1 00:00:04,710 --> 00:00:03,189 the dragon spacecraft launching soon to 2 00:00:06,869 --> 00:00:04,720 the international space station is 3 00:00:09,190 --> 00:00:06,879 carrying supplies for the crew and a 4 00:00:11,430 --> 00:00:09,200 number of science experiments among them 5 00:00:13,190 --> 00:00:11,440 is a new hardware for new research 6 00:00:16,470 --> 00:00:13,200 that's focusing on crystallization of 7 00:00:19,109 --> 00:00:16,480 the cystic fibrosis protein which could 8 00:00:21,830 --> 00:00:19,119 help researchers develop better drugs to 9 00:00:24,550 --> 00:00:21,840 treat the disease joining us now we have 10 00:00:26,630 --> 00:00:24,560 principal investigator dr stephen aller 11 00:00:28,630 --> 00:00:26,640 of the advancing membrane protein 12 00:00:31,429 --> 00:00:28,640 crystallization by using microgravity 13 00:00:33,830 --> 00:00:31,439 experiment so very briefly can you just 14 00:00:37,110 --> 00:00:33,840 describe for us what causes cystic 15 00:00:39,430 --> 00:00:37,120 fibrosis and also how it is treated 16 00:00:41,990 --> 00:00:39,440 cystic fibrosis is 17 00:00:43,830 --> 00:00:42,000 a point mutation in a protein and 90 18 00:00:45,590 --> 00:00:43,840 percent of the patients in which the 19 00:00:47,350 --> 00:00:45,600 protein is misfolded 20 00:00:49,190 --> 00:00:47,360 and none of it gets to the cell surface 21 00:00:50,869 --> 00:00:49,200 where it's required to function 22 00:00:55,189 --> 00:00:50,879 its normal function is a chloride 23 00:00:57,029 --> 00:00:55,199 channel and allows plenty of water to uh 24 00:00:59,270 --> 00:00:57,039 to flow and 25 00:01:02,630 --> 00:00:59,280 lubricate the lungs and without this 26 00:01:05,429 --> 00:01:02,640 protein called cftr uh people develop 27 00:01:08,230 --> 00:01:05,439 very sticky mucous lungs uh and that 28 00:01:10,070 --> 00:01:08,240 results in infection and so we're trying 29 00:01:11,670 --> 00:01:10,080 to study the three-dimensional structure 30 00:01:13,030 --> 00:01:11,680 of this protein in order to understand 31 00:01:14,230 --> 00:01:13,040 how it works and how to correct the 32 00:01:17,350 --> 00:01:14,240 defects 33 00:01:19,910 --> 00:01:17,360 so why the focus on crystallizing the 34 00:01:22,149 --> 00:01:19,920 proteins for such treatment 35 00:01:24,390 --> 00:01:22,159 so a lot of drug screens that companies 36 00:01:26,789 --> 00:01:24,400 do are basically brute force and looking 37 00:01:29,270 --> 00:01:26,799 for an effect and they don't emphasize 38 00:01:31,190 --> 00:01:29,280 the mechanism by which drugs work and 39 00:01:33,510 --> 00:01:31,200 one of the important ways to learn by 40 00:01:35,350 --> 00:01:33,520 which drugs work is to see the 41 00:01:37,429 --> 00:01:35,360 the three-dimensional shape of the 42 00:01:39,990 --> 00:01:37,439 targets that the drugs bind to 43 00:01:42,389 --> 00:01:40,000 and we don't have any idea about the the 44 00:01:44,710 --> 00:01:42,399 atomic structure of this cystic fibrosis 45 00:01:46,550 --> 00:01:44,720 protein we have one structure of very 46 00:01:48,310 --> 00:01:46,560 close relative of it 47 00:01:50,069 --> 00:01:48,320 but right now we don't have any idea 48 00:01:52,550 --> 00:01:50,079 what the protein looks like particularly 49 00:01:54,710 --> 00:01:52,560 in the region where it is misfolded so 50 00:01:57,590 --> 00:01:54,720 if we could determine the shape of that 51 00:01:59,590 --> 00:01:57,600 to an atomic detail we can learn how to 52 00:02:01,749 --> 00:01:59,600 better correct the defect 53 00:02:04,069 --> 00:02:01,759 much more specifically and potent 54 00:02:06,389 --> 00:02:04,079 potently to get better drugs 55 00:02:07,190 --> 00:02:06,399 so can you explain to me also how is 56 00:02:10,790 --> 00:02:07,200 this 57 00:02:12,869 --> 00:02:10,800 experiment going to be working on orbit 58 00:02:15,030 --> 00:02:12,879 okay so the the general idea that we're 59 00:02:16,470 --> 00:02:15,040 testing is similar to other projects 60 00:02:19,030 --> 00:02:16,480 which are going up 61 00:02:21,270 --> 00:02:19,040 is that in space when you don't have 62 00:02:23,270 --> 00:02:21,280 gravity we don't have any convection 63 00:02:25,589 --> 00:02:23,280 forces these are like forces of wind 64 00:02:27,270 --> 00:02:25,599 which are in in the fluids and they're 65 00:02:28,949 --> 00:02:27,280 actually very strong forces that are 66 00:02:30,790 --> 00:02:28,959 banging around all the molecules that 67 00:02:32,150 --> 00:02:30,800 happens here in the ground and it makes 68 00:02:33,589 --> 00:02:32,160 it really challenging for protein 69 00:02:35,750 --> 00:02:33,599 crystals to form 70 00:02:38,070 --> 00:02:35,760 if you put a crystallization experiment 71 00:02:40,229 --> 00:02:38,080 in space with specialized hardware you 72 00:02:42,070 --> 00:02:40,239 remove this convection force and it 73 00:02:44,150 --> 00:02:42,080 gives the protein crystals much more 74 00:02:47,110 --> 00:02:44,160 time to form really really perfect 75 00:02:49,030 --> 00:02:47,120 lattices and for difficult proteins like 76 00:02:51,589 --> 00:02:49,040 the cystic fibrosis protein and two 77 00:02:53,430 --> 00:02:51,599 other relatives that we're studying 78 00:02:55,270 --> 00:02:53,440 they don't form very well ordered 79 00:02:57,190 --> 00:02:55,280 crystals on the ground and we're 80 00:02:59,270 --> 00:02:57,200 exploring the hypothesis that this 81 00:03:01,430 --> 00:02:59,280 microgravity will allow much much more 82 00:03:03,030 --> 00:03:01,440 perfect crystals to form and give us a 83 00:03:05,430 --> 00:03:03,040 lot more detailed information about the 84 00:03:07,030 --> 00:03:05,440 proteins so growing these crystals in 85 00:03:08,470 --> 00:03:07,040 space is better than on the ground and 86 00:03:10,550 --> 00:03:08,480 so we're going to be able to take 87 00:03:12,550 --> 00:03:10,560 advantage of that microgravity 88 00:03:14,710 --> 00:03:12,560 environment and aboard the international 89 00:03:16,869 --> 00:03:14,720 space station to conduct this experiment 90 00:03:18,790 --> 00:03:16,879 that's very good can you also tell me 91 00:03:19,990 --> 00:03:18,800 how long is it going to take to grow 92 00:03:21,270 --> 00:03:20,000 these crystals and when do they come 93 00:03:23,509 --> 00:03:21,280 home 94 00:03:25,910 --> 00:03:23,519 uh mission is scheduled to come back in 95 00:03:27,990 --> 00:03:25,920 july okay so that's several months and 96 00:03:30,630 --> 00:03:28,000 we need that extra time 97 00:03:32,949 --> 00:03:30,640 because the process is much slower 98 00:03:34,630 --> 00:03:32,959 so up until you know we had the space 99 00:03:36,869 --> 00:03:34,640 shuttle program which was limited to a 100 00:03:37,990 --> 00:03:36,879 very short duration a lot of this wasn't 101 00:03:39,589 --> 00:03:38,000 possible 102 00:03:41,270 --> 00:03:39,599 but because we have the resources on the 103 00:03:44,309 --> 00:03:41,280 space station it's up there for many 104 00:03:46,949 --> 00:03:44,319 many months we now have capabilities to 105 00:03:48,710 --> 00:03:46,959 allow experiments to go for much longer 106 00:03:50,309 --> 00:03:48,720 and hopefully capture crystallization 107 00:03:51,350 --> 00:03:50,319 processes which are which are much 108 00:03:52,949 --> 00:03:51,360 slower 109 00:03:55,270 --> 00:03:52,959 to happen 110 00:03:57,190 --> 00:03:55,280 can you tell me also what will become of 111 00:03:58,550 --> 00:03:57,200 these crystals during this flight once 112 00:04:00,470 --> 00:03:58,560 they are returned 113 00:04:02,070 --> 00:04:00,480 well hopefully when they are when 114 00:04:04,550 --> 00:04:02,080 they're they'll be returned in 115 00:04:07,190 --> 00:04:04,560 specialized hardware and and recovered 116 00:04:09,830 --> 00:04:07,200 uh they splashed down in the ocean and 117 00:04:14,070 --> 00:04:09,840 recovered by a special team uh they're 118 00:04:15,110 --> 00:04:14,080 flown in a uh uh um a jet 119 00:04:17,030 --> 00:04:15,120 that 120 00:04:19,509 --> 00:04:17,040 handles them very carefully 121 00:04:22,150 --> 00:04:19,519 and then my group will one by one 122 00:04:25,350 --> 00:04:22,160 examine the crystals that are in them 123 00:04:27,030 --> 00:04:25,360 and protect them from a process called 124 00:04:28,710 --> 00:04:27,040 cryo protection to protect them from 125 00:04:30,710 --> 00:04:28,720 damage during freezing 126 00:04:33,110 --> 00:04:30,720 and then we will ship them to u.s 127 00:04:34,870 --> 00:04:33,120 synchrotrons for data collection and 128 00:04:37,830 --> 00:04:34,880 synchrotrons are very critical for our 129 00:04:40,310 --> 00:04:37,840 proteins because they offer us very high 130 00:04:42,230 --> 00:04:40,320 intensity x-ray beam 131 00:04:44,950 --> 00:04:42,240 and much better data quality than what 132 00:04:45,909 --> 00:04:44,960 is possible with a lower intensity home 133 00:04:47,590 --> 00:04:45,919 source 134 00:04:49,990 --> 00:04:47,600 so we will collect the data from the 135 00:04:52,390 --> 00:04:50,000 crystals and in some cases compare them 136 00:04:54,550 --> 00:04:52,400 to earth-grown crystals uh in one case 137 00:04:57,189 --> 00:04:54,560 where we have enough protein to do that 138 00:04:59,350 --> 00:04:57,199 and we will know with high confidence 139 00:05:01,670 --> 00:04:59,360 just the effects of microgravity on 140 00:05:03,270 --> 00:05:01,680 these specific proteins 141 00:05:05,909 --> 00:05:03,280 best of luck to you and thanks again for