1 00:00:17,683 --> 00:00:18,600 BARBARA IMPERIALI: OK. 2 00:00:18,600 --> 00:00:19,642 We're going to get going. 3 00:00:19,642 --> 00:00:21,740 Now, we have a small class this year 4 00:00:21,740 --> 00:00:24,830 because of changes in the institute with pass/fail types 5 00:00:24,830 --> 00:00:29,360 of things, but Professor Martin and Dr. Ray 6 00:00:29,360 --> 00:00:33,020 and I consider this to be a special opportunity for us 7 00:00:33,020 --> 00:00:36,320 to run the course a little bit differently with a few more 8 00:00:36,320 --> 00:00:38,150 quirks and surprises. 9 00:00:38,150 --> 00:00:40,460 Because we have a small number of you, 10 00:00:40,460 --> 00:00:42,290 we can listen to you all. 11 00:00:42,290 --> 00:00:44,180 We can get input from you. 12 00:00:44,180 --> 00:00:46,490 We can even get feedback from you of something 13 00:00:46,490 --> 00:00:48,650 you might like to see more of. 14 00:00:48,650 --> 00:00:52,280 And in general, we really want to capture the sense of you. 15 00:00:52,280 --> 00:00:54,680 I have looked at the registration list. 16 00:00:54,680 --> 00:00:57,320 We have people from every year. 17 00:00:57,320 --> 00:01:01,130 We have people from many, many different disciplines. 18 00:01:01,130 --> 00:01:04,250 So this is what we're going to do today after we I start doing 19 00:01:04,250 --> 00:01:06,310 some introductions and so on. 20 00:01:06,310 --> 00:01:08,060 We're going to talk about the nitty gritty 21 00:01:08,060 --> 00:01:09,560 of the organization. 22 00:01:09,560 --> 00:01:10,820 We need to tell you this. 23 00:01:10,820 --> 00:01:13,190 We need to convey this information to you 24 00:01:13,190 --> 00:01:17,000 clearly about when exams are, and what requirements are, 25 00:01:17,000 --> 00:01:20,480 and how to do well in this course without even realizing 26 00:01:20,480 --> 00:01:21,980 it, that kind of thing. 27 00:01:21,980 --> 00:01:25,940 And then I'll take you through this sort of fast track 28 00:01:25,940 --> 00:01:28,520 through molecules to man, all the way down 29 00:01:28,520 --> 00:01:31,250 to cells and organisms, to show you 30 00:01:31,250 --> 00:01:36,260 that there was a breakpoint in the 1950s where 31 00:01:36,260 --> 00:01:40,970 the structure, the non-covalent structure of DNA 32 00:01:40,970 --> 00:01:42,620 was elucidated. 33 00:01:42,620 --> 00:01:44,420 And there was an entire revolution 34 00:01:44,420 --> 00:01:47,870 after that which makes modern biology, the study 35 00:01:47,870 --> 00:01:52,610 of modern biology, so entirely different from the study 36 00:01:52,610 --> 00:01:55,280 of biology in the era before that. 37 00:01:55,280 --> 00:01:58,940 Biology used to be considered taxonomy and dissection, 38 00:01:58,940 --> 00:02:01,950 like listing and looking at. 39 00:02:01,950 --> 00:02:06,200 But now biology, modern biology, is a molecular science. 40 00:02:06,200 --> 00:02:10,160 So as we talk about these topics, what you will see 41 00:02:10,160 --> 00:02:14,750 is the blueprints for life are common across domains of life. 42 00:02:14,750 --> 00:02:17,240 And if you learn basic principles, 43 00:02:17,240 --> 00:02:20,510 you'll have an exponential increase in your ability 44 00:02:20,510 --> 00:02:22,780 to appreciate these characteristics, 45 00:02:22,780 --> 00:02:26,940 that modern biology is a synthesis of science, 46 00:02:26,940 --> 00:02:30,500 technology, engineering, where all the tools from those 47 00:02:30,500 --> 00:02:33,560 disciplines, different disciplines-- physics, math, 48 00:02:33,560 --> 00:02:34,850 computation-- 49 00:02:34,850 --> 00:02:39,540 funnel into modern biology to make what we know now feasible, 50 00:02:39,540 --> 00:02:44,600 and that's a dramatic and fantastic opportunity for all 51 00:02:44,600 --> 00:02:47,180 of you moving forward in your careers. 52 00:02:47,180 --> 00:02:49,500 Now I want to introduce the team. 53 00:02:49,500 --> 00:02:51,110 So I'm Barbara Imperiali. 54 00:02:51,110 --> 00:02:54,140 I'm a faculty member in chemistry and biology, 55 00:02:54,140 --> 00:02:58,160 and I'm really interested in chemical biology, 56 00:02:58,160 --> 00:03:00,350 glycobiology, biophysics. 57 00:03:00,350 --> 00:03:04,520 I love to tease apart complex pathways in organisms 58 00:03:04,520 --> 00:03:09,530 where you biosynthesize very unusual glycol conjugate that 59 00:03:09,530 --> 00:03:13,130 are very important for cell-cell communication and host cell 60 00:03:13,130 --> 00:03:15,650 pathogen communication, for example. 61 00:03:15,650 --> 00:03:17,690 I was trained as an organic chemist. 62 00:03:17,690 --> 00:03:20,840 In fact, I did my PhD degree at MIT 63 00:03:20,840 --> 00:03:24,450 about five million years ago on a sort of current scale. 64 00:03:24,450 --> 00:03:30,410 So my co-instructor is professot-- 65 00:03:30,410 --> 00:03:32,721 sorry about this, but they want us on video. 66 00:03:41,108 --> 00:03:41,900 ADAM MARTIN: Hello. 67 00:03:41,900 --> 00:03:44,900 I'm Professor Martin, and my lab is 68 00:03:44,900 --> 00:03:49,130 interested in how cells generate mechanical forces 69 00:03:49,130 --> 00:03:51,830 and how this is involved in sculpting tissues 70 00:03:51,830 --> 00:03:52,850 during development. 71 00:03:55,388 --> 00:03:57,680 BARBARA IMPERIALI: So what Adam hasn't told you is he's 72 00:03:57,680 --> 00:04:00,230 a cell biologist, a biophysicist, 73 00:04:00,230 --> 00:04:03,650 and he's a lot better at genetics than I am. 74 00:04:03,650 --> 00:04:08,540 Our instructor is Dr. Diviya Ray who's been with this course, 75 00:04:08,540 --> 00:04:11,060 now this is the sixth year, and she 76 00:04:11,060 --> 00:04:14,990 is trained in immunology, cancer biology, and also 77 00:04:14,990 --> 00:04:16,820 cellular signaling. 78 00:04:16,820 --> 00:04:18,410 But what you can't tell from that 79 00:04:18,410 --> 00:04:22,010 is how dedicated she is to each and every one of you. 80 00:04:22,010 --> 00:04:26,420 If you have any trouble in the semester, just contact Dr. Ray 81 00:04:26,420 --> 00:04:30,590 and say, I need some help, be it a particular problem 82 00:04:30,590 --> 00:04:33,260 in the material, or there's just something come up 83 00:04:33,260 --> 00:04:37,100 that makes it difficult for you to do your best in the course. 84 00:04:37,100 --> 00:04:37,940 She will help you. 85 00:04:37,940 --> 00:04:41,930 She'll work out mechanisms to get you through troubled spots. 86 00:04:41,930 --> 00:04:44,020 So let's get going here. 87 00:04:44,020 --> 00:04:47,330 Now, what I want to try to do is just 88 00:04:47,330 --> 00:04:49,820 give you sort of a flavor of where we're 89 00:04:49,820 --> 00:04:54,380 going to within the course by starting with a few bullet 90 00:04:54,380 --> 00:04:57,230 points and topics just that I can sort of 91 00:04:57,230 --> 00:04:58,830 pique your interest. 92 00:04:58,830 --> 00:05:01,700 So as I mentioned before, studying biology 93 00:05:01,700 --> 00:05:05,930 in the 21st century is a fabulous opportunity. 94 00:05:05,930 --> 00:05:09,260 No matter what discipline you come from, 95 00:05:09,260 --> 00:05:14,480 you can add to the expertise that will move biology forward. 96 00:05:14,480 --> 00:05:17,150 Biology would not be where it is today 97 00:05:17,150 --> 00:05:21,140 in the absence of science, engineering to promote it 98 00:05:21,140 --> 00:05:23,660 and to support progress in biology. 99 00:05:23,660 --> 00:05:25,360 So you really want to realize that, 100 00:05:25,360 --> 00:05:27,470 that you have an opportunity. 101 00:05:27,470 --> 00:05:30,132 You may say, well, I'm in this discipline or other. 102 00:05:30,132 --> 00:05:32,090 I don't think biology is going to have anything 103 00:05:32,090 --> 00:05:36,140 to do with my future career or career opportunities. 104 00:05:36,140 --> 00:05:38,360 But it has a lot to do with your life. 105 00:05:38,360 --> 00:05:41,540 It has a lot to do with understanding health 106 00:05:41,540 --> 00:05:45,860 and disease, understanding new scientific discoveries 107 00:05:45,860 --> 00:05:47,060 and developments. 108 00:05:47,060 --> 00:05:50,660 So it's so important that you, as a scholar 109 00:05:50,660 --> 00:05:54,830 of the 21st century, have a good grasp on these materials. 110 00:05:54,830 --> 00:05:57,650 And we're not trying to feed you anything dull and boring. 111 00:05:57,650 --> 00:06:02,450 This is really exciting stuff, because the level of complexity 112 00:06:02,450 --> 00:06:04,520 that we can study nowadays-- 113 00:06:04,520 --> 00:06:08,240 whole genomes, whole organisms at a molecular level-- 114 00:06:08,240 --> 00:06:09,900 is amazing. 115 00:06:09,900 --> 00:06:10,670 It's amazing. 116 00:06:10,670 --> 00:06:12,560 We're not just peering down a slide 117 00:06:12,560 --> 00:06:15,350 and looking at one cell or something. 118 00:06:15,350 --> 00:06:18,110 We will be able to do full descriptions. 119 00:06:18,110 --> 00:06:22,820 So what we'll try to give you is a view 120 00:06:22,820 --> 00:06:24,590 of the fundamental principles that are 121 00:06:24,590 --> 00:06:27,150 common to all living organisms. 122 00:06:27,150 --> 00:06:29,330 So the study of biology, some people 123 00:06:29,330 --> 00:06:32,480 are microbiologists, or eukaryotic biologists, 124 00:06:32,480 --> 00:06:36,770 or human biologists, or they study virology. 125 00:06:36,770 --> 00:06:39,920 But we're going to build for you, in the first few weeks 126 00:06:39,920 --> 00:06:43,430 of class, information on the common building blocks 127 00:06:43,430 --> 00:06:46,610 that go across all domains of life. 128 00:06:46,610 --> 00:06:50,270 Because once you start to learn about those molecules, 129 00:06:50,270 --> 00:06:53,180 the build up, the macromolecules of life, 130 00:06:53,180 --> 00:06:57,170 then you'll start to really gain an understanding how amazing it 131 00:06:57,170 --> 00:07:00,140 is that these same sets of molecules 132 00:07:00,140 --> 00:07:03,680 function across from bacteria to man. 133 00:07:03,680 --> 00:07:07,315 So you learn the rules for the simplest organisms. 134 00:07:07,315 --> 00:07:08,690 You look at the molecules and you 135 00:07:08,690 --> 00:07:12,680 see how form fulfills function, which is something I'm really 136 00:07:12,680 --> 00:07:14,630 excited about, and then you'll be 137 00:07:14,630 --> 00:07:19,490 able to apply it as we get ever more complex systems which 138 00:07:19,490 --> 00:07:21,740 demand a lot of attention. 139 00:07:21,740 --> 00:07:25,400 So there's a common molecular logic 140 00:07:25,400 --> 00:07:27,790 of very complex processes. 141 00:07:27,790 --> 00:07:29,900 Motivations-- I just mentioned a few. 142 00:07:29,900 --> 00:07:33,680 Sure, you want to understand health and disease. 143 00:07:33,680 --> 00:07:36,380 You want to understand what might be going on 144 00:07:36,380 --> 00:07:38,180 with current therapies. 145 00:07:38,180 --> 00:07:41,510 When you have a relative who's been diagnosed 146 00:07:41,510 --> 00:07:45,140 with a serious disease, what are the current opportunities? 147 00:07:45,140 --> 00:07:46,130 What's coming down? 148 00:07:46,130 --> 00:07:49,820 What sorts of opportunities for therapy might be available? 149 00:07:49,820 --> 00:07:51,770 Because there are so many diseases now 150 00:07:51,770 --> 00:07:54,270 we understand at a molecular level. 151 00:07:54,270 --> 00:07:57,230 We may not understand how to treat them yet, 152 00:07:57,230 --> 00:08:00,110 but we understand what their origin is, 153 00:08:00,110 --> 00:08:05,000 and that's why molecular approaches are so important. 154 00:08:05,000 --> 00:08:07,550 You may often hear of words like systems 155 00:08:07,550 --> 00:08:09,980 biology and synthetic biology. 156 00:08:09,980 --> 00:08:13,520 These are kind of jazzy words for fairly straightforward 157 00:08:13,520 --> 00:08:14,090 things. 158 00:08:14,090 --> 00:08:16,880 Systems biology is a little bit like treating 159 00:08:16,880 --> 00:08:21,710 an organism or a cell as an electrical network, a wiring 160 00:08:21,710 --> 00:08:23,360 diagram. 161 00:08:23,360 --> 00:08:25,250 What proteins talk to what proteins? 162 00:08:25,250 --> 00:08:27,050 What are downstream functions? 163 00:08:27,050 --> 00:08:28,570 Where are signals amplified? 164 00:08:28,570 --> 00:08:29,070 And so on. 165 00:08:29,070 --> 00:08:31,760 So that's systems biology at its heart, 166 00:08:31,760 --> 00:08:34,130 quantifying different intermediates 167 00:08:34,130 --> 00:08:36,530 in a complex map of the cell. 168 00:08:36,530 --> 00:08:39,679 Synthetic biology is about using biology 169 00:08:39,679 --> 00:08:42,350 to make stuff, which is really cool. 170 00:08:42,350 --> 00:08:46,020 Many, many important molecules can be made in the lab, 171 00:08:46,020 --> 00:08:49,760 but it's so much more effective to make them in an organism. 172 00:08:49,760 --> 00:08:52,520 People are doing what they call synthetic biology, 173 00:08:52,520 --> 00:08:54,680 and that's exploiting and harnessing 174 00:08:54,680 --> 00:08:57,350 nature to make things that are useful for mankind. 175 00:09:00,740 --> 00:09:02,720 And all the way through, what I just 176 00:09:02,720 --> 00:09:05,930 want to emphasize how integrating technology 177 00:09:05,930 --> 00:09:09,020 and engineering for science is really 178 00:09:09,020 --> 00:09:10,640 what we're all about here, because we 179 00:09:10,640 --> 00:09:13,400 appreciate we couldn't make the progress without it. 180 00:09:13,400 --> 00:09:17,120 There are also issues general biology impacts 181 00:09:17,120 --> 00:09:20,840 that are in the social sciences and impinge 182 00:09:20,840 --> 00:09:24,230 on things like ethics, designer babies, 183 00:09:24,230 --> 00:09:28,550 cloning people, cloning your pets, all kinds of things, 184 00:09:28,550 --> 00:09:35,020 treating a disease through genetics or not, [INAUDIBLE] 185 00:09:35,020 --> 00:09:36,950 some of these new innovations. 186 00:09:36,950 --> 00:09:38,780 But you really need to understand 187 00:09:38,780 --> 00:09:41,120 ethical issues related to them to be 188 00:09:41,120 --> 00:09:44,450 able to explain to your parents, or your grandparents, 189 00:09:44,450 --> 00:09:47,900 or your sister or brother who hasn't taken biology, what 190 00:09:47,900 --> 00:09:50,510 the implications of some of the things 191 00:09:50,510 --> 00:09:53,430 that we can do in biology, but probably we 192 00:09:53,430 --> 00:09:55,530 shouldn't do in biology. 193 00:09:55,530 --> 00:09:58,220 And we will welcome your thoughts on some of that 194 00:09:58,220 --> 00:09:59,700 later on. 195 00:09:59,700 --> 00:10:00,230 OK. 196 00:10:00,230 --> 00:10:03,110 So where did the world start? 197 00:10:03,110 --> 00:10:05,330 Arguably four and a half billion years ago 198 00:10:05,330 --> 00:10:07,250 is kind of a vague theme, but it started 199 00:10:07,250 --> 00:10:10,190 with the world, the earth, being a ball of fire, 200 00:10:10,190 --> 00:10:12,740 and it took quite a while for it to cool down 201 00:10:12,740 --> 00:10:18,140 to establish the hydrosphere and the globe as it's known today. 202 00:10:18,140 --> 00:10:21,620 There was a period of time known as the prebiotic world, where 203 00:10:21,620 --> 00:10:24,890 there were not living organisms that replicated, 204 00:10:24,890 --> 00:10:29,450 and that was basically a world where building blocks started 205 00:10:29,450 --> 00:10:33,110 to evolve out of fiery hot mud pits 206 00:10:33,110 --> 00:10:36,380 and in volcanoes and goodness knows where. 207 00:10:36,380 --> 00:10:38,510 People believe that the building blocks 208 00:10:38,510 --> 00:10:41,540 of life, just the molecules, came together 209 00:10:41,540 --> 00:10:44,300 from things like hydrogen cyanide, or sulfide, 210 00:10:44,300 --> 00:10:47,060 or other primordial components that 211 00:10:47,060 --> 00:10:49,400 were in the primordial soup. 212 00:10:49,400 --> 00:10:55,190 There was a phase known as the pre-RNA world, where the RNA 213 00:10:55,190 --> 00:10:56,600 building blocks were around. 214 00:10:56,600 --> 00:11:00,890 There's reasonable arguments in favor of the RNA world, 215 00:11:00,890 --> 00:11:03,080 where a lot of functions were catalyzed 216 00:11:03,080 --> 00:11:06,290 not by proteins, but by nucleic acids, specifically 217 00:11:06,290 --> 00:11:08,460 ribonucleic acids. 218 00:11:08,460 --> 00:11:14,870 So it's a period of time still pre-biotic 219 00:11:14,870 --> 00:11:19,160 that had the first pre-RNA, and then RNA world. 220 00:11:19,160 --> 00:11:21,800 But then things really started to get interesting 221 00:11:21,800 --> 00:11:24,710 when the first cells evolved. 222 00:11:24,710 --> 00:11:29,270 Now, I will talk a little bit about this in the next class, 223 00:11:29,270 --> 00:11:31,580 because the thing that's critical to be 224 00:11:31,580 --> 00:11:35,690 able to build a cell is to be able to build a wall around it. 225 00:11:35,690 --> 00:11:41,090 So very, very early on in life lipid bilayers, membranes, 226 00:11:41,090 --> 00:11:45,770 evolved in order to make compartmentalized structures 227 00:11:45,770 --> 00:11:48,890 where you could differentiate the in from the out. 228 00:11:48,890 --> 00:11:52,970 And so much of life is completely reliant on the fact 229 00:11:52,970 --> 00:11:54,200 that we're made of cells. 230 00:11:54,200 --> 00:11:58,100 We're not just one big sort of bucket of water with things 231 00:11:58,100 --> 00:11:59,330 floating around in it. 232 00:11:59,330 --> 00:12:02,660 Because so much of function becomes coordinated 233 00:12:02,660 --> 00:12:05,930 by cellular compartmentalization through things 234 00:12:05,930 --> 00:12:10,070 known as lipid bilayers, which are semi-permeable membranes. 235 00:12:10,070 --> 00:12:11,870 Oxygen can move across. 236 00:12:11,870 --> 00:12:14,810 Some small hydrophobic things can move across. 237 00:12:14,810 --> 00:12:18,050 But a lot of things get either stuck in or stuck out. 238 00:12:18,050 --> 00:12:19,800 So we'll talk a lot about that. 239 00:12:19,800 --> 00:12:22,820 So the first prokaryotes were cyanobacteria. 240 00:12:22,820 --> 00:12:24,980 They're photosynthetic bacteria. 241 00:12:24,980 --> 00:12:30,200 It was quite a long time until those unicellular organisms 242 00:12:30,200 --> 00:12:33,680 that totally lacked a nucleus, lacked a lot of intracellular 243 00:12:33,680 --> 00:12:37,580 compartmentalization, evolved to eukaryotes, 244 00:12:37,580 --> 00:12:39,630 and those cells are different. 245 00:12:39,630 --> 00:12:42,890 They're 100 or 1,000 times bigger. 246 00:12:42,890 --> 00:12:43,970 They're complex. 247 00:12:43,970 --> 00:12:45,710 They're compartmentalized. 248 00:12:45,710 --> 00:12:47,600 They can do a lot of functions. 249 00:12:47,600 --> 00:12:51,710 In a full organism they're very differentiated, 250 00:12:51,710 --> 00:12:55,070 and they may look different in muscle, or in heart, 251 00:12:55,070 --> 00:12:57,120 or in skin, or in bone. 252 00:12:57,120 --> 00:13:01,020 And so those eukaryotes-- so that's a long gap of time, 253 00:13:01,020 --> 00:13:03,440 but there was a lot going on in that phase. 254 00:13:03,440 --> 00:13:06,620 And about a half a billion years ago, multicellular life 255 00:13:06,620 --> 00:13:07,550 evolved. 256 00:13:07,550 --> 00:13:10,250 And multicellular life now can be looked at, 257 00:13:10,250 --> 00:13:13,070 if we think of the evolution of homo sapiens, 258 00:13:13,070 --> 00:13:17,000 can be thought of as something that we can keep track of a bit 259 00:13:17,000 --> 00:13:21,260 through fossil records over the last five million years, 260 00:13:21,260 --> 00:13:23,900 where the first humanoid life evolved. 261 00:13:23,900 --> 00:13:25,520 Then you got sort of to a stage-- 262 00:13:25,520 --> 00:13:29,750 I think he's homo ergaster, that this sort of Shrek-like person 263 00:13:29,750 --> 00:13:31,680 evolved quite early on. 264 00:13:31,680 --> 00:13:37,400 And then the humanoids gradually became different, evolved. 265 00:13:37,400 --> 00:13:39,710 In some cases there were branches of the tree 266 00:13:39,710 --> 00:13:41,750 of evolution and dead ends. 267 00:13:41,750 --> 00:13:44,060 In other places there was a branch 268 00:13:44,060 --> 00:13:45,410 that carried on for a while. 269 00:13:45,410 --> 00:13:49,160 For example, the neanderthal and homo sapiens kind of 270 00:13:49,160 --> 00:13:51,170 kept on evolving for a while. 271 00:13:51,170 --> 00:13:52,820 But there's a lot of developments 272 00:13:52,820 --> 00:13:55,730 that have been characterized from the fossil record. 273 00:13:55,730 --> 00:13:59,360 But now there's a lot of belief that if we trace things back 274 00:13:59,360 --> 00:14:03,170 through genomes, we might get more precise information 275 00:14:03,170 --> 00:14:05,310 on steps in evolution. 276 00:14:05,310 --> 00:14:09,620 Now, the evolution of the advanced, if you will, 277 00:14:09,620 --> 00:14:13,170 hominids really came along with a number of things. 278 00:14:13,170 --> 00:14:17,150 There was a stage at which a particular gene, the FOXP gene, 279 00:14:17,150 --> 00:14:21,400 is attributed to the ability for complex speech. 280 00:14:21,400 --> 00:14:24,320 And that could have been a leap forward when humanoids 281 00:14:24,320 --> 00:14:26,510 could communicate more, and it seems 282 00:14:26,510 --> 00:14:28,520 to be associated with that. 283 00:14:28,520 --> 00:14:31,250 But there are other sort of sociological functions, 284 00:14:31,250 --> 00:14:34,160 like burying the dead, or making jewelry, 285 00:14:34,160 --> 00:14:37,670 or making tools, that are associated with the more 286 00:14:37,670 --> 00:14:39,350 evolved organisms. 287 00:14:39,350 --> 00:14:43,580 There are other types of things like cranial capacity, standing 288 00:14:43,580 --> 00:14:45,380 upright, looking forward. 289 00:14:45,380 --> 00:14:50,000 A lot of things came through those years of the evolution 290 00:14:50,000 --> 00:14:51,960 of homo sapiens. 291 00:14:51,960 --> 00:14:54,410 So it's fascinating to think about that 292 00:14:54,410 --> 00:14:58,490 and to think what light genetics can shed on those five 293 00:14:58,490 --> 00:15:01,280 million years of evolution. 294 00:15:01,280 --> 00:15:06,710 Now, the world of biology took a mega kick start 295 00:15:06,710 --> 00:15:10,050 with the elucidation of the human genome, 296 00:15:10,050 --> 00:15:12,140 but more importantly of the technology 297 00:15:12,140 --> 00:15:17,820 necessary to solve the map of the whole human genome. 298 00:15:17,820 --> 00:15:21,030 In 2001 there was a major development 299 00:15:21,030 --> 00:15:24,450 with the publication of the first map of the human genome. 300 00:15:24,450 --> 00:15:27,540 It's fascinating to think with humans, 301 00:15:27,540 --> 00:15:31,680 we humans have about three billion genes, 302 00:15:31,680 --> 00:15:34,070 but there's only across human-- 303 00:15:34,070 --> 00:15:34,680 is that right? 304 00:15:34,680 --> 00:15:35,460 No, sorry. 305 00:15:35,460 --> 00:15:36,780 Base pairs, yes. 306 00:15:36,780 --> 00:15:38,190 Thank you very much. 307 00:15:38,190 --> 00:15:42,420 But across humankind there's enormous diversity, 308 00:15:42,420 --> 00:15:49,420 but that's accounted for by only about 0.1% of the diversity. 309 00:15:49,420 --> 00:15:52,450 So you can see people look very, very different, 310 00:15:52,450 --> 00:15:57,210 but we still share 99.9% of our genome. 311 00:15:57,210 --> 00:16:00,660 Another very interesting thing is that genomes vary in size 312 00:16:00,660 --> 00:16:03,413 quite considerably. 313 00:16:03,413 --> 00:16:04,830 Before I move forward, I just want 314 00:16:04,830 --> 00:16:07,320 to quickly show you this map. 315 00:16:07,320 --> 00:16:15,120 I mentioned tracing evolution through a molecular clock, 316 00:16:15,120 --> 00:16:19,230 so looking back in time not by following the shape of a skull, 317 00:16:19,230 --> 00:16:22,020 for example, or physiologic changes, 318 00:16:22,020 --> 00:16:26,340 but looking at genomes using the genome as a molecular clock 319 00:16:26,340 --> 00:16:30,090 based on mutation rates that are fairly constant amongst domains 320 00:16:30,090 --> 00:16:30,750 of life. 321 00:16:30,750 --> 00:16:33,570 You couldn't compare a human and a bacterium, 322 00:16:33,570 --> 00:16:37,050 but you can go back through a lot of eukaryotic evolution 323 00:16:37,050 --> 00:16:39,340 and see where divergence has happened. 324 00:16:39,340 --> 00:16:44,280 So in this map, you can see that human and neanderthal diverged 325 00:16:44,280 --> 00:16:47,010 from the chimpanzee a certain time ago, 326 00:16:47,010 --> 00:16:50,430 which had diverged from the gorilla further ago based 327 00:16:50,430 --> 00:16:53,650 on the molecular clock that's available. 328 00:16:53,650 --> 00:16:54,390 OK. 329 00:16:54,390 --> 00:16:56,550 So now I want to talk a little bit more 330 00:16:56,550 --> 00:16:59,460 about getting into the details of the genome. 331 00:16:59,460 --> 00:17:02,610 So genomes differ greatly in size. 332 00:17:02,610 --> 00:17:06,450 Our genome includes about three billion base pairs 333 00:17:06,450 --> 00:17:10,589 in our 22 chromosomes plus the X and Y chromosome, 334 00:17:10,589 --> 00:17:13,530 but the typical genome of a model bacterium 335 00:17:13,530 --> 00:17:16,150 has only five million base pairs. 336 00:17:16,150 --> 00:17:19,240 So far, far smaller, more tangible, 337 00:17:19,240 --> 00:17:21,900 more easy to study, because those genes 338 00:17:21,900 --> 00:17:25,560 are more limited in size, but the genome size 339 00:17:25,560 --> 00:17:28,500 is not necessarily proportionate to the number 340 00:17:28,500 --> 00:17:31,890 of genes that are expressed and made into proteins. 341 00:17:31,890 --> 00:17:37,830 A fascinating discovery is that of the three billion base 342 00:17:37,830 --> 00:17:43,950 pairs, only about 1.5% to 2% actually code for proteins, 343 00:17:43,950 --> 00:17:45,920 and there's a ton of interest now 344 00:17:45,920 --> 00:17:49,320 in what's the rest of the genome doing there. 345 00:17:49,320 --> 00:17:50,530 Where did it come from? 346 00:17:50,530 --> 00:17:51,663 What's its function? 347 00:17:51,663 --> 00:17:53,580 There are different functions that Eric Lander 348 00:17:53,580 --> 00:17:56,910 calls the dark matter of the genome, different functions 349 00:17:56,910 --> 00:17:58,650 to the rest of the genome. 350 00:17:58,650 --> 00:18:01,050 But the part that we focus on is the part 351 00:18:01,050 --> 00:18:03,870 that gets encoded into proteins that 352 00:18:03,870 --> 00:18:06,250 form the functions of the molecules of life. 353 00:18:06,250 --> 00:18:08,650 So we're going to focus ourselves in on those. 354 00:18:08,650 --> 00:18:12,240 But here you see differences in sizes of genomes 355 00:18:12,240 --> 00:18:13,930 based on base pair. 356 00:18:13,930 --> 00:18:17,490 But what's fascinating is despite this huge breadth 357 00:18:17,490 --> 00:18:21,960 of sizes and huge differences in organisms, 358 00:18:21,960 --> 00:18:23,610 the building blocks are the same. 359 00:18:23,610 --> 00:18:27,570 And that's what I think is the wonderful part of what we're 360 00:18:27,570 --> 00:18:32,610 able to teach you is, we can take you from the 1950s 361 00:18:32,610 --> 00:18:37,170 when the structure of double stranded DNA was first solved. 362 00:18:37,170 --> 00:18:39,810 Now, there were 60, 70, or more years of work 363 00:18:39,810 --> 00:18:42,630 before that where they figured out the pieces, 364 00:18:42,630 --> 00:18:45,090 they figured out the chemistry, the covalent bonds, 365 00:18:45,090 --> 00:18:48,120 and the bases, and the sugars, and the phosphodiester. 366 00:18:48,120 --> 00:18:54,240 But they had no clue how the DNA could encode and program 367 00:18:54,240 --> 00:18:56,310 the synthesis of a protein. 368 00:18:56,310 --> 00:19:01,380 But once the structure, the three-dimensional structure 369 00:19:01,380 --> 00:19:03,840 of double-stranded DNA was solved-- 370 00:19:03,840 --> 00:19:06,630 this is this beautiful anti-parallel structure that 371 00:19:06,630 --> 00:19:07,800 you see here-- 372 00:19:07,800 --> 00:19:11,070 by Watson, Crick, and Rosalind Franklin, 373 00:19:11,070 --> 00:19:14,198 then the clues came pouring in. 374 00:19:14,198 --> 00:19:16,740 Without that structure, without the structure of what's known 375 00:19:16,740 --> 00:19:20,250 as the non-covalent structure-- not the covalent structure, 376 00:19:20,250 --> 00:19:22,000 you'll see all those building blocks-- 377 00:19:22,000 --> 00:19:23,580 but the non-covalent structure, how 378 00:19:23,580 --> 00:19:27,000 you could zipper apart the two strands of DNA 379 00:19:27,000 --> 00:19:30,480 and make copies of both of them and replicate DNA and then 380 00:19:30,480 --> 00:19:31,450 go forward. 381 00:19:31,450 --> 00:19:33,750 That was an amazing step forward, 382 00:19:33,750 --> 00:19:36,360 and for that, there was a Nobel Prize awarded. 383 00:19:36,360 --> 00:19:38,550 Unfortunately it was after Franklin's death. 384 00:19:38,550 --> 00:19:44,260 So it was given to Watson and Crick and a third person. 385 00:19:44,260 --> 00:19:46,780 Now, here's has that structure of DNA. 386 00:19:46,780 --> 00:19:49,960 I could sort of watch it for hours to be honest. 387 00:19:49,960 --> 00:19:53,620 The phosphodiester background-- backbone going up the back, 388 00:19:53,620 --> 00:19:56,130 and the bases base pairing across. 389 00:19:56,130 --> 00:19:59,290 And these are the key steps that happened from the '50s. 390 00:19:59,290 --> 00:20:01,900 So in the definite-- after the definition 391 00:20:01,900 --> 00:20:06,140 of the double stranded structure, it took a few years, 392 00:20:06,140 --> 00:20:09,290 but they cracked what's known as the genetic code. 393 00:20:09,290 --> 00:20:13,930 How does that DNA get converted into a protein? 394 00:20:13,930 --> 00:20:17,260 What happens is you make an RNA copy of the DNA. 395 00:20:17,260 --> 00:20:20,110 And the RNA is read to make a protein. 396 00:20:20,110 --> 00:20:22,600 And you will learn about all those components. 397 00:20:22,600 --> 00:20:25,060 But that was another real landmark. 398 00:20:25,060 --> 00:20:28,240 Then what was really exciting is that some technology 399 00:20:28,240 --> 00:20:31,390 companies started figuring out, first, there 400 00:20:31,390 --> 00:20:34,750 were very slow ways to sequence DNA. 401 00:20:34,750 --> 00:20:38,560 But in the-- and that happened in 1977. 402 00:20:38,560 --> 00:20:41,950 But what was really important is about a decade later, 403 00:20:41,950 --> 00:20:44,140 where the ability to sequence DNA 404 00:20:44,140 --> 00:20:47,680 was not done anymore using huge agarose gels 405 00:20:47,680 --> 00:20:49,570 and a bucket of radioactivity. 406 00:20:49,570 --> 00:20:52,090 But it was done through using fluorescence, 407 00:20:52,090 --> 00:20:56,560 in order to allow you to read out the sequence of DNA. 408 00:20:56,560 --> 00:20:58,750 And you will learn about that. 409 00:20:58,750 --> 00:21:01,900 And in 1987, the instruments were 410 00:21:01,900 --> 00:21:05,770 commercialized, major, major technology and engineering. 411 00:21:05,770 --> 00:21:08,110 We wouldn't be anywhere without that. 412 00:21:08,110 --> 00:21:11,620 In 1990, the Human Genome Project began. 413 00:21:11,620 --> 00:21:16,300 In '01, the draft of the human genome sequence was completed. 414 00:21:16,300 --> 00:21:18,940 2010, you could sequence a single strand 415 00:21:18,940 --> 00:21:21,940 of DNA, one molecule of DNA. 416 00:21:21,940 --> 00:21:23,530 And now there's so many initiatives 417 00:21:23,530 --> 00:21:24,680 that have come out of that. 418 00:21:24,680 --> 00:21:27,550 And so much amazing technology that has evolved. 419 00:21:27,550 --> 00:21:30,760 So things like the 1,000 Genomes Project 420 00:21:30,760 --> 00:21:34,757 to look at variation across man, so all people 421 00:21:34,757 --> 00:21:36,340 from all different parts of the world. 422 00:21:36,340 --> 00:21:37,660 You can look up that website. 423 00:21:37,660 --> 00:21:39,760 That's very cool. 424 00:21:39,760 --> 00:21:42,310 The Human Cell Atlas, there was quite a bit of news 425 00:21:42,310 --> 00:21:45,460 about that in MIT Technology News, 426 00:21:45,460 --> 00:21:49,420 where Aviv Regev is playing a major part in that, 427 00:21:49,420 --> 00:21:52,210 to actually sequence representatives 428 00:21:52,210 --> 00:21:58,210 from all of your trillions of cells and see how they differ. 429 00:21:58,210 --> 00:22:02,710 And then there's cancer genome projects and precision medicine 430 00:22:02,710 --> 00:22:05,710 sequence every type of cancer cell, 431 00:22:05,710 --> 00:22:07,540 find out what's different about it, 432 00:22:07,540 --> 00:22:09,940 and precisely figure out how to treat 433 00:22:09,940 --> 00:22:12,130 it, all very exciting things. 434 00:22:12,130 --> 00:22:14,620 And then of course, there's synthetic genomes, where 435 00:22:14,620 --> 00:22:17,410 you can literally build a cell and its genome, 436 00:22:17,410 --> 00:22:20,163 program it to do what you want, hopefully. 437 00:22:20,163 --> 00:22:21,580 And then there's one of the things 438 00:22:21,580 --> 00:22:23,413 that your generation will have to deal with, 439 00:22:23,413 --> 00:22:24,640 and that's all the data. 440 00:22:24,640 --> 00:22:27,640 Because we've just found ways to churn it out. 441 00:22:27,640 --> 00:22:30,730 But you guys are going to have to do the heavy lifting there. 442 00:22:30,730 --> 00:22:34,720 So DNA, then, looking at that structure, 443 00:22:34,720 --> 00:22:37,150 is packaged into cells. 444 00:22:37,150 --> 00:22:39,340 So figure this one out. 445 00:22:39,340 --> 00:22:44,740 Each human cell has 1.8 meters of DNA in it, 446 00:22:44,740 --> 00:22:49,900 yet it fits into a cell that's 10 to 100 microns in diameter. 447 00:22:49,900 --> 00:22:52,090 And it's bundled tightly up. 448 00:22:52,090 --> 00:22:56,500 So you'll learn how DNA in cells gets bundled up and wrapped 449 00:22:56,500 --> 00:23:00,100 around proteins that neutralize the negative charges 450 00:23:00,100 --> 00:23:03,970 of the double stranded DNA with positively charged proteins 451 00:23:03,970 --> 00:23:05,470 and enable packaging. 452 00:23:05,470 --> 00:23:07,690 So we will talk about all of this. 453 00:23:07,690 --> 00:23:09,640 When is DNA unraveled? 454 00:23:09,640 --> 00:23:11,860 What signals its unraveling? 455 00:23:11,860 --> 00:23:15,130 Because in order to copy it, you've got to unpack it. 456 00:23:15,130 --> 00:23:18,310 So these are a lot of details about DNA 457 00:23:18,310 --> 00:23:21,040 that you'll be able to sort of have much more sense of as we 458 00:23:21,040 --> 00:23:23,620 move forward. 459 00:23:23,620 --> 00:23:25,870 Cells are different in size. 460 00:23:25,870 --> 00:23:30,070 I just mentioned to you a typical eukaryotic cell 461 00:23:30,070 --> 00:23:34,840 is about 10 to 100 microns in diameter. 462 00:23:34,840 --> 00:23:38,950 A typical bacterial cell is about 1 to 10 microns. 463 00:23:38,950 --> 00:23:41,380 So there is a vast difference in sizes 464 00:23:41,380 --> 00:23:44,860 for these simple cells that have no nucleus, 465 00:23:44,860 --> 00:23:48,580 relative to the cells that are compartmentalized 466 00:23:48,580 --> 00:23:50,470 and perform a lot of functions. 467 00:23:50,470 --> 00:23:54,190 So we will learn to appreciate that difference in size, 468 00:23:54,190 --> 00:23:57,010 looking at the building blocks that go into all of them, 469 00:23:57,010 --> 00:24:00,700 but then understanding how big cells have 470 00:24:00,700 --> 00:24:04,210 to have a lot more complexity in their signaling 471 00:24:04,210 --> 00:24:06,580 in order to establish their functions 472 00:24:06,580 --> 00:24:09,970 but also interact with other cells in multicellular 473 00:24:09,970 --> 00:24:11,920 organisms. 474 00:24:11,920 --> 00:24:14,380 We're still doing fine for time, yes. 475 00:24:14,380 --> 00:24:17,500 The other thing that we will spend several classes on 476 00:24:17,500 --> 00:24:21,820 is imaging and visualization of things going on in cells. 477 00:24:21,820 --> 00:24:24,640 So what we'll talk to you about is the discovery 478 00:24:24,640 --> 00:24:27,670 of fluorescent proteins, which have provided 479 00:24:27,670 --> 00:24:31,150 an unparalleled opportunity to label proteins 480 00:24:31,150 --> 00:24:35,050 within living organisms in order to track what they do. 481 00:24:35,050 --> 00:24:37,630 And through the efforts of protein engineers, 482 00:24:37,630 --> 00:24:41,050 there is an entire panel of colored proteins that 483 00:24:41,050 --> 00:24:42,610 fluoresce at different wavelengths 484 00:24:42,610 --> 00:24:48,910 that we can use to study biology in live systems, in real time. 485 00:24:48,910 --> 00:24:51,180 These slides show you a little bit of that. 486 00:24:51,180 --> 00:24:54,600 I love these pictures, just showing a dividing cell. 487 00:24:54,600 --> 00:24:58,080 Where the chromosomes you see red because the histones 488 00:24:58,080 --> 00:25:00,420 are labeled with red fluorescent protein, 489 00:25:00,420 --> 00:25:04,260 and all that green fuzzy stuff are microtubules around. 490 00:25:04,260 --> 00:25:05,250 We can do this now. 491 00:25:05,250 --> 00:25:09,960 You couldn't do this 15 years ago, observe these changes. 492 00:25:09,960 --> 00:25:13,110 We can also look at changes as cells divide and go 493 00:25:13,110 --> 00:25:14,610 through the cell cycle. 494 00:25:14,610 --> 00:25:17,470 One of my favorites is this where 495 00:25:17,470 --> 00:25:21,420 of going through the stages to program a cell to divide, 496 00:25:21,420 --> 00:25:24,390 a new protein gets made, and then it settles down. 497 00:25:24,390 --> 00:25:28,170 But then when you go to divide again, you keep making-- 498 00:25:28,170 --> 00:25:32,160 you cyclically make different sets of proteins. 499 00:25:32,160 --> 00:25:36,060 And you can observe them in real time dividing. 500 00:25:36,060 --> 00:25:38,790 So just think if you were trying to make a chemotherapeutic 501 00:25:38,790 --> 00:25:40,980 where you wanted to stop cell division, 502 00:25:40,980 --> 00:25:43,830 or you wanted to inhibit one of those proteins, 503 00:25:43,830 --> 00:25:46,170 you could literally watch it function. 504 00:25:46,170 --> 00:25:47,490 Does it get in to cell? 505 00:25:47,490 --> 00:25:50,980 Does it disrupt the normal pattern of cell division? 506 00:25:50,980 --> 00:25:55,713 So these are capabilities that are now, really are available. 507 00:25:55,713 --> 00:25:57,130 So I've talked to you about cells. 508 00:25:57,130 --> 00:26:00,210 But I'm going to pass you over to Professor Martin 509 00:26:00,210 --> 00:26:03,255 for a little bit-- you'll get a little bit of a sense of how 510 00:26:03,255 --> 00:26:03,840 he thinks. 511 00:26:07,580 --> 00:26:10,480 And then I'll do the wrap up. 512 00:26:10,480 --> 00:26:12,170 PROFESSOR MARTIN: Thank you. 513 00:26:12,170 --> 00:26:16,340 So this is one of my favorite model organisms. 514 00:26:16,340 --> 00:26:22,270 This is a fruit fly, at larger than real size. 515 00:26:22,270 --> 00:26:27,970 And so one topic that I'll start on when 516 00:26:27,970 --> 00:26:32,140 I start lecturing either at the end of this month 517 00:26:32,140 --> 00:26:36,040 or beginning of October is we'll talk a lot about genetics. 518 00:26:36,040 --> 00:26:39,640 And one thing we'll start on is pioneering research 519 00:26:39,640 --> 00:26:43,900 done in this system to establish the chromosome 520 00:26:43,900 --> 00:26:45,790 theory of inheritance. 521 00:26:45,790 --> 00:26:46,740 OK. 522 00:26:46,740 --> 00:26:50,140 And we'll talk about the importance in model organisms 523 00:26:50,140 --> 00:26:52,900 in discovering new biology. 524 00:26:52,900 --> 00:26:55,150 But in addition to that, I also want 525 00:26:55,150 --> 00:27:00,280 to talk about how genetics will affect you guys as you go on 526 00:27:00,280 --> 00:27:05,020 and graduate from MIT and go into your own careers. 527 00:27:05,020 --> 00:27:08,440 Because genetics is really playing an important role 528 00:27:08,440 --> 00:27:10,270 in all our lives. 529 00:27:10,270 --> 00:27:14,170 And already, you guys have the option 530 00:27:14,170 --> 00:27:17,310 to get your DNA genotyped, right. 531 00:27:17,310 --> 00:27:23,140 There are lots of companies now like 23andMe and Ancestry.com 532 00:27:23,140 --> 00:27:25,270 where you can get your DNA genotyped. 533 00:27:25,270 --> 00:27:28,660 And you can learn about your ancestry. 534 00:27:28,660 --> 00:27:32,050 You can learn about whether you might be predisposed 535 00:27:32,050 --> 00:27:34,790 towards certain diseases. 536 00:27:34,790 --> 00:27:40,480 And so in order to appreciate the data you get back 537 00:27:40,480 --> 00:27:43,240 from these companies, you really have to understand something 538 00:27:43,240 --> 00:27:44,740 about genetics. 539 00:27:44,740 --> 00:27:47,250 And another thing which I find very fascinating 540 00:27:47,250 --> 00:27:51,860 are ethical issues that come up with the use of such sites. 541 00:27:51,860 --> 00:27:56,890 And you might have seen this in the news last semester. 542 00:27:56,890 --> 00:28:01,330 Both forensic experts and police identified 543 00:28:01,330 --> 00:28:05,410 a suspect in a killing that happened 40 years ago. 544 00:28:05,410 --> 00:28:11,650 And this was in part due to using the suspect's family 545 00:28:11,650 --> 00:28:12,430 tree. 546 00:28:12,430 --> 00:28:13,690 OK. 547 00:28:13,690 --> 00:28:16,760 And so they used the family tree, you know, some-- 548 00:28:16,760 --> 00:28:19,720 you know, this guy's relatives had done one of these 549 00:28:19,720 --> 00:28:20,350 Ancestry.com's. 550 00:28:20,350 --> 00:28:25,810 And they used the information from DNA 551 00:28:25,810 --> 00:28:28,330 acquired from other individuals to track down 552 00:28:28,330 --> 00:28:30,130 this other individual. 553 00:28:30,130 --> 00:28:32,150 OK. 554 00:28:32,150 --> 00:28:35,030 So one thing that I find incredibly exciting 555 00:28:35,030 --> 00:28:39,260 about biology is that it is truly dynamic. 556 00:28:39,260 --> 00:28:40,160 OK. 557 00:28:40,160 --> 00:28:42,260 And this is a human neutrophil. 558 00:28:42,260 --> 00:28:44,700 And it's just a bright field microscopy. 559 00:28:44,700 --> 00:28:46,370 Nothing's labeled. 560 00:28:46,370 --> 00:28:49,660 And what you're seeing here is this-- 561 00:28:49,660 --> 00:28:52,930 this neutrophil is chasing after this bacterium. 562 00:28:52,930 --> 00:28:55,600 And it illustrates another concept 563 00:28:55,600 --> 00:28:59,290 that we'll talk about in this course, which is signaling. 564 00:28:59,290 --> 00:29:02,440 So this neutrophil is receiving a signal 565 00:29:02,440 --> 00:29:05,800 from this bacteria that tells it where it is. 566 00:29:05,800 --> 00:29:10,230 And it's then able to chase that bacterium and track it down. 567 00:29:10,230 --> 00:29:12,870 And there you see it just got the bacterium. 568 00:29:12,870 --> 00:29:13,990 OK. 569 00:29:13,990 --> 00:29:19,000 So we'll talk about dynamic processes that cells do 570 00:29:19,000 --> 00:29:23,200 and how that's important for their function. 571 00:29:23,200 --> 00:29:25,880 In addition to considering single cells, 572 00:29:25,880 --> 00:29:28,660 we also want to understand how entire organisms 573 00:29:28,660 --> 00:29:30,370 and tissues work. 574 00:29:30,370 --> 00:29:32,950 And I want to emphasize that, yes, 575 00:29:32,950 --> 00:29:36,700 we have sequence-- or researchers have sequenced 576 00:29:36,700 --> 00:29:41,080 the human genome and the genomes of many different organisms, 577 00:29:41,080 --> 00:29:41,890 OK. 578 00:29:41,890 --> 00:29:43,210 And that's great, right. 579 00:29:43,210 --> 00:29:45,790 We have this data set. 580 00:29:45,790 --> 00:29:50,080 But we still don't understand how all the components that 581 00:29:50,080 --> 00:29:52,900 are in the genome are wired together 582 00:29:52,900 --> 00:29:56,500 and work in order to create a complicated organism 583 00:29:56,500 --> 00:29:57,900 like ourselves. 584 00:29:57,900 --> 00:29:58,720 OK. 585 00:29:58,720 --> 00:30:01,660 And so one aspect of that, which is mysterious, 586 00:30:01,660 --> 00:30:04,890 is how does the genome encode shape? 587 00:30:04,890 --> 00:30:05,590 OK. 588 00:30:05,590 --> 00:30:07,900 How do we get our shape, and how do we 589 00:30:07,900 --> 00:30:09,980 get the shape of our organs? 590 00:30:09,980 --> 00:30:12,940 And this is something that my lab is interested in. 591 00:30:12,940 --> 00:30:17,400 And so this is a fruit fly embryo. 592 00:30:17,400 --> 00:30:19,830 And you can see at the beginning here, 593 00:30:19,830 --> 00:30:22,260 this is three hours into development. 594 00:30:22,260 --> 00:30:26,190 You just have a smooth surface for this embryo. 595 00:30:26,190 --> 00:30:29,760 But during development, this changes. 596 00:30:29,760 --> 00:30:32,520 And I'm just showing you here a cross-section 597 00:30:32,520 --> 00:30:33,470 of the same embryo. 598 00:30:33,470 --> 00:30:35,130 And you see, it's a sheet of cells 599 00:30:35,130 --> 00:30:37,480 that surrounds a central yolk. 600 00:30:37,480 --> 00:30:37,980 OK. 601 00:30:37,980 --> 00:30:41,070 And this changes three hours into development, 602 00:30:41,070 --> 00:30:47,570 because a population of about 1,000 cells in this organism 603 00:30:47,570 --> 00:30:49,260 fold to form a crease. 604 00:30:49,260 --> 00:30:49,760 OK. 605 00:30:49,760 --> 00:30:52,490 So this is a dramatic shape change for this embryo. 606 00:30:52,490 --> 00:30:54,740 It goes from being a single layer 607 00:30:54,740 --> 00:30:56,910 to now having multiple layers. 608 00:30:56,910 --> 00:30:59,810 So this is a time course here, showing you 609 00:30:59,810 --> 00:31:02,630 how cells change shape in this tissue 610 00:31:02,630 --> 00:31:05,030 and how this leads to what's initially 611 00:31:05,030 --> 00:31:09,440 a single layer of cells to become two layers of cells. 612 00:31:09,440 --> 00:31:13,820 And this process is similar to morphogenetic events 613 00:31:13,820 --> 00:31:16,160 that happen in human embryos. 614 00:31:16,160 --> 00:31:21,350 But we can study this in fruit fly embryos or many other model 615 00:31:21,350 --> 00:31:25,430 systems, in order to try to understand mechanistically 616 00:31:25,430 --> 00:31:26,150 how this happens. 617 00:31:30,120 --> 00:31:31,490 So again, this is dynamic. 618 00:31:31,490 --> 00:31:33,830 And I want to show you a movie that shows you 619 00:31:33,830 --> 00:31:36,670 the dynamics of this process. 620 00:31:36,670 --> 00:31:39,620 So now this is an embryo that's been labeled 621 00:31:39,620 --> 00:31:41,540 with some of these fluorescent proteins 622 00:31:41,540 --> 00:31:44,400 that Professor Imperiali just introduced. 623 00:31:44,400 --> 00:31:46,730 One's green, that's the-- 624 00:31:46,730 --> 00:31:48,080 and it's shown here in green. 625 00:31:48,080 --> 00:31:50,810 And the other is a red fluorescent protein in red. 626 00:31:50,810 --> 00:31:54,410 The red fluorescent protein is marking individual cells. 627 00:31:54,410 --> 00:31:58,280 The green protein is a motor protein that generates force. 628 00:31:58,280 --> 00:32:02,360 And what you see is, where the motor protein is, 629 00:32:02,360 --> 00:32:04,910 this is where the tissue contracts. 630 00:32:04,910 --> 00:32:07,150 And this is where the tissue folds. 631 00:32:07,150 --> 00:32:08,270 OK. 632 00:32:08,270 --> 00:32:12,410 And so because we're able to see these proteins in action, 633 00:32:12,410 --> 00:32:16,110 we can infer how they're functioning during development 634 00:32:16,110 --> 00:32:22,470 to essentially program tissue shape. 635 00:32:22,470 --> 00:32:24,540 And there are many other opportunities 636 00:32:24,540 --> 00:32:26,880 where, even though we have the genome, 637 00:32:26,880 --> 00:32:31,170 we still don't understand how collectives of proteins, 638 00:32:31,170 --> 00:32:34,380 or collectives of cells, are sort of interacting 639 00:32:34,380 --> 00:32:39,600 with each other to sort of create emergent properties that 640 00:32:39,600 --> 00:32:43,080 are what are responsible for patterning something 641 00:32:43,080 --> 00:32:46,540 as large as a human. 642 00:32:46,540 --> 00:32:50,050 Another thing that we'll talk about is how cells divide. 643 00:32:50,050 --> 00:32:52,450 And this is another fruit fly embryo. 644 00:32:52,450 --> 00:32:54,940 And it's labeling histones. 645 00:32:54,940 --> 00:32:57,040 So it labels the DNA. 646 00:32:57,040 --> 00:33:01,920 And so you're seeing nuclei here divide sequentially. 647 00:33:01,920 --> 00:33:03,490 There'll be one more division. 648 00:33:03,490 --> 00:33:04,730 And then it's going to stop. 649 00:33:04,730 --> 00:33:05,230 OK. 650 00:33:05,230 --> 00:33:08,170 And my point here is that cell division 651 00:33:08,170 --> 00:33:12,850 during development and in adults is under exquisite control. 652 00:33:12,850 --> 00:33:14,320 OK. 653 00:33:14,320 --> 00:33:16,930 And a breakdown of this control is 654 00:33:16,930 --> 00:33:19,550 important in the progression of cancer. 655 00:33:19,550 --> 00:33:23,860 So we're going to talk about how cells control whether or not 656 00:33:23,860 --> 00:33:29,920 they divide, and how this is impacted in cancer cells. 657 00:33:29,920 --> 00:33:32,530 I also want to point out that this video is 658 00:33:32,530 --> 00:33:37,284 from Eric Wieschaus who is at Princeton University. 659 00:33:40,740 --> 00:33:41,240 OK. 660 00:33:41,240 --> 00:33:42,407 Want to just hit the lights. 661 00:33:42,407 --> 00:33:45,580 I have one last thing just to mention. 662 00:33:45,580 --> 00:33:48,970 So I just want to reinforce what Professor Imperiali said, 663 00:33:48,970 --> 00:33:50,740 we have a small class. 664 00:33:50,740 --> 00:33:53,770 So this is really an opportunity to have 665 00:33:53,770 --> 00:33:57,520 this be more interactive than it would be if we had 666 00:33:57,520 --> 00:34:00,230 like 300 people in the class. 667 00:34:00,230 --> 00:34:06,070 So I want to really encourage you guys to ask questions. 668 00:34:06,070 --> 00:34:09,350 Also if you have ideas, we would love to hear them. 669 00:34:09,350 --> 00:34:14,199 And I want to try one new thing this semester. 670 00:34:14,199 --> 00:34:16,690 So I find that students are a little hesitant 671 00:34:16,690 --> 00:34:18,610 to come to my office hours. 672 00:34:18,610 --> 00:34:23,000 So this year I want to hold what I'm calling running hours. 673 00:34:26,190 --> 00:34:30,560 So one thing that I really like to do is I like to run. 674 00:34:30,560 --> 00:34:33,949 And I've noticed that many of my students 675 00:34:33,949 --> 00:34:36,650 are also runners, because I'll like see them out 676 00:34:36,650 --> 00:34:38,300 around the river. 677 00:34:38,300 --> 00:34:42,920 And so I just want to hold sort of weekly running hours. 678 00:34:42,920 --> 00:34:48,580 I'm going to choose 3 o'clock, not three hour run, all right, 679 00:34:48,580 --> 00:34:52,000 3:00 PM on Fridays. 680 00:34:52,000 --> 00:34:53,450 And we'll just meet in my office. 681 00:34:57,500 --> 00:34:59,990 And so if you like to run, you can just meet there. 682 00:34:59,990 --> 00:35:03,560 We'll go on a run around the Charles. 683 00:35:03,560 --> 00:35:06,140 And this is not a competitive event. 684 00:35:06,140 --> 00:35:08,900 I'm not some fitness nut. 685 00:35:08,900 --> 00:35:13,610 I ran home last week, and I ate half a bag of Swedish fish 686 00:35:13,610 --> 00:35:14,630 on the way. 687 00:35:14,630 --> 00:35:17,000 So it's not a competition. 688 00:35:17,000 --> 00:35:19,430 It's just to try to get to know you guys 689 00:35:19,430 --> 00:35:24,123 and to try to break the ice in sort of a non-academic way. 690 00:35:24,123 --> 00:35:25,040 BARBARA IMPERIALI: OK. 691 00:35:25,040 --> 00:35:28,040 So I'm just going to wrap up here. 692 00:35:28,040 --> 00:35:30,590 So we bombed you with quite a lot of-- yes, over there. 693 00:35:30,590 --> 00:35:32,090 You want to know more about running. 694 00:35:32,090 --> 00:35:34,787 [INAUDIBLE] 695 00:35:34,787 --> 00:35:36,870 AUDIENCE: Will you still have normal office hours. 696 00:35:36,870 --> 00:35:39,850 PROFESSOR MARTIN: Yeah I'll have normal office hours. 697 00:35:39,850 --> 00:35:41,840 Yeah, or you could join me at CrossFit 698 00:35:41,840 --> 00:35:44,870 if you would like as well. 699 00:35:44,870 --> 00:35:47,870 We will both have office hours, and we will post them. 700 00:35:47,870 --> 00:35:50,840 And we welcome you to come visit us and, you know, 701 00:35:50,840 --> 00:35:53,760 find out more, tell us more about yourselves. 702 00:35:53,760 --> 00:35:56,990 We are fountains of information. 703 00:35:56,990 --> 00:36:00,660 So basically over the first half of the course, 704 00:36:00,660 --> 00:36:02,840 we tend to cover foundations. 705 00:36:02,840 --> 00:36:07,240 And so we build on biochemistry, one of my favorite subjects, 706 00:36:07,240 --> 00:36:09,840 where we cover all of the molecules of life. 707 00:36:09,840 --> 00:36:14,270 What are all the bits it takes to make a cell, lipids, sugars, 708 00:36:14,270 --> 00:36:16,310 proteins, nucleic acids. 709 00:36:16,310 --> 00:36:18,560 Then we synthesize them all together, 710 00:36:18,560 --> 00:36:21,650 where we show, in molecular biology, 711 00:36:21,650 --> 00:36:24,980 how the genome encodes the proteome, 712 00:36:24,980 --> 00:36:27,740 and what happens to the proteome after that. 713 00:36:27,740 --> 00:36:30,350 So you'll see me for all of those lectures. 714 00:36:30,350 --> 00:36:34,700 Then I will hand you over to Professor Martin for genetics, 715 00:36:34,700 --> 00:36:38,630 for the learning how to manipulate DNA. 716 00:36:38,630 --> 00:36:41,570 And we'll cap-off this first phase of work 717 00:36:41,570 --> 00:36:44,000 with cell signaling and understanding 718 00:36:44,000 --> 00:36:46,580 much more about dynamics of cells, 719 00:36:46,580 --> 00:36:49,010 as opposed to static building blocks. 720 00:36:49,010 --> 00:36:51,950 But you've got to understand the building blocks before you 721 00:36:51,950 --> 00:36:53,870 can understand the complexity. 722 00:36:53,870 --> 00:36:57,830 That's why I really like to cover those molecules 723 00:36:57,830 --> 00:36:59,030 at a reasonable depth. 724 00:36:59,030 --> 00:37:00,710 It's kind of ridiculous, 4 classes. 725 00:37:00,710 --> 00:37:02,970 But nevertheless, that's how we start. 726 00:37:02,970 --> 00:37:05,540 For some of you, you've seen some of it before. 727 00:37:05,540 --> 00:37:08,660 For others, you've seen none of it before. 728 00:37:08,660 --> 00:37:10,310 It doesn't matter. 729 00:37:10,310 --> 00:37:13,160 We will give you our flavor on it. 730 00:37:13,160 --> 00:37:15,110 If your chemistry is a little weak, 731 00:37:15,110 --> 00:37:17,640 I suggest you read the textbook. 732 00:37:17,640 --> 00:37:20,600 There's a couple of sections on just chemical covalent 733 00:37:20,600 --> 00:37:22,790 and non-covalent bonding, that you'll 734 00:37:22,790 --> 00:37:25,280 need to do the first P set. 735 00:37:25,280 --> 00:37:27,470 If your chemistry is strong, you're fine. 736 00:37:27,470 --> 00:37:29,900 If your chemistry is weak and you need a little help, 737 00:37:29,900 --> 00:37:31,700 I'll run an extra session next week. 738 00:37:31,700 --> 00:37:34,160 We can take care of every eventuality 739 00:37:34,160 --> 00:37:36,290 because you're a smaller class. 740 00:37:36,290 --> 00:37:39,390 And then we'll take it from there. 741 00:37:39,390 --> 00:37:41,300 And then what I really want to do 742 00:37:41,300 --> 00:37:44,490 is encourage you to do the reading. 743 00:37:44,490 --> 00:37:46,340 Make sure you're in a recitation. 744 00:37:46,340 --> 00:37:48,260 And next time, but it's in the sidebar, 745 00:37:48,260 --> 00:37:50,930 I'd like you to take a look at the sliding scale which 746 00:37:50,930 --> 00:37:54,710 shows you the dimensions of molecules, macromolecules, 747 00:37:54,710 --> 00:37:58,280 and organisms, which I find rather cool, even though it's 748 00:37:58,280 --> 00:38:00,090 probably built for high school students. 749 00:38:00,090 --> 00:38:00,590 OK. 750 00:38:00,590 --> 00:38:03,010 That's it from us for now.