1 00:00:05,269 --> 00:00:02,950 hi my name is amit kahana and i'm a 2 00:00:07,190 --> 00:00:05,279 student of professor doran lancet 3 00:00:08,390 --> 00:00:07,200 from the weizmann institute of science 4 00:00:10,150 --> 00:00:08,400 in israel 5 00:00:11,830 --> 00:00:10,160 and today i'd like to talk to you about 6 00:00:14,230 --> 00:00:11,840 compositional attractors 7 00:00:16,710 --> 00:00:14,240 and why we think they are so important 8 00:00:19,990 --> 00:00:16,720 for the study of the origin of life 9 00:00:22,550 --> 00:00:20,000 we in the lancet group approach 10 00:00:23,269 --> 00:00:22,560 the origin of life from a systems 11 00:00:26,710 --> 00:00:23,279 chemistry 12 00:00:29,750 --> 00:00:26,720 perspective and specifically we believe 13 00:00:31,509 --> 00:00:29,760 in the lipid first scenario 14 00:00:33,270 --> 00:00:31,519 a scenario that we have developed and 15 00:00:35,990 --> 00:00:33,280 promoted over the years 16 00:00:37,430 --> 00:00:36,000 and so i'd like to first start by 17 00:00:40,069 --> 00:00:37,440 describing it to you 18 00:00:40,549 --> 00:00:40,079 so you'll get the principles of how we 19 00:00:43,590 --> 00:00:40,559 think 20 00:00:46,069 --> 00:00:43,600 life has emerged so 21 00:00:47,190 --> 00:00:46,079 imagine a primordial setting in which we 22 00:00:49,430 --> 00:00:47,200 have lipids 23 00:00:50,470 --> 00:00:49,440 simple amphiphiles of many different 24 00:00:53,510 --> 00:00:50,480 types 25 00:00:55,430 --> 00:00:53,520 that can spontaneously self-assemble to 26 00:00:58,229 --> 00:00:55,440 generate micelles 27 00:01:00,790 --> 00:00:58,239 nanoscopic lipid assemblies of many many 28 00:01:03,110 --> 00:01:00,800 different compositions 29 00:01:04,229 --> 00:01:03,120 some assemblies would have unique 30 00:01:07,429 --> 00:01:04,239 compositions 31 00:01:09,990 --> 00:01:07,439 that could be preserved over time 32 00:01:10,950 --> 00:01:10,000 this is due to the mutually catalytic 33 00:01:13,990 --> 00:01:10,960 interactions 34 00:01:17,590 --> 00:01:14,000 between constituent lipids 35 00:01:23,030 --> 00:01:17,600 and the composition would be 36 00:01:26,149 --> 00:01:23,040 retained overgrowth and split events 37 00:01:28,230 --> 00:01:26,159 from which progeny is generated with 38 00:01:31,190 --> 00:01:28,240 some compositional mutations 39 00:01:33,109 --> 00:01:31,200 that underlie selection and further 40 00:01:34,870 --> 00:01:33,119 evolution 41 00:01:37,109 --> 00:01:34,880 now this cycle of compositional 42 00:01:39,429 --> 00:01:37,119 reproduction can be repeated 43 00:01:41,830 --> 00:01:39,439 again and again and down the road it 44 00:01:44,149 --> 00:01:41,840 will produce more elaborate protocells 45 00:01:45,190 --> 00:01:44,159 such as the consensual model of a 46 00:01:48,630 --> 00:01:45,200 protocell that we 47 00:01:51,830 --> 00:01:48,640 in the community adhere to 48 00:01:52,789 --> 00:01:51,840 and you can read more about uh the 49 00:01:55,030 --> 00:01:52,799 chemistry 50 00:01:56,149 --> 00:01:55,040 and the principles of our models and 51 00:01:58,950 --> 00:01:56,159 scenario 52 00:02:00,310 --> 00:01:58,960 in our papers specifically in our nature 53 00:02:04,230 --> 00:02:00,320 reviews chemistry 54 00:02:06,709 --> 00:02:04,240 that hopefully will be published soon 55 00:02:08,389 --> 00:02:06,719 and what is very interesting to us and 56 00:02:12,309 --> 00:02:08,399 specifically in this project 57 00:02:15,350 --> 00:02:12,319 is the notion of homeostatic growth 58 00:02:19,589 --> 00:02:15,360 what makes a 59 00:02:23,030 --> 00:02:19,599 an assembly retains its composition 60 00:02:25,990 --> 00:02:23,040 overgrowth and split events 61 00:02:26,470 --> 00:02:26,000 this is a crucial aspect of the lipid 62 00:02:30,070 --> 00:02:26,480 first 63 00:02:31,750 --> 00:02:30,080 scenario and this is exactly what we are 64 00:02:34,390 --> 00:02:31,760 researching in the lab 65 00:02:36,550 --> 00:02:34,400 using the guard model a rigorous 66 00:02:38,470 --> 00:02:36,560 chemistry kinetics formalism 67 00:02:40,309 --> 00:02:38,480 that's highly based on nature-like 68 00:02:43,030 --> 00:02:40,319 parameters 69 00:02:44,470 --> 00:02:43,040 what we do is simulate assemblies 70 00:02:47,830 --> 00:02:44,480 starting from 71 00:02:48,390 --> 00:02:47,840 random compositions and just let them 72 00:02:52,630 --> 00:02:48,400 run 73 00:02:55,990 --> 00:02:52,640 and see what emergent properties we find 74 00:02:59,030 --> 00:02:56,000 now curiously these assemblies 75 00:03:02,070 --> 00:02:59,040 reach a composome state 76 00:03:05,110 --> 00:03:02,080 in which they can self-reproduce 77 00:03:07,670 --> 00:03:05,120 very very fast which is 78 00:03:08,309 --> 00:03:07,680 quite strange because these compositions 79 00:03:11,589 --> 00:03:08,319 are very 80 00:03:13,030 --> 00:03:11,599 rare in compositional space and yet the 81 00:03:16,470 --> 00:03:13,040 simulations 82 00:03:18,470 --> 00:03:16,480 again and again reach them very fast 83 00:03:21,670 --> 00:03:18,480 and this has been bothering us for a 84 00:03:25,110 --> 00:03:21,680 while so we performed some new analysis 85 00:03:26,550 --> 00:03:25,120 and formally proved that these composome 86 00:03:29,190 --> 00:03:26,560 states 87 00:03:32,550 --> 00:03:29,200 are actually dynamic attractors in 88 00:03:35,190 --> 00:03:32,560 compositional space 89 00:03:36,390 --> 00:03:35,200 so what are dynamic attractors let's run 90 00:03:39,190 --> 00:03:36,400 through the definition 91 00:03:40,309 --> 00:03:39,200 an attractor is an area or section in 92 00:03:43,589 --> 00:03:40,319 our space 93 00:03:46,229 --> 00:03:43,599 in our example compositional space 94 00:03:48,869 --> 00:03:46,239 towards which a system tends to progress 95 00:03:51,910 --> 00:03:48,879 or evolve 96 00:03:52,949 --> 00:03:51,920 now it means that we can start in many 97 00:03:56,070 --> 00:03:52,959 different 98 00:03:58,550 --> 00:03:56,080 random initial conditions 99 00:04:00,149 --> 00:03:58,560 and no matter where we start from the 100 00:04:04,070 --> 00:04:00,159 system tends to progress 101 00:04:07,350 --> 00:04:04,080 and reach the basin of attraction 102 00:04:08,309 --> 00:04:07,360 and that once it is within the basin of 103 00:04:12,550 --> 00:04:08,319 attraction 104 00:04:16,629 --> 00:04:12,560 it is less susceptible to perturbations 105 00:04:21,749 --> 00:04:16,639 which means that it tends to not escape 106 00:04:29,670 --> 00:04:25,830 so we come to the question are composums 107 00:04:31,909 --> 00:04:29,680 dynamic attractors as it turns out 108 00:04:33,830 --> 00:04:31,919 they are and this is an analysis that 109 00:04:36,870 --> 00:04:33,840 can illustrate that 110 00:04:37,909 --> 00:04:36,880 this is a phase diagram a visualization 111 00:04:41,430 --> 00:04:37,919 that scientists 112 00:04:45,189 --> 00:04:41,440 use to portray attraction 113 00:04:46,870 --> 00:04:45,199 and it depicts one simulation run 114 00:04:48,390 --> 00:04:46,880 the different colors here are the 115 00:04:51,510 --> 00:04:48,400 different generations 116 00:04:52,950 --> 00:04:51,520 the micelle grow and divide and upon 117 00:04:55,430 --> 00:04:52,960 each division event 118 00:04:56,790 --> 00:04:55,440 a new generation begins so you can 119 00:04:59,270 --> 00:04:56,800 follow the 120 00:05:02,070 --> 00:04:59,280 entire trajectory of the micellar 121 00:05:08,629 --> 00:05:05,270 now the axes are similarity measures 122 00:05:10,790 --> 00:05:08,639 the y-axis is a measure of similarity 123 00:05:13,990 --> 00:05:10,800 between the current composition 124 00:05:17,029 --> 00:05:14,000 of the assembly and its flux which 125 00:05:19,830 --> 00:05:17,039 influences the the next 126 00:05:21,590 --> 00:05:19,840 move of the assembly in compositional 127 00:05:24,550 --> 00:05:21,600 space 128 00:05:25,590 --> 00:05:24,560 for us this is a temporal compositional 129 00:05:27,430 --> 00:05:25,600 stability 130 00:05:28,629 --> 00:05:27,440 measure because the higher the 131 00:05:30,469 --> 00:05:28,639 similarity the more 132 00:05:33,110 --> 00:05:30,479 the assembly tends to preserve its 133 00:05:35,830 --> 00:05:33,120 composition 134 00:05:36,790 --> 00:05:35,840 now the x-axis is a similarity measure 135 00:05:39,430 --> 00:05:36,800 between 136 00:05:40,870 --> 00:05:39,440 the current composition of the assembly 137 00:05:44,230 --> 00:05:40,880 and the combo type 138 00:05:45,110 --> 00:05:44,240 the exact composition at which uh the 139 00:05:47,590 --> 00:05:45,120 assembly 140 00:05:49,270 --> 00:05:47,600 attains self-reproduction capacity and 141 00:05:52,469 --> 00:05:49,280 this is why we treat it 142 00:05:55,590 --> 00:05:52,479 as a reproduction capacity measure 143 00:05:58,390 --> 00:05:55,600 so you can see how the assembly starts 144 00:06:01,909 --> 00:05:58,400 at a random place 145 00:06:04,230 --> 00:06:01,919 goes to a 146 00:06:06,070 --> 00:06:04,240 place where it attains a high temporal 147 00:06:08,390 --> 00:06:06,080 compositional stability 148 00:06:10,150 --> 00:06:08,400 for a few generations before it escapes 149 00:06:13,350 --> 00:06:10,160 from that small haven 150 00:06:15,749 --> 00:06:13,360 and then rapidly 151 00:06:19,350 --> 00:06:15,759 merge with the compo type at the top 152 00:06:22,870 --> 00:06:19,360 right corner of the phase diagram 153 00:06:24,150 --> 00:06:22,880 now interestingly this pattern is highly 154 00:06:27,510 --> 00:06:24,160 reproducible 155 00:06:30,870 --> 00:06:27,520 you can see it in many many runs of our 156 00:06:34,629 --> 00:06:30,880 guard simulations 157 00:06:36,390 --> 00:06:34,639 so here for example we have 20 such runs 158 00:06:38,629 --> 00:06:36,400 and again you can see how they start in 159 00:06:39,350 --> 00:06:38,639 different random places in compositional 160 00:06:42,790 --> 00:06:39,360 space 161 00:06:46,550 --> 00:06:42,800 compositions 162 00:06:49,749 --> 00:06:46,560 um stay for a bit at different places 163 00:06:52,309 --> 00:06:49,759 but then quickly coalesce 164 00:06:53,189 --> 00:06:52,319 towards the top right corner where the 165 00:06:57,110 --> 00:06:53,199 combo type 166 00:06:58,790 --> 00:06:57,120 lies in a team's composable state 167 00:07:00,390 --> 00:06:58,800 and this is a major dynamic attractor 168 00:07:04,950 --> 00:07:00,400 you can see how all 169 00:07:07,430 --> 00:07:04,960 the runs just rapidly 170 00:07:08,629 --> 00:07:07,440 go towards that corner and even when 171 00:07:10,550 --> 00:07:08,639 they reach there 172 00:07:11,830 --> 00:07:10,560 there's still fluctuations there's still 173 00:07:15,510 --> 00:07:11,840 a place for high 174 00:07:17,909 --> 00:07:15,520 variation in the composition but 175 00:07:19,430 --> 00:07:17,919 the compositions are still within the 176 00:07:21,270 --> 00:07:19,440 basin of attraction 177 00:07:22,950 --> 00:07:21,280 so no matter how much they fluctuate 178 00:07:29,029 --> 00:07:22,960 they still 179 00:07:35,430 --> 00:07:32,150 so you may ask why do we care 180 00:07:38,309 --> 00:07:35,440 about the tractors and the answer is 181 00:07:41,589 --> 00:07:38,319 that attractors have many advantages 182 00:07:44,550 --> 00:07:41,599 specifically for the origin of life 183 00:07:45,909 --> 00:07:44,560 first and foremost dynamic detractors 184 00:07:49,189 --> 00:07:45,919 allow 185 00:07:52,230 --> 00:07:49,199 assemblies of different 186 00:07:52,869 --> 00:07:52,240 random initial compositions to fastly 187 00:07:55,990 --> 00:07:52,879 reach 188 00:07:59,430 --> 00:07:56,000 a surf reproduction state 189 00:08:02,950 --> 00:07:59,440 in other words self-reproduction 190 00:08:06,629 --> 00:08:02,960 is attractive to chemical systems 191 00:08:09,830 --> 00:08:06,639 this is important because it means that 192 00:08:10,950 --> 00:08:09,840 the emergence of lives becomes much more 193 00:08:17,270 --> 00:08:10,960 probable 194 00:08:21,749 --> 00:08:19,830 attractors also assist the assemblies to 195 00:08:23,110 --> 00:08:21,759 reach self-reproduction in the face of 196 00:08:26,150 --> 00:08:23,120 the many challenges 197 00:08:28,469 --> 00:08:26,160 that come with a probiotic setting 198 00:08:29,909 --> 00:08:28,479 among them the high environmental 199 00:08:32,949 --> 00:08:29,919 molecular diversity 200 00:08:36,469 --> 00:08:32,959 of the different lipids that surrounding 201 00:08:38,870 --> 00:08:36,479 the assemblies the uneven 202 00:08:41,190 --> 00:08:38,880 or fluctuating concentrations of these 203 00:08:44,389 --> 00:08:41,200 lipids 204 00:08:47,110 --> 00:08:44,399 and the varied levels of catalysis high 205 00:08:49,110 --> 00:08:47,120 catalysis locators and anything in 206 00:08:51,030 --> 00:08:49,120 between 207 00:08:54,949 --> 00:08:51,040 these are parameters that we are 208 00:08:58,150 --> 00:08:54,959 exploring in our project currently 209 00:09:00,389 --> 00:08:58,160 and a more theoretical thought we see 210 00:09:03,910 --> 00:09:00,399 systems in which there are 211 00:09:05,509 --> 00:09:03,920 many combo types not only one 212 00:09:07,269 --> 00:09:05,519 and that we see transitions between 213 00:09:09,750 --> 00:09:07,279 compotypes 214 00:09:10,790 --> 00:09:09,760 and these transitions are governed by 215 00:09:14,070 --> 00:09:10,800 the attraction 216 00:09:16,949 --> 00:09:14,080 of each of the compotype state 217 00:09:17,910 --> 00:09:16,959 and so we can describe the evolutionary 218 00:09:19,750 --> 00:09:17,920 routes 219 00:09:21,670 --> 00:09:19,760 the transition between the combo types 220 00:09:21,990 --> 00:09:21,680 based on their attraction which i think 221 00:09:27,509 --> 00:09:22,000 is 222 00:09:29,590 --> 00:09:27,519 conclusions and take-home messages 223 00:09:31,590 --> 00:09:29,600 about the project and about why i think 224 00:09:34,230 --> 00:09:31,600 attractors are cool and are important 225 00:09:37,110 --> 00:09:34,240 for the study of the origin of life 226 00:09:37,990 --> 00:09:37,120 so first we discovered that mixed 227 00:09:39,750 --> 00:09:38,000 micelles 228 00:09:41,590 --> 00:09:39,760 can self-reproduce and that their 229 00:09:45,430 --> 00:09:41,600 self-reproduction state 230 00:09:47,269 --> 00:09:45,440 is a dynamic attractor this means and i 231 00:09:49,990 --> 00:09:47,279 will iterate this point 232 00:09:52,230 --> 00:09:50,000 that self-reproduction is attractive to 233 00:09:54,630 --> 00:09:52,240 chemical systems 234 00:09:56,630 --> 00:09:54,640 we further explored and found that the 235 00:09:58,470 --> 00:09:56,640 attraction stems from the inherent 236 00:10:00,550 --> 00:09:58,480 mutually catalytic interactions 237 00:10:02,550 --> 00:10:00,560 between the constituent lipids of the 238 00:10:05,750 --> 00:10:02,560 assemblies the different 239 00:10:08,310 --> 00:10:05,760 simple molecules in the system and that 240 00:10:10,230 --> 00:10:08,320 the attraction towards self-reproduction 241 00:10:11,910 --> 00:10:10,240 actually helps to mitigate the 242 00:10:13,990 --> 00:10:11,920 challenges of existing 243 00:10:16,829 --> 00:10:14,000 in a probiotic setting as i have 244 00:10:20,949 --> 00:10:19,030 additionally for assemblies that exist 245 00:10:22,790 --> 00:10:20,959 within the basin of attraction 246 00:10:24,949 --> 00:10:22,800 there's still room for compositional 247 00:10:26,710 --> 00:10:24,959 variation and optimization as we've seen 248 00:10:29,670 --> 00:10:26,720 in the phase diagrams 249 00:10:31,990 --> 00:10:29,680 and this is necessary for selection and 250 00:10:33,670 --> 00:10:32,000 further evolution towards life as we 251 00:10:36,550 --> 00:10:33,680 know it 252 00:10:37,750 --> 00:10:36,560 and perhaps the most important point 253 00:10:40,630 --> 00:10:37,760 attractors 254 00:10:41,910 --> 00:10:40,640 as a notion could help us explore 255 00:10:44,949 --> 00:10:41,920 chemical space 256 00:10:46,630 --> 00:10:44,959 to find the roots of the origin of life 257 00:10:49,590 --> 00:10:46,640 we don't need to look for specific 258 00:10:51,350 --> 00:10:49,600 molecules or even specific compositions 259 00:10:53,910 --> 00:10:51,360 we need to generate different 260 00:10:57,750 --> 00:10:53,920 compositions in different environments 261 00:11:00,949 --> 00:10:57,760 and see toward what states the systems 262 00:11:02,790 --> 00:11:00,959 tend to evolve and this would really 263 00:11:04,949 --> 00:11:02,800 help us define the attractors 264 00:11:06,550 --> 00:11:04,959 and define the states in which systems 265 00:11:08,470 --> 00:11:06,560 can self-reproduce 266 00:11:10,389 --> 00:11:08,480 and this is why i think attractors are 267 00:11:11,430 --> 00:11:10,399 so so important not only to understand 268 00:11:16,069 --> 00:11:11,440 the origin of life 269 00:11:18,230 --> 00:11:16,079 but also to search and explore it 270 00:11:19,750 --> 00:11:18,240 i quickly want to thank my mentor 271 00:11:21,990 --> 00:11:19,760 professor dawn lansette our 272 00:11:24,069 --> 00:11:22,000 collaborators in this project 273 00:11:25,030 --> 00:11:24,079 here is my email you can contact me with 274 00:11:27,590 --> 00:11:25,040 any question 275 00:11:28,790 --> 00:11:27,600 or comment or just speak to me during 276 00:11:31,269 --> 00:11:28,800 this conference 277 00:11:32,870 --> 00:11:31,279 and read our papers engage with our 278 00:11:35,350 --> 00:11:32,880 science