1 00:00:05,000 --> 00:00:08,740 PROFESSOR: If you're a teacher and you're 2 00:00:08,740 --> 00:00:12,880 inventing a course for the first time, or revising it a lot, 3 00:00:12,880 --> 00:00:15,010 you sit down with your teaching partners 4 00:00:15,010 --> 00:00:19,320 and you put on the table all the ideas. 5 00:00:19,320 --> 00:00:24,370 Teaching, you've got an ever-expanding universe 6 00:00:24,370 --> 00:00:25,960 of knowledge out there, and you have 7 00:00:25,960 --> 00:00:29,450 to cherry-pick the things that are going to be important. 8 00:00:29,450 --> 00:00:31,910 It has to hang together. 9 00:00:31,910 --> 00:00:35,500 One of the strategies JoAnne and I thought, 10 00:00:35,500 --> 00:00:38,860 when we went into the current iteration of teaching 5.07 11 00:00:38,860 --> 00:00:44,650 biological chemistry, was to abandon completely, 12 00:00:44,650 --> 00:00:50,680 higher eukaryotes, namely us, because genome sequencing 13 00:00:50,680 --> 00:00:58,390 projects had sequenced so many bacteria that one could create 14 00:00:58,390 --> 00:01:01,960 an entire course in biochemistry that would be very meaningful, 15 00:01:01,960 --> 00:01:05,390 just focusing on microorganisms. 16 00:01:05,390 --> 00:01:09,650 We spent a couple of days reading and thinking about it. 17 00:01:09,650 --> 00:01:12,800 That would be the course JoAnne and I would teach, 18 00:01:12,800 --> 00:01:16,040 if it weren't for the fact that we actually 19 00:01:16,040 --> 00:01:19,880 have-- feel as though we have a commitment to students that 20 00:01:19,880 --> 00:01:22,220 are going to go on to medical school 21 00:01:22,220 --> 00:01:27,380 and therefore, if we avoided mammalian biochemistry, 22 00:01:27,380 --> 00:01:30,130 students wouldn't know anything about the mitochondria 23 00:01:30,130 --> 00:01:33,620 and organelles, and things like that that 24 00:01:33,620 --> 00:01:36,380 are associated with eukaryotes. 25 00:01:36,380 --> 00:01:41,270 We wouldn't be able to make these connections to disease, 26 00:01:41,270 --> 00:01:43,670 the physiological scenarios. 27 00:01:43,670 --> 00:01:46,430 Nevertheless, why were we so interested in bacteria? 28 00:01:46,430 --> 00:01:48,200 What would be an interesting story, 29 00:01:48,200 --> 00:01:53,130 that I might be able to tell you, if we had taken that path. 30 00:01:53,130 --> 00:01:55,520 So we have a fellow in biological engineering, 31 00:01:55,520 --> 00:01:57,680 named Eric Alm. 32 00:01:57,680 --> 00:02:03,460 And he is an informaticist and an engineer, 33 00:02:03,460 --> 00:02:06,770 and an extremely good chemist. 34 00:02:06,770 --> 00:02:09,669 He really knows his pathways. 35 00:02:09,669 --> 00:02:13,340 When he looks at a cell, he thinks 36 00:02:13,340 --> 00:02:16,610 about what it is, but also where it came from, 37 00:02:16,610 --> 00:02:21,990 in terms of how it evolved from precursors, its family tree, 38 00:02:21,990 --> 00:02:24,030 so to speak. 39 00:02:24,030 --> 00:02:26,570 One of the most interesting organisms 40 00:02:26,570 --> 00:02:28,940 that he's published on, not too long ago, 41 00:02:28,940 --> 00:02:32,820 is an organism called, Desulforudis. 42 00:02:32,820 --> 00:02:38,980 And this would be a wonderful biochemistry course in itself. 43 00:02:38,980 --> 00:02:45,200 He wondered, if he went out and dug up a cubic meter of dirt-- 44 00:02:45,200 --> 00:02:50,890 and outside MIT-- and if he did 16S RNA sequencing, 45 00:02:50,890 --> 00:02:54,430 how many living things would be there, many thousands, maybe 46 00:02:54,430 --> 00:02:56,270 10,000. 47 00:02:56,270 --> 00:02:59,680 Then he asked the question, what if you went down 100 meters, 48 00:02:59,680 --> 00:03:02,050 you know, maybe you see 1,000. 49 00:03:02,050 --> 00:03:04,240 But what if you go down until there's really 50 00:03:04,240 --> 00:03:06,160 only one thing there. 51 00:03:06,160 --> 00:03:10,810 And that's what he did, going down two miles into the ground. 52 00:03:10,810 --> 00:03:16,240 And there was a single, species ecosystem called, Desulforudis. 53 00:03:16,240 --> 00:03:17,650 And I remember seeing this paper, 54 00:03:17,650 --> 00:03:19,190 and I brought it over to JoAnne. 55 00:03:19,190 --> 00:03:21,880 I was so excited because the last picture 56 00:03:21,880 --> 00:03:26,650 showed its metabolic network, its metabolic pathways. 57 00:03:26,650 --> 00:03:28,450 It had everything. 58 00:03:28,450 --> 00:03:29,710 And it makes sense. 59 00:03:29,710 --> 00:03:32,840 It can't rely on other things. 60 00:03:32,840 --> 00:03:35,770 For example, we can't make all of our amino acids. 61 00:03:35,770 --> 00:03:38,110 We got to get them from food that we eat, 62 00:03:38,110 --> 00:03:40,960 or in our co-factors, some of our vitamins 63 00:03:40,960 --> 00:03:44,410 are made by the bacteria in our gut. 64 00:03:44,410 --> 00:03:50,410 So, if all the bacteria disappear, we would too. 65 00:03:50,410 --> 00:03:52,720 So we rely on other things, but Desulforudis 66 00:03:52,720 --> 00:03:54,680 doesn't rely on anything. 67 00:03:54,680 --> 00:03:59,500 So when you look at it's biochemical networks, 68 00:03:59,500 --> 00:04:01,990 what you see is that it can fix nitrogen. It 69 00:04:01,990 --> 00:04:05,320 can take N2 and convert it NH3, and then 70 00:04:05,320 --> 00:04:07,180 put that into amino acids, and it can 71 00:04:07,180 --> 00:04:09,160 make all of its amino acids. 72 00:04:09,160 --> 00:04:12,670 It has a really good pentose phosphate pathway. 73 00:04:12,670 --> 00:04:15,640 It actually uses radiation in a strange way 74 00:04:15,640 --> 00:04:19,240 to generate some of the energy that it needs. 75 00:04:19,240 --> 00:04:21,760 It uses it to generate carbon monoxide. 76 00:04:21,760 --> 00:04:25,930 Ultimately, that CO is going to form an acetyl group that 77 00:04:25,930 --> 00:04:29,200 will be able to generate all of the organic material 78 00:04:29,200 --> 00:04:32,230 inside the Desulforudis. 79 00:04:32,230 --> 00:04:36,730 It's got all kinds of electron transport pathways. 80 00:04:36,730 --> 00:04:40,510 So it's developed enormous versatility 81 00:04:40,510 --> 00:04:43,420 by being a single-species ecosystem. 82 00:04:43,420 --> 00:04:46,510 So, again, this was a course where 83 00:04:46,510 --> 00:04:50,890 we had to make a compromise because of our clientele. 84 00:04:50,890 --> 00:04:52,660 Teachers have to think about that. 85 00:04:52,660 --> 00:04:56,650 We have to teach to what the people need in order 86 00:04:56,650 --> 00:04:58,850 to go on to the next step. 87 00:04:58,850 --> 00:05:00,580 But as sort of a closing thought, 88 00:05:00,580 --> 00:05:02,140 I think that it would be wonderful 89 00:05:02,140 --> 00:05:06,370 for next-generation biochemists to really turn their attention 90 00:05:06,370 --> 00:05:11,740 to the microbial world, to teach this vast biochemistry 91 00:05:11,740 --> 00:05:17,630 and understand how bacteria effortlessly, 92 00:05:17,630 --> 00:05:22,430 swap biochemical pathways, pick-up entire biochemical 93 00:05:22,430 --> 00:05:24,860 pathways without even breaking a sweat. 94 00:05:24,860 --> 00:05:27,860 Whenever they find themselves stressed, 95 00:05:27,860 --> 00:05:31,570 they just pick up a new pathway and they survive.