WEBVTT 00:00:17.683 --> 00:00:18.600 BARBARA IMPERIALI: OK. 00:00:18.600 --> 00:00:19.642 We're going to get going. 00:00:19.642 --> 00:00:21.740 Now, we have a small class this year 00:00:21.740 --> 00:00:24.830 because of changes in the institute with pass/fail types 00:00:24.830 --> 00:00:29.360 of things, but Professor Martin and Dr. Ray 00:00:29.360 --> 00:00:33.020 and I consider this to be a special opportunity for us 00:00:33.020 --> 00:00:36.320 to run the course a little bit differently with a few more 00:00:36.320 --> 00:00:38.150 quirks and surprises. 00:00:38.150 --> 00:00:40.460 Because we have a small number of you, 00:00:40.460 --> 00:00:42.290 we can listen to you all. 00:00:42.290 --> 00:00:44.180 We can get input from you. 00:00:44.180 --> 00:00:46.490 We can even get feedback from you of something 00:00:46.490 --> 00:00:48.650 you might like to see more of. 00:00:48.650 --> 00:00:52.280 And in general, we really want to capture the sense of you. 00:00:52.280 --> 00:00:54.680 I have looked at the registration list. 00:00:54.680 --> 00:00:57.320 We have people from every year. 00:00:57.320 --> 00:01:01.130 We have people from many, many different disciplines. 00:01:01.130 --> 00:01:04.250 So this is what we're going to do today after we I start doing 00:01:04.250 --> 00:01:06.310 some introductions and so on. 00:01:06.310 --> 00:01:08.060 We're going to talk about the nitty gritty 00:01:08.060 --> 00:01:09.560 of the organization. 00:01:09.560 --> 00:01:10.820 We need to tell you this. 00:01:10.820 --> 00:01:13.190 We need to convey this information to you 00:01:13.190 --> 00:01:17.000 clearly about when exams are, and what requirements are, 00:01:17.000 --> 00:01:20.480 and how to do well in this course without even realizing 00:01:20.480 --> 00:01:21.980 it, that kind of thing. 00:01:21.980 --> 00:01:25.940 And then I'll take you through this sort of fast track 00:01:25.940 --> 00:01:28.520 through molecules to man, all the way down 00:01:28.520 --> 00:01:31.250 to cells and organisms, to show you 00:01:31.250 --> 00:01:36.260 that there was a breakpoint in the 1950s where 00:01:36.260 --> 00:01:40.970 the structure, the non-covalent structure of DNA 00:01:40.970 --> 00:01:42.620 was elucidated. 00:01:42.620 --> 00:01:44.420 And there was an entire revolution 00:01:44.420 --> 00:01:47.870 after that which makes modern biology, the study 00:01:47.870 --> 00:01:52.610 of modern biology, so entirely different from the study 00:01:52.610 --> 00:01:55.280 of biology in the era before that. 00:01:55.280 --> 00:01:58.940 Biology used to be considered taxonomy and dissection, 00:01:58.940 --> 00:02:01.950 like listing and looking at. 00:02:01.950 --> 00:02:06.200 But now biology, modern biology, is a molecular science. 00:02:06.200 --> 00:02:10.160 So as we talk about these topics, what you will see 00:02:10.160 --> 00:02:14.750 is the blueprints for life are common across domains of life. 00:02:14.750 --> 00:02:17.240 And if you learn basic principles, 00:02:17.240 --> 00:02:20.510 you'll have an exponential increase in your ability 00:02:20.510 --> 00:02:22.780 to appreciate these characteristics, 00:02:22.780 --> 00:02:26.940 that modern biology is a synthesis of science, 00:02:26.940 --> 00:02:30.500 technology, engineering, where all the tools from those 00:02:30.500 --> 00:02:33.560 disciplines, different disciplines-- physics, math, 00:02:33.560 --> 00:02:34.850 computation-- 00:02:34.850 --> 00:02:39.540 funnel into modern biology to make what we know now feasible, 00:02:39.540 --> 00:02:44.600 and that's a dramatic and fantastic opportunity for all 00:02:44.600 --> 00:02:47.180 of you moving forward in your careers. 00:02:47.180 --> 00:02:49.500 Now I want to introduce the team. 00:02:49.500 --> 00:02:51.110 So I'm Barbara Imperiali. 00:02:51.110 --> 00:02:54.140 I'm a faculty member in chemistry and biology, 00:02:54.140 --> 00:02:58.160 and I'm really interested in chemical biology, 00:02:58.160 --> 00:03:00.350 glycobiology, biophysics. 00:03:00.350 --> 00:03:04.520 I love to tease apart complex pathways in organisms 00:03:04.520 --> 00:03:09.530 where you biosynthesize very unusual glycol conjugate that 00:03:09.530 --> 00:03:13.130 are very important for cell-cell communication and host cell 00:03:13.130 --> 00:03:15.650 pathogen communication, for example. 00:03:15.650 --> 00:03:17.690 I was trained as an organic chemist. 00:03:17.690 --> 00:03:20.840 In fact, I did my PhD degree at MIT 00:03:20.840 --> 00:03:24.450 about five million years ago on a sort of current scale. 00:03:24.450 --> 00:03:30.410 So my co-instructor is professot-- 00:03:30.410 --> 00:03:32.721 sorry about this, but they want us on video. 00:03:41.108 --> 00:03:41.900 ADAM MARTIN: Hello. 00:03:41.900 --> 00:03:44.900 I'm Professor Martin, and my lab is 00:03:44.900 --> 00:03:49.130 interested in how cells generate mechanical forces 00:03:49.130 --> 00:03:51.830 and how this is involved in sculpting tissues 00:03:51.830 --> 00:03:52.850 during development. 00:03:55.388 --> 00:03:57.680 BARBARA IMPERIALI: So what Adam hasn't told you is he's 00:03:57.680 --> 00:04:00.230 a cell biologist, a biophysicist, 00:04:00.230 --> 00:04:03.650 and he's a lot better at genetics than I am. 00:04:03.650 --> 00:04:08.540 Our instructor is Dr. Diviya Ray who's been with this course, 00:04:08.540 --> 00:04:11.060 now this is the sixth year, and she 00:04:11.060 --> 00:04:14.990 is trained in immunology, cancer biology, and also 00:04:14.990 --> 00:04:16.820 cellular signaling. 00:04:16.820 --> 00:04:18.410 But what you can't tell from that 00:04:18.410 --> 00:04:22.010 is how dedicated she is to each and every one of you. 00:04:22.010 --> 00:04:26.420 If you have any trouble in the semester, just contact Dr. Ray 00:04:26.420 --> 00:04:30.590 and say, I need some help, be it a particular problem 00:04:30.590 --> 00:04:33.260 in the material, or there's just something come up 00:04:33.260 --> 00:04:37.100 that makes it difficult for you to do your best in the course. 00:04:37.100 --> 00:04:37.940 She will help you. 00:04:37.940 --> 00:04:41.930 She'll work out mechanisms to get you through troubled spots. 00:04:41.930 --> 00:04:44.020 So let's get going here. 00:04:44.020 --> 00:04:47.330 Now, what I want to try to do is just 00:04:47.330 --> 00:04:49.820 give you sort of a flavor of where we're 00:04:49.820 --> 00:04:54.380 going to within the course by starting with a few bullet 00:04:54.380 --> 00:04:57.230 points and topics just that I can sort of 00:04:57.230 --> 00:04:58.830 pique your interest. 00:04:58.830 --> 00:05:01.700 So as I mentioned before, studying biology 00:05:01.700 --> 00:05:05.930 in the 21st century is a fabulous opportunity. 00:05:05.930 --> 00:05:09.260 No matter what discipline you come from, 00:05:09.260 --> 00:05:14.480 you can add to the expertise that will move biology forward. 00:05:14.480 --> 00:05:17.150 Biology would not be where it is today 00:05:17.150 --> 00:05:21.140 in the absence of science, engineering to promote it 00:05:21.140 --> 00:05:23.660 and to support progress in biology. 00:05:23.660 --> 00:05:25.360 So you really want to realize that, 00:05:25.360 --> 00:05:27.470 that you have an opportunity. 00:05:27.470 --> 00:05:30.132 You may say, well, I'm in this discipline or other. 00:05:30.132 --> 00:05:32.090 I don't think biology is going to have anything 00:05:32.090 --> 00:05:36.140 to do with my future career or career opportunities. 00:05:36.140 --> 00:05:38.360 But it has a lot to do with your life. 00:05:38.360 --> 00:05:41.540 It has a lot to do with understanding health 00:05:41.540 --> 00:05:45.860 and disease, understanding new scientific discoveries 00:05:45.860 --> 00:05:47.060 and developments. 00:05:47.060 --> 00:05:50.660 So it's so important that you, as a scholar 00:05:50.660 --> 00:05:54.830 of the 21st century, have a good grasp on these materials. 00:05:54.830 --> 00:05:57.650 And we're not trying to feed you anything dull and boring. 00:05:57.650 --> 00:06:02.450 This is really exciting stuff, because the level of complexity 00:06:02.450 --> 00:06:04.520 that we can study nowadays-- 00:06:04.520 --> 00:06:08.240 whole genomes, whole organisms at a molecular level-- 00:06:08.240 --> 00:06:09.900 is amazing. 00:06:09.900 --> 00:06:10.670 It's amazing. 00:06:10.670 --> 00:06:12.560 We're not just peering down a slide 00:06:12.560 --> 00:06:15.350 and looking at one cell or something. 00:06:15.350 --> 00:06:18.110 We will be able to do full descriptions. 00:06:18.110 --> 00:06:22.820 So what we'll try to give you is a view 00:06:22.820 --> 00:06:24.590 of the fundamental principles that are 00:06:24.590 --> 00:06:27.150 common to all living organisms. 00:06:27.150 --> 00:06:29.330 So the study of biology, some people 00:06:29.330 --> 00:06:32.480 are microbiologists, or eukaryotic biologists, 00:06:32.480 --> 00:06:36.770 or human biologists, or they study virology. 00:06:36.770 --> 00:06:39.920 But we're going to build for you, in the first few weeks 00:06:39.920 --> 00:06:43.430 of class, information on the common building blocks 00:06:43.430 --> 00:06:46.610 that go across all domains of life. 00:06:46.610 --> 00:06:50.270 Because once you start to learn about those molecules, 00:06:50.270 --> 00:06:53.180 the build up, the macromolecules of life, 00:06:53.180 --> 00:06:57.170 then you'll start to really gain an understanding how amazing it 00:06:57.170 --> 00:07:00.140 is that these same sets of molecules 00:07:00.140 --> 00:07:03.680 function across from bacteria to man. 00:07:03.680 --> 00:07:07.315 So you learn the rules for the simplest organisms. 00:07:07.315 --> 00:07:08.690 You look at the molecules and you 00:07:08.690 --> 00:07:12.680 see how form fulfills function, which is something I'm really 00:07:12.680 --> 00:07:14.630 excited about, and then you'll be 00:07:14.630 --> 00:07:19.490 able to apply it as we get ever more complex systems which 00:07:19.490 --> 00:07:21.740 demand a lot of attention. 00:07:21.740 --> 00:07:25.400 So there's a common molecular logic 00:07:25.400 --> 00:07:27.790 of very complex processes. 00:07:27.790 --> 00:07:29.900 Motivations-- I just mentioned a few. 00:07:29.900 --> 00:07:33.680 Sure, you want to understand health and disease. 00:07:33.680 --> 00:07:36.380 You want to understand what might be going on 00:07:36.380 --> 00:07:38.180 with current therapies. 00:07:38.180 --> 00:07:41.510 When you have a relative who's been diagnosed 00:07:41.510 --> 00:07:45.140 with a serious disease, what are the current opportunities? 00:07:45.140 --> 00:07:46.130 What's coming down? 00:07:46.130 --> 00:07:49.820 What sorts of opportunities for therapy might be available? 00:07:49.820 --> 00:07:51.770 Because there are so many diseases now 00:07:51.770 --> 00:07:54.270 we understand at a molecular level. 00:07:54.270 --> 00:07:57.230 We may not understand how to treat them yet, 00:07:57.230 --> 00:08:00.110 but we understand what their origin is, 00:08:00.110 --> 00:08:05.000 and that's why molecular approaches are so important. 00:08:05.000 --> 00:08:07.550 You may often hear of words like systems 00:08:07.550 --> 00:08:09.980 biology and synthetic biology. 00:08:09.980 --> 00:08:13.520 These are kind of jazzy words for fairly straightforward 00:08:13.520 --> 00:08:14.090 things. 00:08:14.090 --> 00:08:16.880 Systems biology is a little bit like treating 00:08:16.880 --> 00:08:21.710 an organism or a cell as an electrical network, a wiring 00:08:21.710 --> 00:08:23.360 diagram. 00:08:23.360 --> 00:08:25.250 What proteins talk to what proteins? 00:08:25.250 --> 00:08:27.050 What are downstream functions? 00:08:27.050 --> 00:08:28.570 Where are signals amplified? 00:08:28.570 --> 00:08:29.070 And so on. 00:08:29.070 --> 00:08:31.760 So that's systems biology at its heart, 00:08:31.760 --> 00:08:34.130 quantifying different intermediates 00:08:34.130 --> 00:08:36.530 in a complex map of the cell. 00:08:36.530 --> 00:08:39.679 Synthetic biology is about using biology 00:08:39.679 --> 00:08:42.350 to make stuff, which is really cool. 00:08:42.350 --> 00:08:46.020 Many, many important molecules can be made in the lab, 00:08:46.020 --> 00:08:49.760 but it's so much more effective to make them in an organism. 00:08:49.760 --> 00:08:52.520 People are doing what they call synthetic biology, 00:08:52.520 --> 00:08:54.680 and that's exploiting and harnessing 00:08:54.680 --> 00:08:57.350 nature to make things that are useful for mankind. 00:09:00.740 --> 00:09:02.720 And all the way through, what I just 00:09:02.720 --> 00:09:05.930 want to emphasize how integrating technology 00:09:05.930 --> 00:09:09.020 and engineering for science is really 00:09:09.020 --> 00:09:10.640 what we're all about here, because we 00:09:10.640 --> 00:09:13.400 appreciate we couldn't make the progress without it. 00:09:13.400 --> 00:09:17.120 There are also issues general biology impacts 00:09:17.120 --> 00:09:20.840 that are in the social sciences and impinge 00:09:20.840 --> 00:09:24.230 on things like ethics, designer babies, 00:09:24.230 --> 00:09:28.550 cloning people, cloning your pets, all kinds of things, 00:09:28.550 --> 00:09:35.020 treating a disease through genetics or not, [INAUDIBLE] 00:09:35.020 --> 00:09:36.950 some of these new innovations. 00:09:36.950 --> 00:09:38.780 But you really need to understand 00:09:38.780 --> 00:09:41.120 ethical issues related to them to be 00:09:41.120 --> 00:09:44.450 able to explain to your parents, or your grandparents, 00:09:44.450 --> 00:09:47.900 or your sister or brother who hasn't taken biology, what 00:09:47.900 --> 00:09:50.510 the implications of some of the things 00:09:50.510 --> 00:09:53.430 that we can do in biology, but probably we 00:09:53.430 --> 00:09:55.530 shouldn't do in biology. 00:09:55.530 --> 00:09:58.220 And we will welcome your thoughts on some of that 00:09:58.220 --> 00:09:59.700 later on. 00:09:59.700 --> 00:10:00.230 OK. 00:10:00.230 --> 00:10:03.110 So where did the world start? 00:10:03.110 --> 00:10:05.330 Arguably four and a half billion years ago 00:10:05.330 --> 00:10:07.250 is kind of a vague theme, but it started 00:10:07.250 --> 00:10:10.190 with the world, the earth, being a ball of fire, 00:10:10.190 --> 00:10:12.740 and it took quite a while for it to cool down 00:10:12.740 --> 00:10:18.140 to establish the hydrosphere and the globe as it's known today. 00:10:18.140 --> 00:10:21.620 There was a period of time known as the prebiotic world, where 00:10:21.620 --> 00:10:24.890 there were not living organisms that replicated, 00:10:24.890 --> 00:10:29.450 and that was basically a world where building blocks started 00:10:29.450 --> 00:10:33.110 to evolve out of fiery hot mud pits 00:10:33.110 --> 00:10:36.380 and in volcanoes and goodness knows where. 00:10:36.380 --> 00:10:38.510 People believe that the building blocks 00:10:38.510 --> 00:10:41.540 of life, just the molecules, came together 00:10:41.540 --> 00:10:44.300 from things like hydrogen cyanide, or sulfide, 00:10:44.300 --> 00:10:47.060 or other primordial components that 00:10:47.060 --> 00:10:49.400 were in the primordial soup. 00:10:49.400 --> 00:10:55.190 There was a phase known as the pre-RNA world, where the RNA 00:10:55.190 --> 00:10:56.600 building blocks were around. 00:10:56.600 --> 00:11:00.890 There's reasonable arguments in favor of the RNA world, 00:11:00.890 --> 00:11:03.080 where a lot of functions were catalyzed 00:11:03.080 --> 00:11:06.290 not by proteins, but by nucleic acids, specifically 00:11:06.290 --> 00:11:08.460 ribonucleic acids. 00:11:08.460 --> 00:11:14.870 So it's a period of time still pre-biotic 00:11:14.870 --> 00:11:19.160 that had the first pre-RNA, and then RNA world. 00:11:19.160 --> 00:11:21.800 But then things really started to get interesting 00:11:21.800 --> 00:11:24.710 when the first cells evolved. 00:11:24.710 --> 00:11:29.270 Now, I will talk a little bit about this in the next class, 00:11:29.270 --> 00:11:31.580 because the thing that's critical to be 00:11:31.580 --> 00:11:35.690 able to build a cell is to be able to build a wall around it. 00:11:35.690 --> 00:11:41.090 So very, very early on in life lipid bilayers, membranes, 00:11:41.090 --> 00:11:45.770 evolved in order to make compartmentalized structures 00:11:45.770 --> 00:11:48.890 where you could differentiate the in from the out. 00:11:48.890 --> 00:11:52.970 And so much of life is completely reliant on the fact 00:11:52.970 --> 00:11:54.200 that we're made of cells. 00:11:54.200 --> 00:11:58.100 We're not just one big sort of bucket of water with things 00:11:58.100 --> 00:11:59.330 floating around in it. 00:11:59.330 --> 00:12:02.660 Because so much of function becomes coordinated 00:12:02.660 --> 00:12:05.930 by cellular compartmentalization through things 00:12:05.930 --> 00:12:10.070 known as lipid bilayers, which are semi-permeable membranes. 00:12:10.070 --> 00:12:11.870 Oxygen can move across. 00:12:11.870 --> 00:12:14.810 Some small hydrophobic things can move across. 00:12:14.810 --> 00:12:18.050 But a lot of things get either stuck in or stuck out. 00:12:18.050 --> 00:12:19.800 So we'll talk a lot about that. 00:12:19.800 --> 00:12:22.820 So the first prokaryotes were cyanobacteria. 00:12:22.820 --> 00:12:24.980 They're photosynthetic bacteria. 00:12:24.980 --> 00:12:30.200 It was quite a long time until those unicellular organisms 00:12:30.200 --> 00:12:33.680 that totally lacked a nucleus, lacked a lot of intracellular 00:12:33.680 --> 00:12:37.580 compartmentalization, evolved to eukaryotes, 00:12:37.580 --> 00:12:39.630 and those cells are different. 00:12:39.630 --> 00:12:42.890 They're 100 or 1,000 times bigger. 00:12:42.890 --> 00:12:43.970 They're complex. 00:12:43.970 --> 00:12:45.710 They're compartmentalized. 00:12:45.710 --> 00:12:47.600 They can do a lot of functions. 00:12:47.600 --> 00:12:51.710 In a full organism they're very differentiated, 00:12:51.710 --> 00:12:55.070 and they may look different in muscle, or in heart, 00:12:55.070 --> 00:12:57.120 or in skin, or in bone. 00:12:57.120 --> 00:13:01.020 And so those eukaryotes-- so that's a long gap of time, 00:13:01.020 --> 00:13:03.440 but there was a lot going on in that phase. 00:13:03.440 --> 00:13:06.620 And about a half a billion years ago, multicellular life 00:13:06.620 --> 00:13:07.550 evolved. 00:13:07.550 --> 00:13:10.250 And multicellular life now can be looked at, 00:13:10.250 --> 00:13:13.070 if we think of the evolution of homo sapiens, 00:13:13.070 --> 00:13:17.000 can be thought of as something that we can keep track of a bit 00:13:17.000 --> 00:13:21.260 through fossil records over the last five million years, 00:13:21.260 --> 00:13:23.900 where the first humanoid life evolved. 00:13:23.900 --> 00:13:25.520 Then you got sort of to a stage-- 00:13:25.520 --> 00:13:29.750 I think he's homo ergaster, that this sort of Shrek-like person 00:13:29.750 --> 00:13:31.680 evolved quite early on. 00:13:31.680 --> 00:13:37.400 And then the humanoids gradually became different, evolved. 00:13:37.400 --> 00:13:39.710 In some cases there were branches of the tree 00:13:39.710 --> 00:13:41.750 of evolution and dead ends. 00:13:41.750 --> 00:13:44.060 In other places there was a branch 00:13:44.060 --> 00:13:45.410 that carried on for a while. 00:13:45.410 --> 00:13:49.160 For example, the neanderthal and homo sapiens kind of 00:13:49.160 --> 00:13:51.170 kept on evolving for a while. 00:13:51.170 --> 00:13:52.820 But there's a lot of developments 00:13:52.820 --> 00:13:55.730 that have been characterized from the fossil record. 00:13:55.730 --> 00:13:59.360 But now there's a lot of belief that if we trace things back 00:13:59.360 --> 00:14:03.170 through genomes, we might get more precise information 00:14:03.170 --> 00:14:05.310 on steps in evolution. 00:14:05.310 --> 00:14:09.620 Now, the evolution of the advanced, if you will, 00:14:09.620 --> 00:14:13.170 hominids really came along with a number of things. 00:14:13.170 --> 00:14:17.150 There was a stage at which a particular gene, the FOXP gene, 00:14:17.150 --> 00:14:21.400 is attributed to the ability for complex speech. 00:14:21.400 --> 00:14:24.320 And that could have been a leap forward when humanoids 00:14:24.320 --> 00:14:26.510 could communicate more, and it seems 00:14:26.510 --> 00:14:28.520 to be associated with that. 00:14:28.520 --> 00:14:31.250 But there are other sort of sociological functions, 00:14:31.250 --> 00:14:34.160 like burying the dead, or making jewelry, 00:14:34.160 --> 00:14:37.670 or making tools, that are associated with the more 00:14:37.670 --> 00:14:39.350 evolved organisms. 00:14:39.350 --> 00:14:43.580 There are other types of things like cranial capacity, standing 00:14:43.580 --> 00:14:45.380 upright, looking forward. 00:14:45.380 --> 00:14:50.000 A lot of things came through those years of the evolution 00:14:50.000 --> 00:14:51.960 of homo sapiens. 00:14:51.960 --> 00:14:54.410 So it's fascinating to think about that 00:14:54.410 --> 00:14:58.490 and to think what light genetics can shed on those five 00:14:58.490 --> 00:15:01.280 million years of evolution. 00:15:01.280 --> 00:15:06.710 Now, the world of biology took a mega kick start 00:15:06.710 --> 00:15:10.050 with the elucidation of the human genome, 00:15:10.050 --> 00:15:12.140 but more importantly of the technology 00:15:12.140 --> 00:15:17.820 necessary to solve the map of the whole human genome. 00:15:17.820 --> 00:15:21.030 In 2001 there was a major development 00:15:21.030 --> 00:15:24.450 with the publication of the first map of the human genome. 00:15:24.450 --> 00:15:27.540 It's fascinating to think with humans, 00:15:27.540 --> 00:15:31.680 we humans have about three billion genes, 00:15:31.680 --> 00:15:34.070 but there's only across human-- 00:15:34.070 --> 00:15:34.680 is that right? 00:15:34.680 --> 00:15:35.460 No, sorry. 00:15:35.460 --> 00:15:36.780 Base pairs, yes. 00:15:36.780 --> 00:15:38.190 Thank you very much. 00:15:38.190 --> 00:15:42.420 But across humankind there's enormous diversity, 00:15:42.420 --> 00:15:49.420 but that's accounted for by only about 0.1% of the diversity. 00:15:49.420 --> 00:15:52.450 So you can see people look very, very different, 00:15:52.450 --> 00:15:57.210 but we still share 99.9% of our genome. 00:15:57.210 --> 00:16:00.660 Another very interesting thing is that genomes vary in size 00:16:00.660 --> 00:16:03.413 quite considerably. 00:16:03.413 --> 00:16:04.830 Before I move forward, I just want 00:16:04.830 --> 00:16:07.320 to quickly show you this map. 00:16:07.320 --> 00:16:15.120 I mentioned tracing evolution through a molecular clock, 00:16:15.120 --> 00:16:19.230 so looking back in time not by following the shape of a skull, 00:16:19.230 --> 00:16:22.020 for example, or physiologic changes, 00:16:22.020 --> 00:16:26.340 but looking at genomes using the genome as a molecular clock 00:16:26.340 --> 00:16:30.090 based on mutation rates that are fairly constant amongst domains 00:16:30.090 --> 00:16:30.750 of life. 00:16:30.750 --> 00:16:33.570 You couldn't compare a human and a bacterium, 00:16:33.570 --> 00:16:37.050 but you can go back through a lot of eukaryotic evolution 00:16:37.050 --> 00:16:39.340 and see where divergence has happened. 00:16:39.340 --> 00:16:44.280 So in this map, you can see that human and neanderthal diverged 00:16:44.280 --> 00:16:47.010 from the chimpanzee a certain time ago, 00:16:47.010 --> 00:16:50.430 which had diverged from the gorilla further ago based 00:16:50.430 --> 00:16:53.650 on the molecular clock that's available. 00:16:53.650 --> 00:16:54.390 OK. 00:16:54.390 --> 00:16:56.550 So now I want to talk a little bit more 00:16:56.550 --> 00:16:59.460 about getting into the details of the genome. 00:16:59.460 --> 00:17:02.610 So genomes differ greatly in size. 00:17:02.610 --> 00:17:06.450 Our genome includes about three billion base pairs 00:17:06.450 --> 00:17:10.589 in our 22 chromosomes plus the X and Y chromosome, 00:17:10.589 --> 00:17:13.530 but the typical genome of a model bacterium 00:17:13.530 --> 00:17:16.150 has only five million base pairs. 00:17:16.150 --> 00:17:19.240 So far, far smaller, more tangible, 00:17:19.240 --> 00:17:21.900 more easy to study, because those genes 00:17:21.900 --> 00:17:25.560 are more limited in size, but the genome size 00:17:25.560 --> 00:17:28.500 is not necessarily proportionate to the number 00:17:28.500 --> 00:17:31.890 of genes that are expressed and made into proteins. 00:17:31.890 --> 00:17:37.830 A fascinating discovery is that of the three billion base 00:17:37.830 --> 00:17:43.950 pairs, only about 1.5% to 2% actually code for proteins, 00:17:43.950 --> 00:17:45.920 and there's a ton of interest now 00:17:45.920 --> 00:17:49.320 in what's the rest of the genome doing there. 00:17:49.320 --> 00:17:50.530 Where did it come from? 00:17:50.530 --> 00:17:51.663 What's its function? 00:17:51.663 --> 00:17:53.580 There are different functions that Eric Lander 00:17:53.580 --> 00:17:56.910 calls the dark matter of the genome, different functions 00:17:56.910 --> 00:17:58.650 to the rest of the genome. 00:17:58.650 --> 00:18:01.050 But the part that we focus on is the part 00:18:01.050 --> 00:18:03.870 that gets encoded into proteins that 00:18:03.870 --> 00:18:06.250 form the functions of the molecules of life. 00:18:06.250 --> 00:18:08.650 So we're going to focus ourselves in on those. 00:18:08.650 --> 00:18:12.240 But here you see differences in sizes of genomes 00:18:12.240 --> 00:18:13.930 based on base pair. 00:18:13.930 --> 00:18:17.490 But what's fascinating is despite this huge breadth 00:18:17.490 --> 00:18:21.960 of sizes and huge differences in organisms, 00:18:21.960 --> 00:18:23.610 the building blocks are the same. 00:18:23.610 --> 00:18:27.570 And that's what I think is the wonderful part of what we're 00:18:27.570 --> 00:18:32.610 able to teach you is, we can take you from the 1950s 00:18:32.610 --> 00:18:37.170 when the structure of double stranded DNA was first solved. 00:18:37.170 --> 00:18:39.810 Now, there were 60, 70, or more years of work 00:18:39.810 --> 00:18:42.630 before that where they figured out the pieces, 00:18:42.630 --> 00:18:45.090 they figured out the chemistry, the covalent bonds, 00:18:45.090 --> 00:18:48.120 and the bases, and the sugars, and the phosphodiester. 00:18:48.120 --> 00:18:54.240 But they had no clue how the DNA could encode and program 00:18:54.240 --> 00:18:56.310 the synthesis of a protein. 00:18:56.310 --> 00:19:01.380 But once the structure, the three-dimensional structure 00:19:01.380 --> 00:19:03.840 of double-stranded DNA was solved-- 00:19:03.840 --> 00:19:06.630 this is this beautiful anti-parallel structure that 00:19:06.630 --> 00:19:07.800 you see here-- 00:19:07.800 --> 00:19:11.070 by Watson, Crick, and Rosalind Franklin, 00:19:11.070 --> 00:19:14.198 then the clues came pouring in. 00:19:14.198 --> 00:19:16.740 Without that structure, without the structure of what's known 00:19:16.740 --> 00:19:20.250 as the non-covalent structure-- not the covalent structure, 00:19:20.250 --> 00:19:22.000 you'll see all those building blocks-- 00:19:22.000 --> 00:19:23.580 but the non-covalent structure, how 00:19:23.580 --> 00:19:27.000 you could zipper apart the two strands of DNA 00:19:27.000 --> 00:19:30.480 and make copies of both of them and replicate DNA and then 00:19:30.480 --> 00:19:31.450 go forward. 00:19:31.450 --> 00:19:33.750 That was an amazing step forward, 00:19:33.750 --> 00:19:36.360 and for that, there was a Nobel Prize awarded. 00:19:36.360 --> 00:19:38.550 Unfortunately it was after Franklin's death. 00:19:38.550 --> 00:19:44.260 So it was given to Watson and Crick and a third person. 00:19:44.260 --> 00:19:46.780 Now, here's has that structure of DNA. 00:19:46.780 --> 00:19:49.960 I could sort of watch it for hours to be honest. 00:19:49.960 --> 00:19:53.620 The phosphodiester background-- backbone going up the back, 00:19:53.620 --> 00:19:56.130 and the bases base pairing across. 00:19:56.130 --> 00:19:59.290 And these are the key steps that happened from the '50s. 00:19:59.290 --> 00:20:01.900 So in the definite-- after the definition 00:20:01.900 --> 00:20:06.140 of the double stranded structure, it took a few years, 00:20:06.140 --> 00:20:09.290 but they cracked what's known as the genetic code. 00:20:09.290 --> 00:20:13.930 How does that DNA get converted into a protein? 00:20:13.930 --> 00:20:17.260 What happens is you make an RNA copy of the DNA. 00:20:17.260 --> 00:20:20.110 And the RNA is read to make a protein. 00:20:20.110 --> 00:20:22.600 And you will learn about all those components. 00:20:22.600 --> 00:20:25.060 But that was another real landmark. 00:20:25.060 --> 00:20:28.240 Then what was really exciting is that some technology 00:20:28.240 --> 00:20:31.390 companies started figuring out, first, there 00:20:31.390 --> 00:20:34.750 were very slow ways to sequence DNA. 00:20:34.750 --> 00:20:38.560 But in the-- and that happened in 1977. 00:20:38.560 --> 00:20:41.950 But what was really important is about a decade later, 00:20:41.950 --> 00:20:44.140 where the ability to sequence DNA 00:20:44.140 --> 00:20:47.680 was not done anymore using huge agarose gels 00:20:47.680 --> 00:20:49.570 and a bucket of radioactivity. 00:20:49.570 --> 00:20:52.090 But it was done through using fluorescence, 00:20:52.090 --> 00:20:56.560 in order to allow you to read out the sequence of DNA. 00:20:56.560 --> 00:20:58.750 And you will learn about that. 00:20:58.750 --> 00:21:01.900 And in 1987, the instruments were 00:21:01.900 --> 00:21:05.770 commercialized, major, major technology and engineering. 00:21:05.770 --> 00:21:08.110 We wouldn't be anywhere without that. 00:21:08.110 --> 00:21:11.620 In 1990, the Human Genome Project began. 00:21:11.620 --> 00:21:16.300 In '01, the draft of the human genome sequence was completed. 00:21:16.300 --> 00:21:18.940 2010, you could sequence a single strand 00:21:18.940 --> 00:21:21.940 of DNA, one molecule of DNA. 00:21:21.940 --> 00:21:23.530 And now there's so many initiatives 00:21:23.530 --> 00:21:24.680 that have come out of that. 00:21:24.680 --> 00:21:27.550 And so much amazing technology that has evolved. 00:21:27.550 --> 00:21:30.760 So things like the 1,000 Genomes Project 00:21:30.760 --> 00:21:34.757 to look at variation across man, so all people 00:21:34.757 --> 00:21:36.340 from all different parts of the world. 00:21:36.340 --> 00:21:37.660 You can look up that website. 00:21:37.660 --> 00:21:39.760 That's very cool. 00:21:39.760 --> 00:21:42.310 The Human Cell Atlas, there was quite a bit of news 00:21:42.310 --> 00:21:45.460 about that in MIT Technology News, 00:21:45.460 --> 00:21:49.420 where Aviv Regev is playing a major part in that, 00:21:49.420 --> 00:21:52.210 to actually sequence representatives 00:21:52.210 --> 00:21:58.210 from all of your trillions of cells and see how they differ. 00:21:58.210 --> 00:22:02.710 And then there's cancer genome projects and precision medicine 00:22:02.710 --> 00:22:05.710 sequence every type of cancer cell, 00:22:05.710 --> 00:22:07.540 find out what's different about it, 00:22:07.540 --> 00:22:09.940 and precisely figure out how to treat 00:22:09.940 --> 00:22:12.130 it, all very exciting things. 00:22:12.130 --> 00:22:14.620 And then of course, there's synthetic genomes, where 00:22:14.620 --> 00:22:17.410 you can literally build a cell and its genome, 00:22:17.410 --> 00:22:20.163 program it to do what you want, hopefully. 00:22:20.163 --> 00:22:21.580 And then there's one of the things 00:22:21.580 --> 00:22:23.413 that your generation will have to deal with, 00:22:23.413 --> 00:22:24.640 and that's all the data. 00:22:24.640 --> 00:22:27.640 Because we've just found ways to churn it out. 00:22:27.640 --> 00:22:30.730 But you guys are going to have to do the heavy lifting there. 00:22:30.730 --> 00:22:34.720 So DNA, then, looking at that structure, 00:22:34.720 --> 00:22:37.150 is packaged into cells. 00:22:37.150 --> 00:22:39.340 So figure this one out. 00:22:39.340 --> 00:22:44.740 Each human cell has 1.8 meters of DNA in it, 00:22:44.740 --> 00:22:49.900 yet it fits into a cell that's 10 to 100 microns in diameter. 00:22:49.900 --> 00:22:52.090 And it's bundled tightly up. 00:22:52.090 --> 00:22:56.500 So you'll learn how DNA in cells gets bundled up and wrapped 00:22:56.500 --> 00:23:00.100 around proteins that neutralize the negative charges 00:23:00.100 --> 00:23:03.970 of the double stranded DNA with positively charged proteins 00:23:03.970 --> 00:23:05.470 and enable packaging. 00:23:05.470 --> 00:23:07.690 So we will talk about all of this. 00:23:07.690 --> 00:23:09.640 When is DNA unraveled? 00:23:09.640 --> 00:23:11.860 What signals its unraveling? 00:23:11.860 --> 00:23:15.130 Because in order to copy it, you've got to unpack it. 00:23:15.130 --> 00:23:18.310 So these are a lot of details about DNA 00:23:18.310 --> 00:23:21.040 that you'll be able to sort of have much more sense of as we 00:23:21.040 --> 00:23:23.620 move forward. 00:23:23.620 --> 00:23:25.870 Cells are different in size. 00:23:25.870 --> 00:23:30.070 I just mentioned to you a typical eukaryotic cell 00:23:30.070 --> 00:23:34.840 is about 10 to 100 microns in diameter. 00:23:34.840 --> 00:23:38.950 A typical bacterial cell is about 1 to 10 microns. 00:23:38.950 --> 00:23:41.380 So there is a vast difference in sizes 00:23:41.380 --> 00:23:44.860 for these simple cells that have no nucleus, 00:23:44.860 --> 00:23:48.580 relative to the cells that are compartmentalized 00:23:48.580 --> 00:23:50.470 and perform a lot of functions. 00:23:50.470 --> 00:23:54.190 So we will learn to appreciate that difference in size, 00:23:54.190 --> 00:23:57.010 looking at the building blocks that go into all of them, 00:23:57.010 --> 00:24:00.700 but then understanding how big cells have 00:24:00.700 --> 00:24:04.210 to have a lot more complexity in their signaling 00:24:04.210 --> 00:24:06.580 in order to establish their functions 00:24:06.580 --> 00:24:09.970 but also interact with other cells in multicellular 00:24:09.970 --> 00:24:11.920 organisms. 00:24:11.920 --> 00:24:14.380 We're still doing fine for time, yes. 00:24:14.380 --> 00:24:17.500 The other thing that we will spend several classes on 00:24:17.500 --> 00:24:21.820 is imaging and visualization of things going on in cells. 00:24:21.820 --> 00:24:24.640 So what we'll talk to you about is the discovery 00:24:24.640 --> 00:24:27.670 of fluorescent proteins, which have provided 00:24:27.670 --> 00:24:31.150 an unparalleled opportunity to label proteins 00:24:31.150 --> 00:24:35.050 within living organisms in order to track what they do. 00:24:35.050 --> 00:24:37.630 And through the efforts of protein engineers, 00:24:37.630 --> 00:24:41.050 there is an entire panel of colored proteins that 00:24:41.050 --> 00:24:42.610 fluoresce at different wavelengths 00:24:42.610 --> 00:24:48.910 that we can use to study biology in live systems, in real time. 00:24:48.910 --> 00:24:51.180 These slides show you a little bit of that. 00:24:51.180 --> 00:24:54.600 I love these pictures, just showing a dividing cell. 00:24:54.600 --> 00:24:58.080 Where the chromosomes you see red because the histones 00:24:58.080 --> 00:25:00.420 are labeled with red fluorescent protein, 00:25:00.420 --> 00:25:04.260 and all that green fuzzy stuff are microtubules around. 00:25:04.260 --> 00:25:05.250 We can do this now. 00:25:05.250 --> 00:25:09.960 You couldn't do this 15 years ago, observe these changes. 00:25:09.960 --> 00:25:13.110 We can also look at changes as cells divide and go 00:25:13.110 --> 00:25:14.610 through the cell cycle. 00:25:14.610 --> 00:25:17.470 One of my favorites is this where 00:25:17.470 --> 00:25:21.420 of going through the stages to program a cell to divide, 00:25:21.420 --> 00:25:24.390 a new protein gets made, and then it settles down. 00:25:24.390 --> 00:25:28.170 But then when you go to divide again, you keep making-- 00:25:28.170 --> 00:25:32.160 you cyclically make different sets of proteins. 00:25:32.160 --> 00:25:36.060 And you can observe them in real time dividing. 00:25:36.060 --> 00:25:38.790 So just think if you were trying to make a chemotherapeutic 00:25:38.790 --> 00:25:40.980 where you wanted to stop cell division, 00:25:40.980 --> 00:25:43.830 or you wanted to inhibit one of those proteins, 00:25:43.830 --> 00:25:46.170 you could literally watch it function. 00:25:46.170 --> 00:25:47.490 Does it get in to cell? 00:25:47.490 --> 00:25:50.980 Does it disrupt the normal pattern of cell division? 00:25:50.980 --> 00:25:55.713 So these are capabilities that are now, really are available. 00:25:55.713 --> 00:25:57.130 So I've talked to you about cells. 00:25:57.130 --> 00:26:00.210 But I'm going to pass you over to Professor Martin 00:26:00.210 --> 00:26:03.255 for a little bit-- you'll get a little bit of a sense of how 00:26:03.255 --> 00:26:03.840 he thinks. 00:26:07.580 --> 00:26:10.480 And then I'll do the wrap up. 00:26:10.480 --> 00:26:12.170 PROFESSOR MARTIN: Thank you. 00:26:12.170 --> 00:26:16.340 So this is one of my favorite model organisms. 00:26:16.340 --> 00:26:22.270 This is a fruit fly, at larger than real size. 00:26:22.270 --> 00:26:27.970 And so one topic that I'll start on when 00:26:27.970 --> 00:26:32.140 I start lecturing either at the end of this month 00:26:32.140 --> 00:26:36.040 or beginning of October is we'll talk a lot about genetics. 00:26:36.040 --> 00:26:39.640 And one thing we'll start on is pioneering research 00:26:39.640 --> 00:26:43.900 done in this system to establish the chromosome 00:26:43.900 --> 00:26:45.790 theory of inheritance. 00:26:45.790 --> 00:26:46.740 OK. 00:26:46.740 --> 00:26:50.140 And we'll talk about the importance in model organisms 00:26:50.140 --> 00:26:52.900 in discovering new biology. 00:26:52.900 --> 00:26:55.150 But in addition to that, I also want 00:26:55.150 --> 00:27:00.280 to talk about how genetics will affect you guys as you go on 00:27:00.280 --> 00:27:05.020 and graduate from MIT and go into your own careers. 00:27:05.020 --> 00:27:08.440 Because genetics is really playing an important role 00:27:08.440 --> 00:27:10.270 in all our lives. 00:27:10.270 --> 00:27:14.170 And already, you guys have the option 00:27:14.170 --> 00:27:17.310 to get your DNA genotyped, right. 00:27:17.310 --> 00:27:23.140 There are lots of companies now like 23andMe and Ancestry.com 00:27:23.140 --> 00:27:25.270 where you can get your DNA genotyped. 00:27:25.270 --> 00:27:28.660 And you can learn about your ancestry. 00:27:28.660 --> 00:27:32.050 You can learn about whether you might be predisposed 00:27:32.050 --> 00:27:34.790 towards certain diseases. 00:27:34.790 --> 00:27:40.480 And so in order to appreciate the data you get back 00:27:40.480 --> 00:27:43.240 from these companies, you really have to understand something 00:27:43.240 --> 00:27:44.740 about genetics. 00:27:44.740 --> 00:27:47.250 And another thing which I find very fascinating 00:27:47.250 --> 00:27:51.860 are ethical issues that come up with the use of such sites. 00:27:51.860 --> 00:27:56.890 And you might have seen this in the news last semester. 00:27:56.890 --> 00:28:01.330 Both forensic experts and police identified 00:28:01.330 --> 00:28:05.410 a suspect in a killing that happened 40 years ago. 00:28:05.410 --> 00:28:11.650 And this was in part due to using the suspect's family 00:28:11.650 --> 00:28:12.430 tree. 00:28:12.430 --> 00:28:13.690 OK. 00:28:13.690 --> 00:28:16.760 And so they used the family tree, you know, some-- 00:28:16.760 --> 00:28:19.720 you know, this guy's relatives had done one of these 00:28:19.720 --> 00:28:20.350 Ancestry.com's. 00:28:20.350 --> 00:28:25.810 And they used the information from DNA 00:28:25.810 --> 00:28:28.330 acquired from other individuals to track down 00:28:28.330 --> 00:28:30.130 this other individual. 00:28:30.130 --> 00:28:32.150 OK. 00:28:32.150 --> 00:28:35.030 So one thing that I find incredibly exciting 00:28:35.030 --> 00:28:39.260 about biology is that it is truly dynamic. 00:28:39.260 --> 00:28:40.160 OK. 00:28:40.160 --> 00:28:42.260 And this is a human neutrophil. 00:28:42.260 --> 00:28:44.700 And it's just a bright field microscopy. 00:28:44.700 --> 00:28:46.370 Nothing's labeled. 00:28:46.370 --> 00:28:49.660 And what you're seeing here is this-- 00:28:49.660 --> 00:28:52.930 this neutrophil is chasing after this bacterium. 00:28:52.930 --> 00:28:55.600 And it illustrates another concept 00:28:55.600 --> 00:28:59.290 that we'll talk about in this course, which is signaling. 00:28:59.290 --> 00:29:02.440 So this neutrophil is receiving a signal 00:29:02.440 --> 00:29:05.800 from this bacteria that tells it where it is. 00:29:05.800 --> 00:29:10.230 And it's then able to chase that bacterium and track it down. 00:29:10.230 --> 00:29:12.870 And there you see it just got the bacterium. 00:29:12.870 --> 00:29:13.990 OK. 00:29:13.990 --> 00:29:19.000 So we'll talk about dynamic processes that cells do 00:29:19.000 --> 00:29:23.200 and how that's important for their function. 00:29:23.200 --> 00:29:25.880 In addition to considering single cells, 00:29:25.880 --> 00:29:28.660 we also want to understand how entire organisms 00:29:28.660 --> 00:29:30.370 and tissues work. 00:29:30.370 --> 00:29:32.950 And I want to emphasize that, yes, 00:29:32.950 --> 00:29:36.700 we have sequence-- or researchers have sequenced 00:29:36.700 --> 00:29:41.080 the human genome and the genomes of many different organisms, 00:29:41.080 --> 00:29:41.890 OK. 00:29:41.890 --> 00:29:43.210 And that's great, right. 00:29:43.210 --> 00:29:45.790 We have this data set. 00:29:45.790 --> 00:29:50.080 But we still don't understand how all the components that 00:29:50.080 --> 00:29:52.900 are in the genome are wired together 00:29:52.900 --> 00:29:56.500 and work in order to create a complicated organism 00:29:56.500 --> 00:29:57.900 like ourselves. 00:29:57.900 --> 00:29:58.720 OK. 00:29:58.720 --> 00:30:01.660 And so one aspect of that, which is mysterious, 00:30:01.660 --> 00:30:04.890 is how does the genome encode shape? 00:30:04.890 --> 00:30:05.590 OK. 00:30:05.590 --> 00:30:07.900 How do we get our shape, and how do we 00:30:07.900 --> 00:30:09.980 get the shape of our organs? 00:30:09.980 --> 00:30:12.940 And this is something that my lab is interested in. 00:30:12.940 --> 00:30:17.400 And so this is a fruit fly embryo. 00:30:17.400 --> 00:30:19.830 And you can see at the beginning here, 00:30:19.830 --> 00:30:22.260 this is three hours into development. 00:30:22.260 --> 00:30:26.190 You just have a smooth surface for this embryo. 00:30:26.190 --> 00:30:29.760 But during development, this changes. 00:30:29.760 --> 00:30:32.520 And I'm just showing you here a cross-section 00:30:32.520 --> 00:30:33.470 of the same embryo. 00:30:33.470 --> 00:30:35.130 And you see, it's a sheet of cells 00:30:35.130 --> 00:30:37.480 that surrounds a central yolk. 00:30:37.480 --> 00:30:37.980 OK. 00:30:37.980 --> 00:30:41.070 And this changes three hours into development, 00:30:41.070 --> 00:30:47.570 because a population of about 1,000 cells in this organism 00:30:47.570 --> 00:30:49.260 fold to form a crease. 00:30:49.260 --> 00:30:49.760 OK. 00:30:49.760 --> 00:30:52.490 So this is a dramatic shape change for this embryo. 00:30:52.490 --> 00:30:54.740 It goes from being a single layer 00:30:54.740 --> 00:30:56.910 to now having multiple layers. 00:30:56.910 --> 00:30:59.810 So this is a time course here, showing you 00:30:59.810 --> 00:31:02.630 how cells change shape in this tissue 00:31:02.630 --> 00:31:05.030 and how this leads to what's initially 00:31:05.030 --> 00:31:09.440 a single layer of cells to become two layers of cells. 00:31:09.440 --> 00:31:13.820 And this process is similar to morphogenetic events 00:31:13.820 --> 00:31:16.160 that happen in human embryos. 00:31:16.160 --> 00:31:21.350 But we can study this in fruit fly embryos or many other model 00:31:21.350 --> 00:31:25.430 systems, in order to try to understand mechanistically 00:31:25.430 --> 00:31:26.150 how this happens. 00:31:30.120 --> 00:31:31.490 So again, this is dynamic. 00:31:31.490 --> 00:31:33.830 And I want to show you a movie that shows you 00:31:33.830 --> 00:31:36.670 the dynamics of this process. 00:31:36.670 --> 00:31:39.620 So now this is an embryo that's been labeled 00:31:39.620 --> 00:31:41.540 with some of these fluorescent proteins 00:31:41.540 --> 00:31:44.400 that Professor Imperiali just introduced. 00:31:44.400 --> 00:31:46.730 One's green, that's the-- 00:31:46.730 --> 00:31:48.080 and it's shown here in green. 00:31:48.080 --> 00:31:50.810 And the other is a red fluorescent protein in red. 00:31:50.810 --> 00:31:54.410 The red fluorescent protein is marking individual cells. 00:31:54.410 --> 00:31:58.280 The green protein is a motor protein that generates force. 00:31:58.280 --> 00:32:02.360 And what you see is, where the motor protein is, 00:32:02.360 --> 00:32:04.910 this is where the tissue contracts. 00:32:04.910 --> 00:32:07.150 And this is where the tissue folds. 00:32:07.150 --> 00:32:08.270 OK. 00:32:08.270 --> 00:32:12.410 And so because we're able to see these proteins in action, 00:32:12.410 --> 00:32:16.110 we can infer how they're functioning during development 00:32:16.110 --> 00:32:22.470 to essentially program tissue shape. 00:32:22.470 --> 00:32:24.540 And there are many other opportunities 00:32:24.540 --> 00:32:26.880 where, even though we have the genome, 00:32:26.880 --> 00:32:31.170 we still don't understand how collectives of proteins, 00:32:31.170 --> 00:32:34.380 or collectives of cells, are sort of interacting 00:32:34.380 --> 00:32:39.600 with each other to sort of create emergent properties that 00:32:39.600 --> 00:32:43.080 are what are responsible for patterning something 00:32:43.080 --> 00:32:46.540 as large as a human. 00:32:46.540 --> 00:32:50.050 Another thing that we'll talk about is how cells divide. 00:32:50.050 --> 00:32:52.450 And this is another fruit fly embryo. 00:32:52.450 --> 00:32:54.940 And it's labeling histones. 00:32:54.940 --> 00:32:57.040 So it labels the DNA. 00:32:57.040 --> 00:33:01.920 And so you're seeing nuclei here divide sequentially. 00:33:01.920 --> 00:33:03.490 There'll be one more division. 00:33:03.490 --> 00:33:04.730 And then it's going to stop. 00:33:04.730 --> 00:33:05.230 OK. 00:33:05.230 --> 00:33:08.170 And my point here is that cell division 00:33:08.170 --> 00:33:12.850 during development and in adults is under exquisite control. 00:33:12.850 --> 00:33:14.320 OK. 00:33:14.320 --> 00:33:16.930 And a breakdown of this control is 00:33:16.930 --> 00:33:19.550 important in the progression of cancer. 00:33:19.550 --> 00:33:23.860 So we're going to talk about how cells control whether or not 00:33:23.860 --> 00:33:29.920 they divide, and how this is impacted in cancer cells. 00:33:29.920 --> 00:33:32.530 I also want to point out that this video is 00:33:32.530 --> 00:33:37.284 from Eric Wieschaus who is at Princeton University. 00:33:40.740 --> 00:33:41.240 OK. 00:33:41.240 --> 00:33:42.407 Want to just hit the lights. 00:33:42.407 --> 00:33:45.580 I have one last thing just to mention. 00:33:45.580 --> 00:33:48.970 So I just want to reinforce what Professor Imperiali said, 00:33:48.970 --> 00:33:50.740 we have a small class. 00:33:50.740 --> 00:33:53.770 So this is really an opportunity to have 00:33:53.770 --> 00:33:57.520 this be more interactive than it would be if we had 00:33:57.520 --> 00:34:00.230 like 300 people in the class. 00:34:00.230 --> 00:34:06.070 So I want to really encourage you guys to ask questions. 00:34:06.070 --> 00:34:09.350 Also if you have ideas, we would love to hear them. 00:34:09.350 --> 00:34:14.199 And I want to try one new thing this semester. 00:34:14.199 --> 00:34:16.690 So I find that students are a little hesitant 00:34:16.690 --> 00:34:18.610 to come to my office hours. 00:34:18.610 --> 00:34:23.000 So this year I want to hold what I'm calling running hours. 00:34:26.190 --> 00:34:30.560 So one thing that I really like to do is I like to run. 00:34:30.560 --> 00:34:33.949 And I've noticed that many of my students 00:34:33.949 --> 00:34:36.650 are also runners, because I'll like see them out 00:34:36.650 --> 00:34:38.300 around the river. 00:34:38.300 --> 00:34:42.920 And so I just want to hold sort of weekly running hours. 00:34:42.920 --> 00:34:48.580 I'm going to choose 3 o'clock, not three hour run, all right, 00:34:48.580 --> 00:34:52.000 3:00 PM on Fridays. 00:34:52.000 --> 00:34:53.450 And we'll just meet in my office. 00:34:57.500 --> 00:34:59.990 And so if you like to run, you can just meet there. 00:34:59.990 --> 00:35:03.560 We'll go on a run around the Charles. 00:35:03.560 --> 00:35:06.140 And this is not a competitive event. 00:35:06.140 --> 00:35:08.900 I'm not some fitness nut. 00:35:08.900 --> 00:35:13.610 I ran home last week, and I ate half a bag of Swedish fish 00:35:13.610 --> 00:35:14.630 on the way. 00:35:14.630 --> 00:35:17.000 So it's not a competition. 00:35:17.000 --> 00:35:19.430 It's just to try to get to know you guys 00:35:19.430 --> 00:35:24.123 and to try to break the ice in sort of a non-academic way. 00:35:24.123 --> 00:35:25.040 BARBARA IMPERIALI: OK. 00:35:25.040 --> 00:35:28.040 So I'm just going to wrap up here. 00:35:28.040 --> 00:35:30.590 So we bombed you with quite a lot of-- yes, over there. 00:35:30.590 --> 00:35:32.090 You want to know more about running. 00:35:32.090 --> 00:35:34.787 [INAUDIBLE] 00:35:34.787 --> 00:35:36.870 AUDIENCE: Will you still have normal office hours. 00:35:36.870 --> 00:35:39.850 PROFESSOR MARTIN: Yeah I'll have normal office hours. 00:35:39.850 --> 00:35:41.840 Yeah, or you could join me at CrossFit 00:35:41.840 --> 00:35:44.870 if you would like as well. 00:35:44.870 --> 00:35:47.870 We will both have office hours, and we will post them. 00:35:47.870 --> 00:35:50.840 And we welcome you to come visit us and, you know, 00:35:50.840 --> 00:35:53.760 find out more, tell us more about yourselves. 00:35:53.760 --> 00:35:56.990 We are fountains of information. 00:35:56.990 --> 00:36:00.660 So basically over the first half of the course, 00:36:00.660 --> 00:36:02.840 we tend to cover foundations. 00:36:02.840 --> 00:36:07.240 And so we build on biochemistry, one of my favorite subjects, 00:36:07.240 --> 00:36:09.840 where we cover all of the molecules of life. 00:36:09.840 --> 00:36:14.270 What are all the bits it takes to make a cell, lipids, sugars, 00:36:14.270 --> 00:36:16.310 proteins, nucleic acids. 00:36:16.310 --> 00:36:18.560 Then we synthesize them all together, 00:36:18.560 --> 00:36:21.650 where we show, in molecular biology, 00:36:21.650 --> 00:36:24.980 how the genome encodes the proteome, 00:36:24.980 --> 00:36:27.740 and what happens to the proteome after that. 00:36:27.740 --> 00:36:30.350 So you'll see me for all of those lectures. 00:36:30.350 --> 00:36:34.700 Then I will hand you over to Professor Martin for genetics, 00:36:34.700 --> 00:36:38.630 for the learning how to manipulate DNA. 00:36:38.630 --> 00:36:41.570 And we'll cap-off this first phase of work 00:36:41.570 --> 00:36:44.000 with cell signaling and understanding 00:36:44.000 --> 00:36:46.580 much more about dynamics of cells, 00:36:46.580 --> 00:36:49.010 as opposed to static building blocks. 00:36:49.010 --> 00:36:51.950 But you've got to understand the building blocks before you 00:36:51.950 --> 00:36:53.870 can understand the complexity. 00:36:53.870 --> 00:36:57.830 That's why I really like to cover those molecules 00:36:57.830 --> 00:36:59.030 at a reasonable depth. 00:36:59.030 --> 00:37:00.710 It's kind of ridiculous, 4 classes. 00:37:00.710 --> 00:37:02.970 But nevertheless, that's how we start. 00:37:02.970 --> 00:37:05.540 For some of you, you've seen some of it before. 00:37:05.540 --> 00:37:08.660 For others, you've seen none of it before. 00:37:08.660 --> 00:37:10.310 It doesn't matter. 00:37:10.310 --> 00:37:13.160 We will give you our flavor on it. 00:37:13.160 --> 00:37:15.110 If your chemistry is a little weak, 00:37:15.110 --> 00:37:17.640 I suggest you read the textbook. 00:37:17.640 --> 00:37:20.600 There's a couple of sections on just chemical covalent 00:37:20.600 --> 00:37:22.790 and non-covalent bonding, that you'll 00:37:22.790 --> 00:37:25.280 need to do the first P set. 00:37:25.280 --> 00:37:27.470 If your chemistry is strong, you're fine. 00:37:27.470 --> 00:37:29.900 If your chemistry is weak and you need a little help, 00:37:29.900 --> 00:37:31.700 I'll run an extra session next week. 00:37:31.700 --> 00:37:34.160 We can take care of every eventuality 00:37:34.160 --> 00:37:36.290 because you're a smaller class. 00:37:36.290 --> 00:37:39.390 And then we'll take it from there. 00:37:39.390 --> 00:37:41.300 And then what I really want to do 00:37:41.300 --> 00:37:44.490 is encourage you to do the reading. 00:37:44.490 --> 00:37:46.340 Make sure you're in a recitation. 00:37:46.340 --> 00:37:48.260 And next time, but it's in the sidebar, 00:37:48.260 --> 00:37:50.930 I'd like you to take a look at the sliding scale which 00:37:50.930 --> 00:37:54.710 shows you the dimensions of molecules, macromolecules, 00:37:54.710 --> 00:37:58.280 and organisms, which I find rather cool, even though it's 00:37:58.280 --> 00:38:00.090 probably built for high school students. 00:38:00.090 --> 00:38:00.590 OK. 00:38:00.590 --> 00:38:03.010 That's it from us for now.