WEBVTT 00:00:02.420 --> 00:00:03.643 I live in Utah, 00:00:03.667 --> 00:00:06.577 a place known for having some of the most awe-inspiring 00:00:06.601 --> 00:00:09.143 natural landscapes on this planet. 00:00:09.167 --> 00:00:12.624 It's easy to be overwhelmed by these amazing views, 00:00:12.648 --> 00:00:16.513 and to be really fascinated by these sometimes alien-looking formations. 00:00:16.537 --> 00:00:20.195 As a scientist, I love observing the natural world. 00:00:20.219 --> 00:00:21.973 But as a cell biologist, 00:00:21.997 --> 00:00:24.791 I'm much more interested in understanding the natural world 00:00:24.815 --> 00:00:27.077 at a much, much smaller scale. NOTE Paragraph 00:00:27.934 --> 00:00:30.713 I'm a molecular animator, and I work with other researchers 00:00:30.737 --> 00:00:33.633 to create visualizations of molecules that are so small, 00:00:33.657 --> 00:00:35.252 they're essentially invisible. 00:00:35.276 --> 00:00:38.138 These molecules are smaller than the wavelength of light, 00:00:38.162 --> 00:00:40.407 which means that we can never see them directly, 00:00:40.431 --> 00:00:42.495 even with the best light microscopes. 00:00:42.519 --> 00:00:44.645 So do I create visualizations of things 00:00:44.669 --> 00:00:46.641 that are so small we can't see them? NOTE Paragraph 00:00:46.665 --> 00:00:48.823 Scientists, like my collaborators, 00:00:48.847 --> 00:00:50.926 can spend their entire professional careers 00:00:50.950 --> 00:00:53.522 working to understand one molecular process. 00:00:53.546 --> 00:00:56.014 To do this, they carry out a series of experiments 00:00:56.038 --> 00:00:59.141 that each can tell us a small piece of the puzzle. 00:00:59.165 --> 00:01:01.953 One kind of experiment can tell us about the protein shape, 00:01:01.977 --> 00:01:03.188 while another can tell us 00:01:03.204 --> 00:01:05.505 about what other proteins it might interact with 00:01:05.529 --> 00:01:08.441 and another can tell us about where it can be found in a cell. 00:01:08.465 --> 00:01:12.474 And all of these bits of information can be used to come up with a hypothesis, 00:01:12.498 --> 00:01:15.595 a story, essentially, of how a molecule might work. NOTE Paragraph 00:01:16.990 --> 00:01:20.948 My job is to take these ideas and turn them into an animation. 00:01:20.972 --> 00:01:22.155 This can be tricky, 00:01:22.179 --> 00:01:25.488 because it turns out that molecules can do some pretty crazy things. 00:01:25.512 --> 00:01:28.837 But these animations can be incredibly useful for researchers 00:01:28.861 --> 00:01:31.657 to communicate their ideas of how these molecules work. 00:01:32.020 --> 00:01:34.766 They can also allow us to see the molecular world 00:01:34.790 --> 00:01:36.057 through their eyes. NOTE Paragraph 00:01:36.377 --> 00:01:38.297 I'd like to show you some animations, 00:01:38.321 --> 00:01:41.871 a brief tour of what I consider to be some of the natural wonders 00:01:41.895 --> 00:01:43.569 of the molecular world. 00:01:43.593 --> 00:01:45.561 First off, this is an immune cell. 00:01:45.585 --> 00:01:48.458 These kinds of cells need to go crawling around in our bodies 00:01:48.482 --> 00:01:51.537 in order to find invaders like pathogenic bacteria. 00:01:51.561 --> 00:01:54.649 This movement is powered by one of my favorite proteins 00:01:54.673 --> 00:01:55.839 called actin, 00:01:55.863 --> 00:01:58.426 which is part of what's known as the cytoskeleton. 00:01:58.450 --> 00:02:00.085 Unlike our skeletons, 00:02:00.109 --> 00:02:03.847 actin filaments are constantly being built and taken apart. 00:02:03.871 --> 00:02:07.268 The actin cytoskeleton plays incredibly important roles in our cells. 00:02:07.292 --> 00:02:09.054 They allow them to change shape, 00:02:09.078 --> 00:02:11.466 to move around, to adhere to surfaces, 00:02:11.490 --> 00:02:13.926 and also to gobble up bacteria. NOTE Paragraph 00:02:13.950 --> 00:02:16.569 Actin is also involved in a different kind of movement. 00:02:16.593 --> 00:02:19.776 In our muscle cells, actin structures form these regular filaments 00:02:19.800 --> 00:02:21.323 that look kind of like fabric. 00:02:21.347 --> 00:02:24.257 When our muscles contract, these filaments are pulled together 00:02:24.281 --> 00:02:26.297 and they go back to their original position 00:02:26.321 --> 00:02:27.823 when our muscles relax. NOTE Paragraph 00:02:27.847 --> 00:02:31.049 Other parts of the cytoskeleton, in this case microtubules, 00:02:31.073 --> 00:02:33.779 are responsible for long-range transportation. 00:02:33.803 --> 00:02:36.422 They can be thought of as basically cellular highways 00:02:36.446 --> 00:02:39.795 that are used to move things from one side of the cell to the other. 00:02:39.819 --> 00:02:42.607 Unlike our roads, microtubules grow and shrink, 00:02:42.631 --> 00:02:44.052 appearing when they're needed 00:02:44.076 --> 00:02:46.449 and disappearing when their job is done. NOTE Paragraph 00:02:46.473 --> 00:02:48.893 The molecular version of semitrucks 00:02:48.917 --> 00:02:51.474 are proteins aptly named motor proteins, 00:02:51.498 --> 00:02:53.958 that can walk along microtubules, 00:02:53.982 --> 00:02:56.680 dragging sometimes huge cargoes, 00:02:56.704 --> 00:02:58.514 like organelles, behind them. 00:02:58.538 --> 00:03:01.410 This particular motor protein is known as dynein, 00:03:01.434 --> 00:03:03.836 and its known to be able to work together in groups 00:03:03.860 --> 00:03:07.315 that almost look, at least to me, like a chariot of horses. NOTE Paragraph 00:03:07.339 --> 00:03:11.172 As you see, the cell is this incredibly changing, dynamic place, 00:03:11.196 --> 00:03:14.323 where things are constantly being built and disassembled. 00:03:14.680 --> 00:03:16.029 But some of these structures 00:03:16.053 --> 00:03:18.156 are harder to take apart than others, though. 00:03:18.180 --> 00:03:20.093 And special forces need to be brought in 00:03:20.117 --> 00:03:23.562 in order to make sure that structures are taken apart in a timely manner. 00:03:23.586 --> 00:03:26.305 That job is done in part by proteins like these. 00:03:26.329 --> 00:03:27.860 These donut-shaped proteins, 00:03:27.884 --> 00:03:29.892 of which there are many types in the cell, 00:03:29.916 --> 00:03:31.995 all seem to act to rip apart structures 00:03:32.019 --> 00:03:35.384 by basically pulling individual proteins through a central hole. 00:03:35.408 --> 00:03:37.965 When these kinds of proteins don't work properly, 00:03:37.989 --> 00:03:40.719 the types of proteins that are supposed to get taken apart 00:03:40.743 --> 00:03:43.180 can sometimes stick together and aggregate 00:03:43.204 --> 00:03:47.084 and that can give rise to terrible diseases, such as Alzheimer. NOTE Paragraph 00:03:47.419 --> 00:03:49.426 And now let's take a look at the nucleus, 00:03:49.450 --> 00:03:52.403 which houses our genome in the form of DNA. 00:03:52.427 --> 00:03:53.847 In all of our cells, 00:03:53.871 --> 00:03:58.164 our DNA is cared for and maintained by a diverse set of proteins. 00:03:58.188 --> 00:04:01.006 DNA is wound around proteins called histones, 00:04:01.030 --> 00:04:05.338 which enable cells to pack large amounts of DNA into our nucleus. 00:04:05.362 --> 00:04:08.441 These machines are called chromatin remodelers 00:04:08.465 --> 00:04:11.203 and the way they work is that they basically scoot the DNA 00:04:11.227 --> 00:04:12.426 around these histones 00:04:12.450 --> 00:04:16.347 and they allow new pieces of DNA to become exposed. 00:04:16.371 --> 00:04:19.307 This DNA can then be recognized by other machinery. 00:04:19.331 --> 00:04:21.856 In this case, this large molecular machine 00:04:21.880 --> 00:04:23.570 is looking for a segment of DNA 00:04:23.594 --> 00:04:25.903 that tells it it's at the beginning of a gene. 00:04:25.927 --> 00:04:27.616 Once it finds a segment, 00:04:27.640 --> 00:04:30.402 it basically undergoes a series of shape changes 00:04:30.426 --> 00:04:32.528 which enables it to bring in other machinery 00:04:32.552 --> 00:04:36.242 that in turn allows a gene to get turned on or transcribed. 00:04:36.704 --> 00:04:39.791 This has to be a very tightly regulated process 00:04:39.815 --> 00:04:42.617 because turning on the wrong gene at the wrong time 00:04:42.641 --> 00:04:45.283 can have disastrous consequences. NOTE Paragraph 00:04:45.307 --> 00:04:48.117 Scientists are now able to use protein machines 00:04:48.141 --> 00:04:49.545 to edit genomes. 00:04:49.569 --> 00:04:52.013 I'm sure all of you have heard of CRISPR. 00:04:52.037 --> 00:04:54.863 CRISPR takes advantage of a protein known as Cas9, 00:04:54.887 --> 00:04:57.823 which can be engineered to recognize and cut 00:04:57.847 --> 00:05:00.212 a very specific sequence of DNA. 00:05:00.236 --> 00:05:01.395 In this example, 00:05:01.419 --> 00:05:05.514 two Cas9 proteins are being used to excise a problematic piece of DNA. 00:05:05.538 --> 00:05:09.019 For example, a part of a gene that may give rise to a disease. 00:05:09.043 --> 00:05:10.530 Cellular machinery is then used 00:05:10.554 --> 00:05:14.067 to basically glue two ends of the DNA back together. NOTE Paragraph 00:05:14.091 --> 00:05:15.337 As a molecular animator, 00:05:15.361 --> 00:05:18.383 one of my biggest challenges is visualizing uncertainty. 00:05:18.720 --> 00:05:22.029 All of the animations I've shown to you represent hypotheses, 00:05:22.053 --> 00:05:24.294 how my collaborators think a process works, 00:05:24.318 --> 00:05:26.680 based on the best information that they have. 00:05:26.704 --> 00:05:28.672 But for a lot of molecular processes, 00:05:28.696 --> 00:05:31.672 we're still really at the early stages of understanding things, 00:05:31.696 --> 00:05:33.038 and there's a lot to learn. 00:05:33.062 --> 00:05:34.212 The truth is, 00:05:34.236 --> 00:05:38.767 that these invisible molecular worlds are vast and largely unexplored. 00:05:39.474 --> 00:05:41.508 To me, these molecular landscapes 00:05:41.532 --> 00:05:44.926 are just as exciting to explore as a natural world 00:05:44.950 --> 00:05:46.883 that's visible all around us. NOTE Paragraph 00:05:47.379 --> 00:05:48.530 Thank you. NOTE Paragraph 00:05:48.554 --> 00:05:51.760 (Applause)