1 00:00:11,440 --> 00:00:10,299 assemble at the monomer level so we went 2 00:00:13,090 --> 00:00:11,450 back we looked at the different 3 00:00:14,410 --> 00:00:13,100 different building blocks these 4 00:00:17,350 --> 00:00:14,420 molecular recognition units the 5 00:00:19,660 --> 00:00:17,360 appearance of primitives and out of 27 6 00:00:21,160 --> 00:00:19,670 molecules that are purines that have 7 00:00:23,019 --> 00:00:21,170 substitution for the two six or eight 8 00:00:24,700 --> 00:00:23,029 position only one comes out and that's 9 00:00:26,139 --> 00:00:24,710 the one we just heard about wanna see an 10 00:00:27,970 --> 00:00:26,149 able to form self structures in the 11 00:00:30,639 --> 00:00:27,980 presence of ions actually that need to 12 00:00:32,830 --> 00:00:30,649 be coordinating these structures and if 13 00:00:36,010 --> 00:00:32,840 we look at all the possibilities for the 14 00:00:38,290 --> 00:00:36,020 perimeters what we have is 54 related 15 00:00:40,509 --> 00:00:38,300 molecules where we substitute at the 2 4 16 00:00:42,160 --> 00:00:40,519 5 6 positions and those are you see that 17 00:00:44,169 --> 00:00:42,170 I'm curing all Kuehl permitting molecule 18 00:00:46,419 --> 00:00:44,179 over there let's do those of the means 19 00:00:48,939 --> 00:00:46,429 carbonyl groups are hydrogen we now have 20 00:00:50,590 --> 00:00:48,949 pity for related molecules and then if 21 00:00:52,989 --> 00:00:50,600 we also include another molecule that 22 00:00:55,869 --> 00:00:52,999 comes out of many prebiotic model 23 00:00:58,389 --> 00:00:55,879 reactions and has been found on on 24 00:01:01,090 --> 00:00:58,399 molecule molecules in space coming down 25 00:01:03,610 --> 00:01:01,100 from meteorites we see that there is 26 00:01:06,340 --> 00:01:03,620 about 10 more possibilities for these 27 00:01:08,080 --> 00:01:06,350 molecules that might have been present 28 00:01:10,359 --> 00:01:08,090 in a periodic inventory that could 29 00:01:12,730 --> 00:01:10,369 potentially assemble however of these 30 00:01:15,130 --> 00:01:12,740 molecules only four of them have been 31 00:01:17,050 --> 00:01:15,140 found to assemble in organic solutions 32 00:01:18,880 --> 00:01:17,060 so this is actually sort of carrying 33 00:01:21,639 --> 00:01:18,890 over from the field of super molecular 34 00:01:23,020 --> 00:01:21,649 assembly so we wanted to see if these 35 00:01:24,219 --> 00:01:23,030 molecules which are potentially 36 00:01:27,190 --> 00:01:24,229 prebiotic and three of these haven't 37 00:01:28,330 --> 00:01:27,200 found in model reactions could present 38 00:01:33,969 --> 00:01:28,340 Lisa semble into something that's 39 00:01:36,700 --> 00:01:33,979 similar to a duplex or a a polymer that 40 00:01:39,310 --> 00:01:36,710 is able to store information so choosing 41 00:01:42,130 --> 00:01:39,320 two of these try me in a primitive which 42 00:01:43,810 --> 00:01:42,140 is here and blue and cyanuric acid you 43 00:01:46,630 --> 00:01:43,820 can see that they assemble actually in 44 00:01:49,359 --> 00:01:46,640 this rosette hex at formation and what 45 00:01:51,039 --> 00:01:49,369 it should be immediately evident is that 46 00:01:51,940 --> 00:01:51,049 you see that these hydrogen bonding 47 00:01:53,469 --> 00:01:51,950 interaction these are very specific 48 00:01:54,789 --> 00:01:53,479 hydrogen bond interactions you have two 49 00:01:56,709 --> 00:01:54,799 faces instead of just the one phase 50 00:02:00,130 --> 00:01:56,719 which allows you to go into this larger 51 00:02:02,849 --> 00:02:00,140 structure and so just like watson-crick 52 00:02:04,539 --> 00:02:02,859 base pairing you have the two main 53 00:02:05,289 --> 00:02:04,549 energetic terms that are bringing these 54 00:02:07,510 --> 00:02:05,299 things together through molecular 55 00:02:10,240 --> 00:02:07,520 recognition is the hydrogen bonding and 56 00:02:12,100 --> 00:02:10,250 also the PI pi stacking to form this 57 00:02:13,600 --> 00:02:12,110 larger structure so we were asking is 58 00:02:15,850 --> 00:02:13,610 this the ancestry of watching creek base 59 00:02:17,970 --> 00:02:15,860 pair another another reason we really 60 00:02:20,980 --> 00:02:17,980 like this is because of theoretical 61 00:02:22,810 --> 00:02:20,990 investigations into sort of what is the 62 00:02:24,750 --> 00:02:22,820 minimum size you need to drive that you 63 00:02:27,100 --> 00:02:24,760 have the hydrophobic effect drive 64 00:02:29,680 --> 00:02:27,110 assemblies and this is worth it was done 65 00:02:32,440 --> 00:02:29,690 by a David Chandler and they're in the 66 00:02:34,450 --> 00:02:32,450 about that's seven eight years ago he is 67 00:02:36,370 --> 00:02:34,460 other groups of recently experimentally 68 00:02:38,650 --> 00:02:36,380 shown that you need to get up over this 69 00:02:39,700 --> 00:02:38,660 size of about one nanometer and once 70 00:02:42,430 --> 00:02:39,710 you're over that size about one 71 00:02:44,620 --> 00:02:42,440 nanometer water you can really get the 72 00:02:48,430 --> 00:02:44,630 hydrophobic effect to kick in and to 73 00:02:51,760 --> 00:02:48,440 allow for the assembly of through the 74 00:02:53,140 --> 00:02:51,770 hydrophobic effect and the heck's that 75 00:02:54,790 --> 00:02:53,150 has this you can see it's got a much 76 00:02:56,110 --> 00:02:54,800 larger surface area than it duplex but 77 00:02:58,690 --> 00:02:56,120 the duplex does not have this isn't 78 00:02:59,949 --> 00:02:58,700 cross this minimum threshold and from 79 00:03:01,750 --> 00:02:59,959 these calculations you have about thirty 80 00:03:03,850 --> 00:03:01,760 kcals per mole and that's actually a lot 81 00:03:05,530 --> 00:03:03,860 of energy for exposing that surface so 82 00:03:08,350 --> 00:03:05,540 that's why you want to bury these these 83 00:03:11,500 --> 00:03:08,360 surfaces forming very long polymers and 84 00:03:13,530 --> 00:03:11,510 I'll get to that a second so you know 85 00:03:16,660 --> 00:03:13,540 keeping this in mind we went after a 86 00:03:18,460 --> 00:03:16,670 very simple system to first brew the 87 00:03:19,810 --> 00:03:18,470 concept that the the alternative basis 88 00:03:22,240 --> 00:03:19,820 might be able to allow for the formation 89 00:03:24,370 --> 00:03:22,250 of polymers and so what we did is we 90 00:03:26,770 --> 00:03:24,380 took triming a primitive added a 91 00:03:29,020 --> 00:03:26,780 aliphatic acid tail to it sort of blocks 92 00:03:32,620 --> 00:03:29,030 of face and what you were calling tap is 93 00:03:34,120 --> 00:03:32,630 hear the name came from my boss it was a 94 00:03:37,270 --> 00:03:34,130 way for like eight months in Barcelona 95 00:03:38,860 --> 00:03:37,280 so during that time we Calot thats not 96 00:03:41,530 --> 00:03:38,870 the actual correct I you pack name but 97 00:03:44,710 --> 00:03:41,540 it we kept to it and we kept going with 98 00:03:47,170 --> 00:03:44,720 it so each o cyanuric acid in you go 99 00:03:48,850 --> 00:03:47,180 into a rosette this hex I'd then stacks 100 00:03:49,840 --> 00:03:48,860 on top of each other and what's cool 101 00:03:51,610 --> 00:03:49,850 about this is you just throw them in 102 00:03:52,930 --> 00:03:51,620 right away any form a gel that's the 103 00:03:55,210 --> 00:03:52,940 first thing we saw we threw these both 104 00:03:57,970 --> 00:03:55,220 molecules in and spontaneously a gel 105 00:04:00,009 --> 00:03:57,980 forms this is indicative of long 106 00:04:01,570 --> 00:04:00,019 polymers that are cross-linked we want 107 00:04:04,240 --> 00:04:01,580 to get more information about these 108 00:04:07,030 --> 00:04:04,250 polymers which are cross-linked so we 109 00:04:09,190 --> 00:04:07,040 looked at we use microscopy and here we 110 00:04:11,289 --> 00:04:09,200 have an AFM and a TEM and the AFM is 111 00:04:12,490 --> 00:04:11,299 atomic force microscopy and if you see 112 00:04:14,830 --> 00:04:12,500 the blue and the red or the cross 113 00:04:16,630 --> 00:04:14,840 sections and you can get a height and 114 00:04:18,699 --> 00:04:16,640 the heights going to be pretty good for 115 00:04:20,259 --> 00:04:18,709 telling you how large it is in each of 116 00:04:21,699 --> 00:04:20,269 these come to about two nanometers and 117 00:04:23,560 --> 00:04:21,709 that's the actual predicted size of one 118 00:04:25,870 --> 00:04:23,570 of these rosettes so we see that we are 119 00:04:27,370 --> 00:04:25,880 forming stacked rosettes we also have 120 00:04:30,670 --> 00:04:27,380 some other spectroscopic evidence of 121 00:04:31,660 --> 00:04:30,680 that but these pre are prettier so you 122 00:04:34,390 --> 00:04:31,670 see that we're forming 123 00:04:36,580 --> 00:04:34,400 a long polymers as well and we also see 124 00:04:38,230 --> 00:04:36,590 this in the TM transmission electron 125 00:04:40,780 --> 00:04:38,240 microscope and these are actually 126 00:04:43,210 --> 00:04:40,790 laterally assembled and again you have 127 00:04:46,120 --> 00:04:43,220 the two ain't the two nanometers as the 128 00:04:47,620 --> 00:04:46,130 size of the width so what's really just 129 00:04:49,060 --> 00:04:47,630 about these is how long they are again 130 00:04:51,160 --> 00:04:49,070 it's because of that hydrophobic effect 131 00:04:52,780 --> 00:04:51,170 you don't want to expose these surfaces 132 00:04:54,310 --> 00:04:52,790 so you form very long polymers but this 133 00:04:57,340 --> 00:04:54,320 polymer here which is a little bit over 134 00:04:59,770 --> 00:04:57,350 a micron contains about 20,000 highly 135 00:05:03,210 --> 00:04:59,780 ordered nucleobases that are positioned 136 00:05:05,740 --> 00:05:03,220 right next to each other in solution so 137 00:05:07,210 --> 00:05:05,750 what we see from self assemblies we see 138 00:05:10,570 --> 00:05:07,220 that it overcomes from these problems 139 00:05:11,680 --> 00:05:10,580 such as base selection in a very complex 140 00:05:12,820 --> 00:05:11,690 mixture and we've actually thrown an 141 00:05:14,230 --> 00:05:12,830 other nucleobase and we see that it 142 00:05:16,140 --> 00:05:14,240 preferentially only these are 143 00:05:18,640 --> 00:05:16,150 incorporated into these assemblies 144 00:05:21,460 --> 00:05:18,650 connectivity you're now pre organizing 145 00:05:23,140 --> 00:05:21,470 for corrects coupling we are forming 146 00:05:24,460 --> 00:05:23,150 very long polymers but of course the 147 00:05:26,410 --> 00:05:24,470 next step is to link them together these 148 00:05:29,290 --> 00:05:26,420 are all non covalent assemblies while 149 00:05:31,170 --> 00:05:29,300 they will enhance the ability to form 150 00:05:33,100 --> 00:05:31,180 ligation between them because the 151 00:05:34,480 --> 00:05:33,110 concentration local concentration is so 152 00:05:37,600 --> 00:05:34,490 high when you put them next to each 153 00:05:39,460 --> 00:05:37,610 other they are different we also have 154 00:05:42,040 --> 00:05:39,470 glycosidic bond formation that is 155 00:05:43,810 --> 00:05:42,050 actually pretty pretty good in high 156 00:05:45,250 --> 00:05:43,820 yields with these with some of these 157 00:05:50,020 --> 00:05:45,260 assembly molecules and we just submitted 158 00:05:52,230 --> 00:05:50,030 this work so it should be AB soon but if 159 00:05:54,640 --> 00:05:52,240 we were to accept that these nucleobases 160 00:05:56,680 --> 00:05:54,650 predated the nucleobases in life today 161 00:06:00,160 --> 00:05:56,690 we must also accept that then there was 162 00:06:04,510 --> 00:06:00,170 an evolution from a a proto system a 163 00:06:06,160 --> 00:06:04,520 proto RNA or a prerna into the into the 164 00:06:08,020 --> 00:06:06,170 structure that we have today and i'm 165 00:06:10,150 --> 00:06:08,030 going to use the the ship of theseus 166 00:06:13,390 --> 00:06:10,160 this is a paradox put up I plutarch to 167 00:06:15,820 --> 00:06:13,400 sort of give an idea of our ideas on how 168 00:06:17,470 --> 00:06:15,830 this transfer turn doesn't happens he 169 00:06:19,630 --> 00:06:17,480 postulated that if you take a ship and 170 00:06:21,340 --> 00:06:19,640 you deconstruct it and then change all 171 00:06:23,740 --> 00:06:21,350 its parts and then put it back together 172 00:06:25,240 --> 00:06:23,750 is it still the same ship and I mean we 173 00:06:26,380 --> 00:06:25,250 could argue one way or the other but I 174 00:06:28,630 --> 00:06:26,390 think we'd all argue that it has still 175 00:06:30,550 --> 00:06:28,640 at the same function the ship is still 176 00:06:33,160 --> 00:06:30,560 going to be able to maneuver the Seas in 177 00:06:34,960 --> 00:06:33,170 the work the same way how about if you 178 00:06:36,670 --> 00:06:34,970 actually change just one part of the 179 00:06:38,080 --> 00:06:36,680 ship at a time sort of that ship is sort 180 00:06:40,090 --> 00:06:38,090 of involved in order to fit a certain 181 00:06:41,890 --> 00:06:40,100 scenario certain need then you might 182 00:06:43,510 --> 00:06:41,900 have several ships that are going to 183 00:06:44,770 --> 00:06:43,520 come in at different times to facilitate 184 00:06:46,840 --> 00:06:44,780 a different need where 185 00:06:48,160 --> 00:06:46,850 you would have a canoe maybe to start 186 00:06:49,660 --> 00:06:48,170 with you want it to just navigate a 187 00:06:51,970 --> 00:06:49,670 creek but you couldn't do that with this 188 00:06:53,500 --> 00:06:51,980 very large ship here however you still 189 00:06:55,720 --> 00:06:53,510 are conserving some basic principles 190 00:06:57,640 --> 00:06:55,730 such as a whole or a sale depending on 191 00:06:59,710 --> 00:06:57,650 what is it required and we see that 192 00:07:01,840 --> 00:06:59,720 already from just the the change if we 193 00:07:05,379 --> 00:07:01,850 were to accept the RNA world the change 194 00:07:07,240 --> 00:07:05,389 going from RNA to DNA where you actually 195 00:07:09,340 --> 00:07:07,250 have a change to the architecture in the 196 00:07:10,690 --> 00:07:09,350 the two position here you don't have 197 00:07:12,129 --> 00:07:10,700 this hydroxyl which is good because that 198 00:07:13,240 --> 00:07:12,139 light leads the strand cleavage and 199 00:07:17,560 --> 00:07:13,250 that's why people keep talking about how 200 00:07:18,820 --> 00:07:17,570 RNA so so pesky to have around so you 201 00:07:20,920 --> 00:07:18,830 you have actually changes in the 202 00:07:22,840 --> 00:07:20,930 physical architecture that went to a DNA 203 00:07:25,060 --> 00:07:22,850 which is a lot better for storing large 204 00:07:26,980 --> 00:07:25,070 genetic information like we have in life 205 00:07:29,500 --> 00:07:26,990 today there's also some changes to the 206 00:07:32,770 --> 00:07:29,510 nucleobases these are changes that are 207 00:07:35,710 --> 00:07:32,780 all although small impact the situation 208 00:07:38,530 --> 00:07:35,720 greatly so what could have predated 209 00:07:41,950 --> 00:07:38,540 these systems could be a polymer that is 210 00:07:44,500 --> 00:07:41,960 more amiable to self-assembly to being 211 00:07:47,500 --> 00:07:44,510 able to be spontaneously generated under 212 00:07:50,500 --> 00:07:47,510 geophysical conditions and there might 213 00:07:52,930 --> 00:07:50,510 have been more that that preceded these 214 00:07:54,730 --> 00:07:52,940 these structures and this this could be 215 00:07:56,469 --> 00:07:54,740 thought of as or Dale puts as a gloomy 216 00:08:00,430 --> 00:07:56,479 prospects if there are all these 217 00:08:02,350 --> 00:08:00,440 different scenarios what which one is 218 00:08:03,969 --> 00:08:02,360 right and is it really even good idea to 219 00:08:05,380 --> 00:08:03,979 go after them but you can start 220 00:08:06,370 --> 00:08:05,390 constraining things and many people have 221 00:08:08,200 --> 00:08:06,380 already started building different 222 00:08:09,460 --> 00:08:08,210 architectures changing out the base is 223 00:08:11,230 --> 00:08:09,470 changing out the backbone and change it 224 00:08:16,180 --> 00:08:11,240 at the phosphate and found that we can 225 00:08:17,710 --> 00:08:16,190 form structures that are just as good in 226 00:08:19,750 --> 00:08:17,720 certain scenarios such as just as good 227 00:08:21,580 --> 00:08:19,760 as assembling story information they can 228 00:08:22,570 --> 00:08:21,590 actually be catalysts to you going to 229 00:08:24,969 --> 00:08:22,580 form you can change the background 230 00:08:27,940 --> 00:08:24,979 remove the ribose and you can still have 231 00:08:29,590 --> 00:08:27,950 a catalyst that is that is the 232 00:08:33,969 --> 00:08:29,600 spontaneously emerges from a pool of 233 00:08:36,520 --> 00:08:33,979 other sequences so I just want to put 234 00:08:37,630 --> 00:08:36,530 this out there this really is something 235 00:08:38,770 --> 00:08:37,640 that we were talking about earlier could 236 00:08:44,350 --> 00:08:38,780 life also have taken a different path 237 00:08:46,750 --> 00:08:44,360 and again if it did it if it's not we're 238 00:08:49,030 --> 00:08:46,760 not at that the DNA or RNA and we don't 239 00:08:53,250 --> 00:08:49,040 see that in biology or see that in a 240 00:08:56,980 --> 00:08:53,260 biology paper we find it outside well 241 00:08:58,300 --> 00:08:56,990 it's not such a dire position like what 242 00:08:59,769 --> 00:08:58,310 what you 243 00:09:01,870 --> 00:08:59,779 really need to look for when we start 244 00:09:03,700 --> 00:09:01,880 looking for genetic systems that are not 245 00:09:04,840 --> 00:09:03,710 like our own and we can constrain that 246 00:09:07,930 --> 00:09:04,850 by understanding the physicochemical 247 00:09:11,110 --> 00:09:07,940 properties of these molecules that are 248 00:09:15,480 --> 00:09:11,120 able to sustain information storage or 249 00:09:17,710 --> 00:09:15,490 catalysis and with that acknowledgments 250 00:09:22,329 --> 00:09:17,720 Nick HUD Michael Shannon was an 251 00:09:24,340 --> 00:09:22,339 undergrad I worked with Diego NASA NSF 252 00:09:26,560 --> 00:09:24,350 the Center for chemical pollution which 253 00:09:32,950 --> 00:09:26,570 is based in Atlanta and if you have any 254 00:09:36,850 --> 00:09:32,960 questions have any time take them think 255 00:09:38,829 --> 00:09:36,860 we have time for learning to have you 256 00:09:41,140 --> 00:09:38,839 tried looking at the Assembly of these 257 00:09:44,579 --> 00:09:41,150 polymers under different conditions like 258 00:09:47,500 --> 00:09:44,589 different temperature over here yeah 259 00:09:49,570 --> 00:09:47,510 different temperature different ph I 260 00:09:51,640 --> 00:09:49,580 other things it's interesting to these 261 00:09:54,130 --> 00:09:51,650 polymers on there if there's some 262 00:09:56,019 --> 00:09:54,140 arguments about PKA also pH if your 263 00:09:59,230 --> 00:09:56,029 these all assemble at ph 7 really well 264 00:10:01,390 --> 00:09:59,240 moving away from the ph you have them 265 00:10:03,010 --> 00:10:01,400 start to fall apart which could be also 266 00:10:05,020 --> 00:10:03,020 you could you think of it was a way to 267 00:10:06,640 --> 00:10:05,030 maybe get around strand ambition or 268 00:10:09,490 --> 00:10:06,650 something work yet you guess which is 269 00:10:12,430 --> 00:10:09,500 temperature wise they are they do 270 00:10:14,410 --> 00:10:12,440 assemble through just they're not 271 00:10:16,510 --> 00:10:14,420 they're empathically a prone to assemble 272 00:10:18,130 --> 00:10:16,520 that are not entropically driven so at 273 00:10:19,810 --> 00:10:18,140 least for the initial assembly to form 274 00:10:26,440 --> 00:10:19,820 the rosette which means that coin it 275 00:10:29,530 --> 00:10:26,450 down you can get more assembled okay hi 276 00:10:31,390 --> 00:10:29,540 okay so my question and actually this 277 00:10:32,920 --> 00:10:31,400 was I read the paper but it's still 278 00:10:35,140 --> 00:10:32,930 unclear to me I'm so you've got the tip 279 00:10:36,340 --> 00:10:35,150 you've got your rosettes and so the blue 280 00:10:37,510 --> 00:10:36,350 is always on top of the red is always on 281 00:10:39,970 --> 00:10:37,520 top of the blue is always on top of the 282 00:10:43,540 --> 00:10:39,980 red how do you propose that a system 283 00:10:45,220 --> 00:10:43,550 like that becomes a system like RNA 284 00:10:46,720 --> 00:10:45,230 where the order of the basis is 285 00:10:50,890 --> 00:10:46,730 different and drives evolution like how 286 00:10:52,720 --> 00:10:50,900 does this how do you make these polymers 287 00:10:54,430 --> 00:10:52,730 that are all essentially the same evolve 288 00:10:55,870 --> 00:10:54,440 into something that's not the same yeah 289 00:10:58,030 --> 00:10:55,880 I mean that was actually just a drawing 290 00:11:00,220 --> 00:10:58,040 though so that was a problem that's what 291 00:11:02,320 --> 00:11:00,230 we chose and you know I've we've had to 292 00:11:03,970 --> 00:11:02,330 come up again like people assume that 293 00:11:05,470 --> 00:11:03,980 you have these that they're going to be 294 00:11:08,440 --> 00:11:05,480 stacked on top of each other a certain 295 00:11:09,579 --> 00:11:08,450 way this is a very greasy surface we 296 00:11:12,100 --> 00:11:09,589 don't actually have this atomic 297 00:11:13,990 --> 00:11:12,110 resolution but you 298 00:11:15,400 --> 00:11:14,000 expect and what we've done by throwing 299 00:11:17,019 --> 00:11:15,410 in chiral molecules they had a key 300 00:11:20,259 --> 00:11:17,029 little twist so they're off a little bit 301 00:11:21,819 --> 00:11:20,269 and we don't know exactly either stacked 302 00:11:24,699 --> 00:11:21,829 and that was a problem of my advisor 303 00:11:26,650 --> 00:11:24,709 using his software and not spacing them 304 00:11:30,940 --> 00:11:26,660 out in a way that's you know maybe or