WEBVTT 00:00:02.417 --> 00:00:03.684 I live in Utah, 00:00:03.708 --> 00:00:06.559 a place known for having some of the most awe-inspiring 00:00:06.583 --> 00:00:09.143 natural landscapes on this planet. 00:00:09.167 --> 00:00:12.643 It's easy to be overwhelmed by these amazing views, 00:00:12.667 --> 00:00:16.518 and to be really fascinated by these sometimes alien-looking formations. 00:00:16.542 --> 00:00:20.184 As a scientist, I love observing the natural world. 00:00:20.208 --> 00:00:21.976 But as a cell biologist, 00:00:22.000 --> 00:00:24.809 I'm much more interested in understanding the natural world 00:00:24.833 --> 00:00:27.042 at a much, much smaller scale. NOTE Paragraph 00:00:27.917 --> 00:00:30.726 I'm a molecular animator, and I work with other researchers 00:00:30.750 --> 00:00:33.643 to create visualizations of molecules that are so small, 00:00:33.667 --> 00:00:35.268 they're essentially invisible. 00:00:35.292 --> 00:00:38.143 These molecules are smaller than the wavelength of light, 00:00:38.167 --> 00:00:40.406 which means that we can never see them directly, 00:00:40.430 --> 00:00:42.476 even with the best light microscopes. 00:00:42.500 --> 00:00:44.643 So how do I create visualizations of things 00:00:44.667 --> 00:00:46.643 that are so small we can't see them? NOTE Paragraph 00:00:46.667 --> 00:00:48.809 Scientists, like my collaborators, 00:00:48.833 --> 00:00:50.934 can spend their entire professional careers 00:00:50.958 --> 00:00:53.518 working to understand one molecular process. 00:00:53.542 --> 00:00:56.018 To do this, they carry out a series of experiments 00:00:56.042 --> 00:00:59.143 that each can tell us a small piece of the puzzle. 00:00:59.167 --> 00:01:01.934 One kind of experiment can tell us about the protein shape, 00:01:01.958 --> 00:01:03.226 while another can tell us 00:01:03.250 --> 00:01:05.536 about what other proteins it might interact with, 00:01:05.560 --> 00:01:08.465 and another can tell us about where it can be found in a cell. 00:01:08.489 --> 00:01:12.476 And all of these bits of information can be used to come up with a hypothesis, 00:01:12.500 --> 00:01:15.583 a story, essentially, of how a molecule might work. NOTE Paragraph 00:01:17.000 --> 00:01:20.934 My job is to take these ideas and turn them into an animation. 00:01:20.958 --> 00:01:22.226 This can be tricky, 00:01:22.250 --> 00:01:25.476 because it turns out that molecules can do some pretty crazy things. 00:01:25.500 --> 00:01:28.851 But these animations can be incredibly useful for researchers 00:01:28.875 --> 00:01:31.976 to communicate their ideas of how these molecules work. 00:01:32.000 --> 00:01:34.768 They can also allow us to see the molecular world 00:01:34.792 --> 00:01:36.351 through their eyes. NOTE Paragraph 00:01:36.375 --> 00:01:38.309 I'd like to show you some animations, 00:01:38.333 --> 00:01:41.851 a brief tour of what I consider to be some of the natural wonders 00:01:41.875 --> 00:01:43.559 of the molecular world. 00:01:43.583 --> 00:01:45.559 First off, this is an immune cell. 00:01:45.583 --> 00:01:48.476 These kinds of cells need to go crawling around in our bodies 00:01:48.500 --> 00:01:51.518 in order to find invaders like pathogenic bacteria. 00:01:51.542 --> 00:01:54.643 This movement is powered by one of my favorite proteins 00:01:54.667 --> 00:01:55.934 called actin, 00:01:55.958 --> 00:01:58.434 which is part of what's known as the cytoskeleton. 00:01:58.458 --> 00:02:00.101 Unlike our skeletons, 00:02:00.125 --> 00:02:03.851 actin filaments are constantly being built and taken apart. 00:02:03.875 --> 00:02:07.268 The actin cytoskeleton plays incredibly important roles in our cells. 00:02:07.292 --> 00:02:09.059 They allow them to change shape, 00:02:09.083 --> 00:02:11.476 to move around, to adhere to surfaces 00:02:11.500 --> 00:02:13.934 and also to gobble up bacteria. NOTE Paragraph 00:02:13.958 --> 00:02:16.559 Actin is also involved in a different kind of movement. 00:02:16.583 --> 00:02:19.768 In our muscle cells, actin structures form these regular filaments 00:02:19.792 --> 00:02:21.309 that look kind of like fabric. 00:02:21.333 --> 00:02:24.268 When our muscles contract, these filaments are pulled together 00:02:24.292 --> 00:02:26.309 and they go back to their original position 00:02:26.333 --> 00:02:27.809 when our muscles relax. NOTE Paragraph 00:02:27.833 --> 00:02:31.059 Other parts of the cytoskeleton, in this case microtubules, 00:02:31.083 --> 00:02:33.768 are responsible for long-range transportation. 00:02:33.792 --> 00:02:36.434 They can be thought of as basically cellular highways 00:02:36.458 --> 00:02:39.809 that are used to move things from one side of the cell to the other. 00:02:39.833 --> 00:02:42.601 Unlike our roads, microtubules grow and shrink, 00:02:42.625 --> 00:02:44.059 appearing when they're needed 00:02:44.083 --> 00:02:46.434 and disappearing when their job is done. NOTE Paragraph 00:02:46.458 --> 00:02:48.893 The molecular version of semitrucks 00:02:48.917 --> 00:02:51.476 are proteins aptly named motor proteins, 00:02:51.500 --> 00:02:53.976 that can walk along microtubules, 00:02:54.000 --> 00:02:56.684 dragging sometimes huge cargoes, 00:02:56.708 --> 00:02:58.518 like organelles, behind them. 00:02:58.542 --> 00:03:01.393 This particular motor protein is known as dynein, 00:03:01.417 --> 00:03:03.851 and its known to be able to work together in groups 00:03:03.875 --> 00:03:07.309 that almost look, at least to me, like a chariot of horses. NOTE Paragraph 00:03:07.333 --> 00:03:11.184 As you see, the cell is this incredibly changing, dynamic place, 00:03:11.208 --> 00:03:14.643 where things are constantly being built and disassembled. 00:03:14.667 --> 00:03:16.018 But some of these structures 00:03:16.042 --> 00:03:18.143 are harder to take apart than others, though. 00:03:18.167 --> 00:03:20.101 And special forces need to be brought in 00:03:20.125 --> 00:03:23.559 in order to make sure that structures are taken apart in a timely manner. 00:03:23.583 --> 00:03:26.309 That job is done in part by proteins like these. 00:03:26.333 --> 00:03:27.851 These donut-shaped proteins, 00:03:27.875 --> 00:03:29.893 of which there are many types in the cell, 00:03:29.917 --> 00:03:31.976 all seem to act to rip apart structures 00:03:32.000 --> 00:03:35.393 by basically pulling individual proteins through a central hole. 00:03:35.417 --> 00:03:37.976 When these kinds of proteins don't work properly, 00:03:38.000 --> 00:03:40.726 the types of proteins that are supposed to get taken apart 00:03:40.750 --> 00:03:43.184 can sometimes stick together and aggregate 00:03:43.208 --> 00:03:47.393 and that can give rise to terrible diseases, such as Alzheimer's. NOTE Paragraph 00:03:47.417 --> 00:03:49.434 And now let's take a look at the nucleus, 00:03:49.458 --> 00:03:52.393 which houses our genome in the form of DNA. 00:03:52.417 --> 00:03:53.851 In all of our cells, 00:03:53.875 --> 00:03:58.184 our DNA is cared for and maintained by a diverse set of proteins. 00:03:58.208 --> 00:04:01.018 DNA is wound around proteins called histones, 00:04:01.042 --> 00:04:05.351 which enable cells to pack large amounts of DNA into our nucleus. 00:04:05.375 --> 00:04:08.434 These machines are called chromatin remodelers, 00:04:08.458 --> 00:04:11.184 and the way they work is that they basically scoot the DNA 00:04:11.208 --> 00:04:12.476 around these histones 00:04:12.500 --> 00:04:16.351 and they allow new pieces of DNA to become exposed. 00:04:16.375 --> 00:04:19.309 This DNA can then be recognized by other machinery. 00:04:19.333 --> 00:04:21.851 In this case, this large molecular machine 00:04:21.875 --> 00:04:23.559 is looking for a segment of DNA 00:04:23.583 --> 00:04:25.893 that tells it it's at the beginning of a gene. 00:04:25.917 --> 00:04:27.601 Once it finds a segment, 00:04:27.625 --> 00:04:30.393 it basically undergoes a series of shape changes 00:04:30.417 --> 00:04:32.518 which enables it to bring in other machinery 00:04:32.542 --> 00:04:36.684 that in turn allows a gene to get turned on or transcribed. 00:04:36.708 --> 00:04:39.809 This has to be a very tightly regulated process, 00:04:39.833 --> 00:04:42.601 because turning on the wrong gene at the wrong time 00:04:42.625 --> 00:04:45.268 can have disastrous consequences. NOTE Paragraph 00:04:45.292 --> 00:04:48.101 Scientists are now able to use protein machines 00:04:48.125 --> 00:04:49.559 to edit genomes. 00:04:49.583 --> 00:04:52.018 I'm sure all of you have heard of CRISPR. 00:04:52.042 --> 00:04:54.851 CRISPR takes advantage of a protein known as Cas9, 00:04:54.875 --> 00:04:57.809 which can be engineered to recognize and cut 00:04:57.833 --> 00:05:00.226 a very specific sequence of DNA. 00:05:00.250 --> 00:05:01.518 In this example, 00:05:01.542 --> 00:05:05.518 two Cas9 proteins are being used to excise a problematic piece of DNA. 00:05:05.542 --> 00:05:09.018 For example, a part of a gene that may give rise to a disease. 00:05:09.042 --> 00:05:10.519 Cellular machinery is then used 00:05:10.543 --> 00:05:14.059 to basically glue two ends of the DNA back together. NOTE Paragraph 00:05:14.083 --> 00:05:15.351 As a molecular animator, 00:05:15.375 --> 00:05:18.684 one of my biggest challenges is visualizing uncertainty. 00:05:18.708 --> 00:05:22.018 All of the animations I've shown to you represent hypotheses, 00:05:22.042 --> 00:05:24.309 how my collaborators think a process works, 00:05:24.333 --> 00:05:26.684 based on the best information that they have. 00:05:26.708 --> 00:05:28.684 But for a lot of molecular processes, 00:05:28.708 --> 00:05:31.684 we're still really at the early stages of understanding things, 00:05:31.708 --> 00:05:33.018 and there's a lot to learn. 00:05:33.042 --> 00:05:34.309 The truth is 00:05:34.333 --> 00:05:38.292 that these invisible molecular worlds are vast and largely unexplored. 00:05:39.458 --> 00:05:41.518 To me, these molecular landscapes 00:05:41.542 --> 00:05:44.934 are just as exciting to explore as a natural world 00:05:44.958 --> 00:05:47.351 that's visible all around us. NOTE Paragraph 00:05:47.375 --> 00:05:48.643 Thank you. NOTE Paragraph 00:05:48.667 --> 00:05:51.792 (Applause)