn_: http://heybryan.org/mediawiki/index.php/Polymerase#Another_way_of_saying_the_same_thing.2C_again | 19:55 |
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