[Script Info] Title: [Events] Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text Dialogue: 0,0:00:02.42,0:00:03.68,Default,,0000,0000,0000,,I live in Utah, Dialogue: 0,0:00:03.71,0:00:06.56,Default,,0000,0000,0000,,a place known for having\Nsome of the most awe-inspiring Dialogue: 0,0:00:06.58,0:00:09.14,Default,,0000,0000,0000,,natural landscapes on this planet. Dialogue: 0,0:00:09.17,0:00:12.64,Default,,0000,0000,0000,,It's easy to be overwhelmed\Nby these amazing views, Dialogue: 0,0:00:12.67,0:00:16.52,Default,,0000,0000,0000,,and to be really fascinated by these\Nsometimes alien-looking formations. Dialogue: 0,0:00:16.54,0:00:20.18,Default,,0000,0000,0000,,As a scientist, I love\Nobserving the natural world. Dialogue: 0,0:00:20.21,0:00:21.98,Default,,0000,0000,0000,,But as a cell biologist, Dialogue: 0,0:00:22.00,0:00:24.81,Default,,0000,0000,0000,,I'm much more interested\Nin understanding the natural world Dialogue: 0,0:00:24.83,0:00:27.04,Default,,0000,0000,0000,,at a much, much smaller scale. Dialogue: 0,0:00:27.92,0:00:30.73,Default,,0000,0000,0000,,I'm a molecular animator,\Nand I work with other researchers Dialogue: 0,0:00:30.75,0:00:33.64,Default,,0000,0000,0000,,to create visualizations\Nof molecules that are so small, Dialogue: 0,0:00:33.67,0:00:35.27,Default,,0000,0000,0000,,they're essentially invisible. Dialogue: 0,0:00:35.29,0:00:38.14,Default,,0000,0000,0000,,These molecules are smaller\Nthan the wavelength of light, Dialogue: 0,0:00:38.17,0:00:40.41,Default,,0000,0000,0000,,which means that we can\Nnever see them directly, Dialogue: 0,0:00:40.43,0:00:42.48,Default,,0000,0000,0000,,even with the best light microscopes. Dialogue: 0,0:00:42.50,0:00:44.64,Default,,0000,0000,0000,,So how do I create\Nvisualizations of things Dialogue: 0,0:00:44.67,0:00:46.64,Default,,0000,0000,0000,,that are so small we can't see them? Dialogue: 0,0:00:46.67,0:00:48.81,Default,,0000,0000,0000,,Scientists, like my collaborators, Dialogue: 0,0:00:48.83,0:00:50.93,Default,,0000,0000,0000,,can spend their entire\Nprofessional careers Dialogue: 0,0:00:50.96,0:00:53.52,Default,,0000,0000,0000,,working to understand\None molecular process. Dialogue: 0,0:00:53.54,0:00:56.02,Default,,0000,0000,0000,,To do this, they carry out\Na series of experiments Dialogue: 0,0:00:56.04,0:00:59.14,Default,,0000,0000,0000,,that each can tell us\Na small piece of the puzzle. Dialogue: 0,0:00:59.17,0:01:01.93,Default,,0000,0000,0000,,One kind of experiment\Ncan tell us about the protein shape, Dialogue: 0,0:01:01.96,0:01:03.23,Default,,0000,0000,0000,,while another can tell us Dialogue: 0,0:01:03.25,0:01:05.54,Default,,0000,0000,0000,,about what other proteins\Nit might interact with, Dialogue: 0,0:01:05.56,0:01:08.46,Default,,0000,0000,0000,,and another can tell us\Nabout where it can be found in a cell. Dialogue: 0,0:01:08.49,0:01:12.48,Default,,0000,0000,0000,,And all of these bits of information\Ncan be used to come up with a hypothesis, Dialogue: 0,0:01:12.50,0:01:15.58,Default,,0000,0000,0000,,a story, essentially,\Nof how a molecule might work. Dialogue: 0,0:01:17.00,0:01:20.93,Default,,0000,0000,0000,,My job is to take these ideas\Nand turn them into an animation. Dialogue: 0,0:01:20.96,0:01:22.23,Default,,0000,0000,0000,,This can be tricky, Dialogue: 0,0:01:22.25,0:01:25.48,Default,,0000,0000,0000,,because it turns out that molecules\Ncan do some pretty crazy things. Dialogue: 0,0:01:25.50,0:01:28.85,Default,,0000,0000,0000,,But these animations\Ncan be incredibly useful for researchers Dialogue: 0,0:01:28.88,0:01:31.98,Default,,0000,0000,0000,,to communicate their ideas\Nof how these molecules work. Dialogue: 0,0:01:32.00,0:01:34.77,Default,,0000,0000,0000,,They can also allow us\Nto see the molecular world Dialogue: 0,0:01:34.79,0:01:36.35,Default,,0000,0000,0000,,through their eyes. Dialogue: 0,0:01:36.38,0:01:38.31,Default,,0000,0000,0000,,I'd like to show you some animations, Dialogue: 0,0:01:38.33,0:01:41.85,Default,,0000,0000,0000,,a brief tour of what I consider to be\Nsome of the natural wonders Dialogue: 0,0:01:41.88,0:01:43.56,Default,,0000,0000,0000,,of the molecular world. Dialogue: 0,0:01:43.58,0:01:45.56,Default,,0000,0000,0000,,First off, this is an immune cell. Dialogue: 0,0:01:45.58,0:01:48.48,Default,,0000,0000,0000,,These kinds of cells need to go\Ncrawling around in our bodies Dialogue: 0,0:01:48.50,0:01:51.52,Default,,0000,0000,0000,,in order to find invaders\Nlike pathogenic bacteria. Dialogue: 0,0:01:51.54,0:01:54.64,Default,,0000,0000,0000,,This movement is powered\Nby one of my favorite proteins Dialogue: 0,0:01:54.67,0:01:55.93,Default,,0000,0000,0000,,called actin, Dialogue: 0,0:01:55.96,0:01:58.43,Default,,0000,0000,0000,,which is part of what's known\Nas the cytoskeleton. Dialogue: 0,0:01:58.46,0:02:00.10,Default,,0000,0000,0000,,Unlike our skeletons, Dialogue: 0,0:02:00.12,0:02:03.85,Default,,0000,0000,0000,,actin filaments are constantly\Nbeing built and taken apart. Dialogue: 0,0:02:03.88,0:02:07.27,Default,,0000,0000,0000,,The actin cytoskeleton plays\Nincredibly important roles in our cells. Dialogue: 0,0:02:07.29,0:02:09.06,Default,,0000,0000,0000,,They allow them to change shape, Dialogue: 0,0:02:09.08,0:02:11.48,Default,,0000,0000,0000,,to move around, to adhere to surfaces, Dialogue: 0,0:02:11.50,0:02:13.93,Default,,0000,0000,0000,,and also to gobble up bacteria. Dialogue: 0,0:02:13.96,0:02:16.56,Default,,0000,0000,0000,,Actin is also involved\Nin a different kind of movement. Dialogue: 0,0:02:16.58,0:02:19.77,Default,,0000,0000,0000,,In our muscle cells, actin structures\Nform these regular filaments Dialogue: 0,0:02:19.79,0:02:21.31,Default,,0000,0000,0000,,that look kind of like fabric. Dialogue: 0,0:02:21.33,0:02:24.27,Default,,0000,0000,0000,,When our muscles contract,\Nthese filaments are pulled together Dialogue: 0,0:02:24.29,0:02:26.31,Default,,0000,0000,0000,,and they go back\Nto their original position Dialogue: 0,0:02:26.33,0:02:27.81,Default,,0000,0000,0000,,when our muscles relax. Dialogue: 0,0:02:27.83,0:02:31.06,Default,,0000,0000,0000,,Other parts of the cytoskeleton,\Nin this case microtubules, Dialogue: 0,0:02:31.08,0:02:33.77,Default,,0000,0000,0000,,are responsible for long-range\Ntransportation. Dialogue: 0,0:02:33.79,0:02:36.43,Default,,0000,0000,0000,,They can be thought of\Nas basically cellular highways Dialogue: 0,0:02:36.46,0:02:39.81,Default,,0000,0000,0000,,that are used to move things\Nfrom one side of the cell to the other. Dialogue: 0,0:02:39.83,0:02:42.60,Default,,0000,0000,0000,,Unlike our roads,\Nmicrotubules grow and shrink, Dialogue: 0,0:02:42.62,0:02:44.06,Default,,0000,0000,0000,,appearing when they're needed Dialogue: 0,0:02:44.08,0:02:46.43,Default,,0000,0000,0000,,and disappearing when their job is done. Dialogue: 0,0:02:46.46,0:02:48.89,Default,,0000,0000,0000,,The molecular version of semitrucks Dialogue: 0,0:02:48.92,0:02:51.48,Default,,0000,0000,0000,,are proteins aptly named motor proteins, Dialogue: 0,0:02:51.50,0:02:53.98,Default,,0000,0000,0000,,that can walk along microtubules, Dialogue: 0,0:02:54.00,0:02:56.68,Default,,0000,0000,0000,,dragging sometimes huge cargoes, Dialogue: 0,0:02:56.71,0:02:58.52,Default,,0000,0000,0000,,like organelles, behind them. Dialogue: 0,0:02:58.54,0:03:01.39,Default,,0000,0000,0000,,This particular motor protein\Nis known as dynein, Dialogue: 0,0:03:01.42,0:03:03.85,Default,,0000,0000,0000,,and its known to be able\Nto work together in groups Dialogue: 0,0:03:03.88,0:03:07.31,Default,,0000,0000,0000,,that almost look, at least to me,\Nlike a chariot of horses. Dialogue: 0,0:03:07.33,0:03:11.18,Default,,0000,0000,0000,,As you see, the cell is this incredibly\Nchanging, dynamic place, Dialogue: 0,0:03:11.21,0:03:14.64,Default,,0000,0000,0000,,where things are constantly\Nbeing built and disassembled. Dialogue: 0,0:03:14.67,0:03:16.02,Default,,0000,0000,0000,,But some of these structures Dialogue: 0,0:03:16.04,0:03:18.14,Default,,0000,0000,0000,,are harder to take apart\Nthan others, though. Dialogue: 0,0:03:18.17,0:03:20.10,Default,,0000,0000,0000,,And special forces need to be brought in Dialogue: 0,0:03:20.12,0:03:23.56,Default,,0000,0000,0000,,in order to make sure that structures\Nare taken apart in a timely manner. Dialogue: 0,0:03:23.58,0:03:26.31,Default,,0000,0000,0000,,That job is done in part\Nby proteins like these. Dialogue: 0,0:03:26.33,0:03:27.85,Default,,0000,0000,0000,,These donut-shaped proteins, Dialogue: 0,0:03:27.88,0:03:29.89,Default,,0000,0000,0000,,of which there are many types in the cell, Dialogue: 0,0:03:29.92,0:03:31.98,Default,,0000,0000,0000,,all seem to act to rip apart structures Dialogue: 0,0:03:32.00,0:03:35.39,Default,,0000,0000,0000,,by basically pulling individual proteins\Nthrough a central hole. Dialogue: 0,0:03:35.42,0:03:37.98,Default,,0000,0000,0000,,When these kinds of proteins\Ndon't work properly, Dialogue: 0,0:03:38.00,0:03:40.73,Default,,0000,0000,0000,,the types of proteins\Nthat are supposed to get taken apart Dialogue: 0,0:03:40.75,0:03:43.18,Default,,0000,0000,0000,,can sometimes stick together and aggregate Dialogue: 0,0:03:43.21,0:03:47.39,Default,,0000,0000,0000,,and that can give rise\Nto terrible diseases, such as Alzheimer's. Dialogue: 0,0:03:47.42,0:03:49.43,Default,,0000,0000,0000,,And now let's take a look at the nucleus, Dialogue: 0,0:03:49.46,0:03:52.39,Default,,0000,0000,0000,,which houses our genome\Nin the form of DNA. Dialogue: 0,0:03:52.42,0:03:53.85,Default,,0000,0000,0000,,In all of our cells, Dialogue: 0,0:03:53.88,0:03:58.18,Default,,0000,0000,0000,,our DNA is cared for and maintained\Nby a diverse set of proteins. Dialogue: 0,0:03:58.21,0:04:01.02,Default,,0000,0000,0000,,DNA is wound around proteins\Ncalled histones, Dialogue: 0,0:04:01.04,0:04:05.35,Default,,0000,0000,0000,,which enable cells to pack\Nlarge amounts of DNA into our nucleus. Dialogue: 0,0:04:05.38,0:04:08.43,Default,,0000,0000,0000,,These machines\Nare called chromatin remodelers Dialogue: 0,0:04:08.46,0:04:11.18,Default,,0000,0000,0000,,and the way they work\Nis that they basically scoot the DNA Dialogue: 0,0:04:11.21,0:04:12.48,Default,,0000,0000,0000,,around these histones Dialogue: 0,0:04:12.50,0:04:16.35,Default,,0000,0000,0000,,and they allow new pieces of DNA\Nto become exposed. Dialogue: 0,0:04:16.38,0:04:19.31,Default,,0000,0000,0000,,This DNA can then be recognized\Nby other machinery. Dialogue: 0,0:04:19.33,0:04:21.85,Default,,0000,0000,0000,,In this case, this large molecular machine Dialogue: 0,0:04:21.88,0:04:23.56,Default,,0000,0000,0000,,is looking for a segment of DNA Dialogue: 0,0:04:23.58,0:04:25.89,Default,,0000,0000,0000,,that tells it it's\Nat the beginning of a gene. Dialogue: 0,0:04:25.92,0:04:27.60,Default,,0000,0000,0000,,Once it finds a segment, Dialogue: 0,0:04:27.62,0:04:30.39,Default,,0000,0000,0000,,it basically undergoes\Na series of shape changes Dialogue: 0,0:04:30.42,0:04:32.52,Default,,0000,0000,0000,,which enables it to bring in\Nother machinery Dialogue: 0,0:04:32.54,0:04:36.68,Default,,0000,0000,0000,,that in turn allows a gene\Nto get turned on or transcribed. Dialogue: 0,0:04:36.71,0:04:39.81,Default,,0000,0000,0000,,This has to be a very\Ntightly regulated process Dialogue: 0,0:04:39.83,0:04:42.60,Default,,0000,0000,0000,,because turning on the wrong gene\Nat the wrong time Dialogue: 0,0:04:42.62,0:04:45.27,Default,,0000,0000,0000,,can have disastrous consequences. Dialogue: 0,0:04:45.29,0:04:48.10,Default,,0000,0000,0000,,Scientists are now able\Nto use protein machines Dialogue: 0,0:04:48.12,0:04:49.56,Default,,0000,0000,0000,,to edit genomes. Dialogue: 0,0:04:49.58,0:04:52.02,Default,,0000,0000,0000,,I'm sure all of you have heard of CRISPR. Dialogue: 0,0:04:52.04,0:04:54.85,Default,,0000,0000,0000,,CRISPR takes advantage\Nof a protein known as Cas9, Dialogue: 0,0:04:54.88,0:04:57.81,Default,,0000,0000,0000,,which can be engineered\Nto recognize and cut Dialogue: 0,0:04:57.83,0:05:00.23,Default,,0000,0000,0000,,a very specific sequence of DNA. Dialogue: 0,0:05:00.25,0:05:01.52,Default,,0000,0000,0000,,In this example, Dialogue: 0,0:05:01.54,0:05:05.52,Default,,0000,0000,0000,,two Cas9 proteins are being used\Nto excise a problematic piece of DNA. Dialogue: 0,0:05:05.54,0:05:09.02,Default,,0000,0000,0000,,For example, a part of a gene\Nthat may give rise to a disease. Dialogue: 0,0:05:09.04,0:05:10.52,Default,,0000,0000,0000,,Cellular machinery is then used Dialogue: 0,0:05:10.54,0:05:14.06,Default,,0000,0000,0000,,to basically glue two ends\Nof the DNA back together. Dialogue: 0,0:05:14.08,0:05:15.35,Default,,0000,0000,0000,,As a molecular animator, Dialogue: 0,0:05:15.38,0:05:18.68,Default,,0000,0000,0000,,one of my biggest challenges\Nis visualizing uncertainty. Dialogue: 0,0:05:18.71,0:05:22.02,Default,,0000,0000,0000,,All of the animations I've shown to you\Nrepresent hypotheses, Dialogue: 0,0:05:22.04,0:05:24.31,Default,,0000,0000,0000,,how my collaborators think\Na process works, Dialogue: 0,0:05:24.33,0:05:26.68,Default,,0000,0000,0000,,based on the best information\Nthat they have. Dialogue: 0,0:05:26.71,0:05:28.68,Default,,0000,0000,0000,,But for a lot of molecular processes, Dialogue: 0,0:05:28.71,0:05:31.68,Default,,0000,0000,0000,,we're still really at the early stages\Nof understanding things, Dialogue: 0,0:05:31.71,0:05:33.02,Default,,0000,0000,0000,,and there's a lot to learn. Dialogue: 0,0:05:33.04,0:05:34.31,Default,,0000,0000,0000,,The truth is Dialogue: 0,0:05:34.33,0:05:38.29,Default,,0000,0000,0000,,that these invisible molecular worlds\Nare vast and largely unexplored. Dialogue: 0,0:05:39.46,0:05:41.52,Default,,0000,0000,0000,,To me, these molecular landscapes Dialogue: 0,0:05:41.54,0:05:44.93,Default,,0000,0000,0000,,are just as exciting to explore\Nas a natural world Dialogue: 0,0:05:44.96,0:05:47.35,Default,,0000,0000,0000,,that's visible all around us. Dialogue: 0,0:05:47.38,0:05:48.64,Default,,0000,0000,0000,,Thank you. Dialogue: 0,0:05:48.67,0:05:51.79,Default,,0000,0000,0000,,(Applause)