So good afternoon everybody and welcome to this inaugural lecture. 9580b482-17f5-4151-b80b-bf83c7deef23/135-1 00:20:21.502 --> 00:20:26.569 It's a pleasure to be hosting this lecture here today for for Karuna. 9580b482-17f5-4151-b80b-bf83c7deef23/135-2 00:20:26.569 --> 00:20:31.202 For people I've had the opportunity to meet, I'm Gavin Perkins, 9580b482-17f5-4151-b80b-bf83c7deef23/135-3 00:20:31.202 --> 00:20:33.012 I'm the Dean of Medicine. 9580b482-17f5-4151-b80b-bf83c7deef23/137-0 00:20:33.092 --> 00:20:38.319 Here at 糖心TV and it really is a fantastic opportunity for celebration. 9580b482-17f5-4151-b80b-bf83c7deef23/137-1 00:20:38.319 --> 00:20:42.416 Professor Karina Sampath, family, friends and colleagues, 9580b482-17f5-4151-b80b-bf83c7deef23/137-2 00:20:42.416 --> 00:20:47.290 welcome to this inaugural lecture. The inaugural lecture is actually 9580b482-17f5-4151-b80b-bf83c7deef23/137-3 00:20:47.290 --> 00:20:52.164 something really important, especially represents a key milestone in 9580b482-17f5-4151-b80b-bf83c7deef23/137-4 00:20:52.164 --> 00:20:53.012 an academic. 9580b482-17f5-4151-b80b-bf83c7deef23/139-0 00:20:53.012 --> 00:20:56.801 Career signifying their promotion to professor. 9580b482-17f5-4151-b80b-bf83c7deef23/139-1 00:20:56.801 --> 00:21:03.196 And that promotion to professor is more because it's not just a change in style. 9580b482-17f5-4151-b80b-bf83c7deef23/139-2 00:21:03.196 --> 00:21:06.669 It's not something that's bestowed lightly. 9580b482-17f5-4151-b80b-bf83c7deef23/139-3 00:21:06.669 --> 00:21:10.932 It's a meticulous process of assessment that someone. 9580b482-17f5-4151-b80b-bf83c7deef23/140-0 00:21:10.932 --> 00:21:16.776 Is assessed with their their peers, and it's a profound marker of the respect 9580b482-17f5-4151-b80b-bf83c7deef23/140-1 00:21:16.776 --> 00:21:22.770 and admiration that people have through the mistake of the title of assessment, 9580b482-17f5-4151-b80b-bf83c7deef23/140-2 00:21:22.770 --> 00:21:25.692 which is a truly exceptional colleague. 9580b482-17f5-4151-b80b-bf83c7deef23/141-0 00:21:26.132 --> 00:21:31.801 This honour acknowledges your remarkable contributions and the valuable impact you 9580b482-17f5-4151-b80b-bf83c7deef23/141-1 00:21:31.801 --> 00:21:36.582 have not only in your field, but also to the broader higher education 9580b482-17f5-4151-b80b-bf83c7deef23/141-2 00:21:36.582 --> 00:21:39.792 sector. It also sets high expectations for the 9580b482-17f5-4151-b80b-bf83c7deef23/141-3 00:21:39.792 --> 00:21:43.412 future contributions holding the title of Professor. 9580b482-17f5-4151-b80b-bf83c7deef23/142-0 00:21:43.492 --> 00:21:48.236 It implies the responsibility to uphold and champion the principles of 9580b482-17f5-4151-b80b-bf83c7deef23/142-1 00:21:48.236 --> 00:21:53.046 collegiality, academic freedom, and the relentless pursuit of knowledge 9580b482-17f5-4151-b80b-bf83c7deef23/142-2 00:21:53.046 --> 00:21:55.986 and practice for the betterment of society. 9580b482-17f5-4151-b80b-bf83c7deef23/142-3 00:21:55.986 --> 00:22:00.997 We're incredibly fortunate to have Professor Grudius Sampath as one of our 9580b482-17f5-4151-b80b-bf83c7deef23/142-4 00:22:00.997 --> 00:22:01.732 colleagues. 9580b482-17f5-4151-b80b-bf83c7deef23/144-0 00:22:02.212 --> 00:22:07.146 Her pioneering work over the last 30 years on the fundamental mechanisms that 9580b482-17f5-4151-b80b-bf83c7deef23/144-1 00:22:07.146 --> 00:22:12.080 control development and differentiation has seen her work around the world of 9580b482-17f5-4151-b80b-bf83c7deef23/144-2 00:22:12.080 --> 00:22:16.317 price making 糖心TV a home in 2014, your awakening dedication and 9580b482-17f5-4151-b80b-bf83c7deef23/144-3 00:22:16.317 --> 00:22:20.492 achievements of service as an inspiration to the wider community. 9580b482-17f5-4151-b80b-bf83c7deef23/146-0 00:22:20.772 --> 00:22:25.888 This honour acknowledges your remarkable achievements and the valuable impact that 9580b482-17f5-4151-b80b-bf83c7deef23/146-1 00:22:25.888 --> 00:22:30.573 you made on your field at the border landscape in higher education. Bruner, 9580b482-17f5-4151-b80b-bf83c7deef23/146-2 00:22:30.573 --> 00:22:35.504 please share where is your noble lecture. How does an egg know where to put the 9580b482-17f5-4151-b80b-bf83c7deef23/146-3 00:22:35.504 --> 00:22:35.812 head? 9580b482-17f5-4151-b80b-bf83c7deef23/147-0 00:22:35.812 --> 00:22:36.492 Thank you, Kevin. 9580b482-17f5-4151-b80b-bf83c7deef23/148-0 00:22:38.372 --> 00:22:43.532 Thank you all for coming today. And to everyone who's online, 9580b482-17f5-4151-b80b-bf83c7deef23/148-1 00:22:43.532 --> 00:22:47.361 thank you very much for joining this lecture. 9580b482-17f5-4151-b80b-bf83c7deef23/148-2 00:22:47.361 --> 00:22:53.769 I have posted this a couple of times, so in in all fairness, it's, you know, 9580b482-17f5-4151-b80b-bf83c7deef23/148-3 00:22:53.769 --> 00:22:56.932 it's my fault this is happening today. 9580b482-17f5-4151-b80b-bf83c7deef23/149-0 00:22:57.252 --> 00:23:02.228 But thank you all the same. So I was told that this talk is more 9580b482-17f5-4151-b80b-bf83c7deef23/149-1 00:23:02.228 --> 00:23:06.667 about, you know, the journey and how I got to where I am. 9580b482-17f5-4151-b80b-bf83c7deef23/149-2 00:23:06.667 --> 00:23:11.490 So there'll be a little bit of science and a lot of, you know, 9580b482-17f5-4151-b80b-bf83c7deef23/149-3 00:23:11.490 --> 00:23:14.092 how things came about and and how. 9580b482-17f5-4151-b80b-bf83c7deef23/150-0 00:23:14.932 --> 00:23:19.333 We are where we are today. So I've been interested in in the 9580b482-17f5-4151-b80b-bf83c7deef23/150-1 00:23:19.333 --> 00:23:23.590 fundamental mechanisms that make the vertebrate body plan. 9580b482-17f5-4151-b80b-bf83c7deef23/150-2 00:23:23.590 --> 00:23:29.290 And we care about this because 6% of all newborns globally have a birth defect 9580b482-17f5-4151-b80b-bf83c7deef23/150-3 00:23:29.290 --> 00:23:34.412 when they're born and we still don't fully understand what goes wrong. 9580b482-17f5-4151-b80b-bf83c7deef23/151-0 00:23:37.052 --> 00:23:37.532 OK. 9580b482-17f5-4151-b80b-bf83c7deef23/152-0 00:23:40.452 --> 00:23:50.132 They didn't mind not hearing me. So I'm here. Can you go to that? 9580b482-17f5-4151-b80b-bf83c7deef23/153-0 00:23:51.812 --> 00:23:56.634 Go back back on. Where's IT when you need them? 9580b482-17f5-4151-b80b-bf83c7deef23/153-1 00:23:56.634 --> 00:24:02.662 Could you go to that pop out there? Is that on your laptop? 9580b482-17f5-4151-b80b-bf83c7deef23/153-2 00:24:02.662 --> 00:24:04.972 Can you hit it on that? 9580b482-17f5-4151-b80b-bf83c7deef23/154-0 00:24:09.772 --> 00:24:12.292 Oops, there was a little pop up there. 9580b482-17f5-4151-b80b-bf83c7deef23/155-0 00:24:17.652 --> 00:24:19.332 I don't know what's happening. 9580b482-17f5-4151-b80b-bf83c7deef23/157-0 00:24:21.812 --> 00:24:26.656 I think it was on teams. If you go back onto because look, 9580b482-17f5-4151-b80b-bf83c7deef23/157-1 00:24:26.656 --> 00:24:29.612 I hear this one the the lights logo. 9580b482-17f5-4151-b80b-bf83c7deef23/158-0 00:24:30.612 --> 00:24:37.336 Can you hear me now? Yeah. OK. All right. Very good. OK. No, 9580b482-17f5-4151-b80b-bf83c7deef23/159-0 00:24:30.732 --> 00:24:37.835 Can you hear me now? Yeah. OK. All right. Very good. Can we turn that one off then, 9580b482-17f5-4151-b80b-bf83c7deef23/158-1 00:24:37.336 --> 00:24:40.092 I didn't need to hear me. 9580b482-17f5-4151-b80b-bf83c7deef23/159-1 00:24:37.835 --> 00:24:41.132 because I think they could hear before. 9580b482-17f5-4151-b80b-bf83c7deef23/161-0 00:24:43.292 --> 00:24:46.252 This one. Can you hear me now? 9580b482-17f5-4151-b80b-bf83c7deef23/160-0 00:24:43.692 --> 00:24:43.972 This one. 9580b482-17f5-4151-b80b-bf83c7deef23/162-0 00:24:52.252 --> 00:24:56.752 Yes. OK. OK, very good. I'll just hold on this. 9580b482-17f5-4151-b80b-bf83c7deef23/162-1 00:24:56.752 --> 00:25:01.252 I might minimize that and I'll go back to this. 9580b482-17f5-4151-b80b-bf83c7deef23/163-0 00:25:03.772 --> 00:25:07.765 All right, so clearly about 6% of all newborns have 9580b482-17f5-4151-b80b-bf83c7deef23/163-1 00:25:07.765 --> 00:25:12.602 a birth defect and we don't really understand what goes wrong. 9580b482-17f5-4151-b80b-bf83c7deef23/163-2 00:25:12.602 --> 00:25:17.133 And within the UK, about one in every 43 children that are 9580b482-17f5-4151-b80b-bf83c7deef23/163-3 00:25:17.133 --> 00:25:19.052 born have a birth defect. 9580b482-17f5-4151-b80b-bf83c7deef23/164-0 00:25:19.452 --> 00:25:24.441 And so that's about 235 per 10,000 births, of which of the 235, 9580b482-17f5-4151-b80b-bf83c7deef23/164-1 00:25:24.441 --> 00:25:29.819 67 actually have heart defects. And I'll come back to this later on. 9580b482-17f5-4151-b80b-bf83c7deef23/164-2 00:25:29.819 --> 00:25:35.197 So why should we study a fish at all? And we've been using the fish, 9580b482-17f5-4151-b80b-bf83c7deef23/164-3 00:25:35.197 --> 00:25:39.172 the zebra fish as the primary experimental system. 9580b482-17f5-4151-b80b-bf83c7deef23/165-0 00:25:39.252 --> 00:25:43.356 to understand the basis of how the body plan gets made. 9580b482-17f5-4151-b80b-bf83c7deef23/165-1 00:25:43.356 --> 00:25:47.533 And here's the the beautiful zebrafish shown here below. 9580b482-17f5-4151-b80b-bf83c7deef23/165-2 00:25:47.533 --> 00:25:52.297 It's a small tropical fish. It actually goes in fresh waters all 9580b482-17f5-4151-b80b-bf83c7deef23/165-3 00:25:52.297 --> 00:25:58.086 across Asia and Southeast Asia from the foothills of the Himalayas all the way 9580b482-17f5-4151-b80b-bf83c7deef23/165-4 00:25:58.086 --> 00:25:58.892 through the 9580b482-17f5-4151-b80b-bf83c7deef23/167-0 00:25:59.172 --> 00:26:04.496 the Malayan Straits and and Southeast Asia, Singapore, Indonesia, 9580b482-17f5-4151-b80b-bf83c7deef23/167-1 00:26:04.496 --> 00:26:10.303 everywhere you can find this. And the reason this was picked up as a as 9580b482-17f5-4151-b80b-bf83c7deef23/167-2 00:26:10.303 --> 00:26:15.062 a model of organism is because of its share, surprisingly, 9580b482-17f5-4151-b80b-bf83c7deef23/167-3 00:26:15.062 --> 00:26:18.772 it shares 84% of the human disease genes have 9580b482-17f5-4151-b80b-bf83c7deef23/168-0 00:26:18.772 --> 00:26:22.996 Counterpart in Fish, the sequence, the genome sequence was done by the 9580b482-17f5-4151-b80b-bf83c7deef23/168-1 00:26:22.996 --> 00:26:27.637 Welcome to Sander Center and and and and they found that 84% of human disease 9580b482-17f5-4151-b80b-bf83c7deef23/168-2 00:26:27.637 --> 00:26:32.575 genes, even though we look so different, we actually share so many genes in common 9580b482-17f5-4151-b80b-bf83c7deef23/168-3 00:26:32.575 --> 00:26:35.848 and the it's a simple word. It goes extremely quickly, 9580b482-17f5-4151-b80b-bf83c7deef23/168-4 00:26:35.848 --> 00:26:37.692 so from the time of conception. 9580b482-17f5-4151-b80b-bf83c7deef23/169-0 00:26:37.892 --> 00:26:41.711 to uh when the heart beats is only 32 hours, okay. 9580b482-17f5-4151-b80b-bf83c7deef23/169-1 00:26:41.711 --> 00:26:47.553 So a day after the egg is fertilized by the sperm, you have a beaching heart, 9580b482-17f5-4151-b80b-bf83c7deef23/169-2 00:26:47.553 --> 00:26:52.720 you have a circulatory system, you have the rudiments of most of the 9580b482-17f5-4151-b80b-bf83c7deef23/169-3 00:26:52.720 --> 00:26:57.812 major organs. And this allows us, and and all this happens outside, 9580b482-17f5-4151-b80b-bf83c7deef23/170-0 00:26:57.892 --> 00:27:01.107 the water, and you can take a single cell solution 9580b482-17f5-4151-b80b-bf83c7deef23/170-1 00:27:01.107 --> 00:27:05.078 and keep these eggs, and you can observe how these tissues and 9580b482-17f5-4151-b80b-bf83c7deef23/170-2 00:27:05.078 --> 00:27:09.050 organs come together, and you can also manipulate them in many 9580b482-17f5-4151-b80b-bf83c7deef23/170-3 00:27:09.050 --> 00:27:11.761 ways. There have been genetic screens done 9580b482-17f5-4151-b80b-bf83c7deef23/170-4 00:27:11.761 --> 00:27:15.354 throughout the world, both through classical approaches, 9580b482-17f5-4151-b80b-bf83c7deef23/170-5 00:27:15.354 --> 00:27:17.812 and more recently through gene editing. 9580b482-17f5-4151-b80b-bf83c7deef23/171-0 00:27:17.892 --> 00:27:23.459 You can also do a lot of other manipulations. You can purify proteins, 9580b482-17f5-4151-b80b-bf83c7deef23/171-1 00:27:23.459 --> 00:27:29.495 you can purify complexes because they produce large numbers of eggs in every 9580b482-17f5-4151-b80b-bf83c7deef23/171-2 00:27:29.495 --> 00:27:34.591 egg lay. And of course, this is also very valuable for for doing 9580b482-17f5-4151-b80b-bf83c7deef23/171-3 00:27:34.591 --> 00:27:37.492 compound pharmaceutical drug screens. 9580b482-17f5-4151-b80b-bf83c7deef23/172-0 00:27:37.652 --> 00:27:44.868 Because you get lots of eggs that you can then test for various therapeutic avenues. 9580b482-17f5-4151-b80b-bf83c7deef23/172-1 00:27:44.868 --> 00:27:49.027 So I I started my early career, my my education. 9580b482-17f5-4151-b80b-bf83c7deef23/172-2 00:27:49.027 --> 00:27:54.630 Early education was in India. We traveled throughout the country. 9580b482-17f5-4151-b80b-bf83c7deef23/172-3 00:27:54.630 --> 00:27:56.412 My dad is here today. 9580b482-17f5-4151-b80b-bf83c7deef23/173-0 00:27:57.332 --> 00:28:02.227 So he worked for an oil company. So I went through about six or seven 9580b482-17f5-4151-b80b-bf83c7deef23/173-1 00:28:02.227 --> 00:28:07.192 different schools by the time I I I completed high school and I did my 9580b482-17f5-4151-b80b-bf83c7deef23/173-2 00:28:07.192 --> 00:28:12.855 undergraduate degree at the University of Delhi in in a women's college and then 9580b482-17f5-4151-b80b-bf83c7deef23/173-3 00:28:12.855 --> 00:28:15.932 did my masters at the University of Baroda. 9580b482-17f5-4151-b80b-bf83c7deef23/174-0 00:28:16.212 --> 00:28:22.795 So this is these are some pictures of of my college and that's my graduating 9580b482-17f5-4151-b80b-bf83c7deef23/174-1 00:28:22.795 --> 00:28:26.557 cohort. And this was in in a very classical 9580b482-17f5-4151-b80b-bf83c7deef23/174-2 00:28:26.557 --> 00:28:31.772 subject, virology, where we actually looked at specimens and 9580b482-17f5-4151-b80b-bf83c7deef23/174-3 00:28:31.772 --> 00:28:36.132 we drew them and and it was really utterly boring. 9580b482-17f5-4151-b80b-bf83c7deef23/175-0 00:28:36.212 --> 00:28:44.612 But then I I I joined the university for my master's degree in in biotechnology 9580b482-17f5-4151-b80b-bf83c7deef23/175-1 00:28:44.612 --> 00:28:52.172 and this is where really I I got interested in in science because we've 9580b482-17f5-4151-b80b-bf83c7deef23/175-2 00:28:52.172 --> 00:28:55.532 had really outstanding lectures. 9580b482-17f5-4151-b80b-bf83c7deef23/176-0 00:28:56.252 --> 00:29:01.704 This is Professor Bharat Chittu, who then went on to establish a genomic 9580b482-17f5-4151-b80b-bf83c7deef23/176-1 00:29:01.704 --> 00:29:05.886 center there. And you might recognize somebody here who 9580b482-17f5-4151-b80b-bf83c7deef23/176-2 00:29:05.886 --> 00:29:09.769 was working as a student in Professor Chittu's lab, 9580b482-17f5-4151-b80b-bf83c7deef23/176-3 00:29:09.769 --> 00:29:13.652 who's become then later on a lifelong collaborator. 9580b482-17f5-4151-b80b-bf83c7deef23/177-0 00:29:14.452 --> 00:29:19.549 So in addition to Professor, we also had many other very inspiring 9580b482-17f5-4151-b80b-bf83c7deef23/177-1 00:29:19.549 --> 00:29:23.505 lecturers, and one of these was Johannes Mandraker, 9580b482-17f5-4151-b80b-bf83c7deef23/177-2 00:29:23.505 --> 00:29:29.135 who had just completed his PhD with K S Krishnan at the Tapa Institute of 9580b482-17f5-4151-b80b-bf83c7deef23/177-3 00:29:29.135 --> 00:29:30.732 Fundamental Research. 9580b482-17f5-4151-b80b-bf83c7deef23/178-0 00:29:31.492 --> 00:29:36.298 He had worked on Drosophila, and about this time there were these 9580b482-17f5-4151-b80b-bf83c7deef23/178-1 00:29:36.298 --> 00:29:42.341 really foundational publications from the groups of Young and Baseline Forhard and 9580b482-17f5-4151-b80b-bf83c7deef23/178-2 00:29:42.341 --> 00:29:47.437 others where the the body plan of the fruit fly was being walked out. 9580b482-17f5-4151-b80b-bf83c7deef23/178-3 00:29:47.437 --> 00:29:50.932 They'd done large scale genetic screens at the. 9580b482-17f5-4151-b80b-bf83c7deef23/179-0 00:29:51.012 --> 00:29:55.098 in Germany, and they were just working out what these 9580b482-17f5-4151-b80b-bf83c7deef23/179-1 00:29:55.098 --> 00:29:59.259 pathways were. And one of these was a very fundamental 9580b482-17f5-4151-b80b-bf83c7deef23/179-2 00:29:59.259 --> 00:30:04.025 and really important piece of work on a protein called Bicoid, 9580b482-17f5-4151-b80b-bf83c7deef23/179-3 00:30:04.025 --> 00:30:09.473 which is deposited at the head, what will become the future head end of 9580b482-17f5-4151-b80b-bf83c7deef23/179-4 00:30:09.473 --> 00:30:10.532 the fruit fly. 9580b482-17f5-4151-b80b-bf83c7deef23/180-0 00:30:10.572 --> 00:30:13.853 And Wolfgang Pieber, who was the student in in Yanni Nies 9580b482-17f5-4151-b80b-bf83c7deef23/180-1 00:30:13.853 --> 00:30:17.303 Langvonhardt's lab, who did this work and took up, you know, 9580b482-17f5-4151-b80b-bf83c7deef23/180-2 00:30:17.303 --> 00:30:21.941 he basically aspirated the cytoplasm from from the egg at one end and put it into 9580b482-17f5-4151-b80b-bf83c7deef23/180-3 00:30:21.941 --> 00:30:25.051 the other end. And this fly now had two heads. I mean, 9580b482-17f5-4151-b80b-bf83c7deef23/180-4 00:30:25.051 --> 00:30:28.671 that was such a crude experiment. And I remember thinking, wow, 9580b482-17f5-4151-b80b-bf83c7deef23/180-5 00:30:28.671 --> 00:30:29.972 I wish I could do that. 9580b482-17f5-4151-b80b-bf83c7deef23/182-0 00:30:30.372 --> 00:30:34.891 And it was really nice to actually meet Wolfgang Wieder later on. 9580b482-17f5-4151-b80b-bf83c7deef23/182-1 00:30:34.891 --> 00:30:40.436 And here he is at the European Zebrafish meeting just a few months back in Paris 9580b482-17f5-4151-b80b-bf83c7deef23/182-2 00:30:40.436 --> 00:30:46.050 when I was telling him how his work had really influenced what he then went on to 9580b482-17f5-4151-b80b-bf83c7deef23/182-3 00:30:46.050 --> 00:30:48.172 to go on to do in in Zebrafish. 9580b482-17f5-4151-b80b-bf83c7deef23/181-0 00:30:46.932 --> 00:30:47.492 The. 9580b482-17f5-4151-b80b-bf83c7deef23/184-0 00:30:48.652 --> 00:30:55.672 So we then I went on to the United States, like many people of my generation, 9580b482-17f5-4151-b80b-bf83c7deef23/184-1 00:30:55.672 --> 00:31:03.142 to do a PhD in in cell and developmental biology. And I worked with Danny Stewart. 9580b482-17f5-4151-b80b-bf83c7deef23/184-2 00:31:03.142 --> 00:31:08.092 He was the first person to actually make a transgenic. 9580b482-17f5-4151-b80b-bf83c7deef23/185-0 00:31:08.372 --> 00:31:13.619 Zebrafish way back in the day when there was no fluorescent reporter, 9580b482-17f5-4151-b80b-bf83c7deef23/183-0 00:31:09.092 --> 00:31:09.732 What's up? 9580b482-17f5-4151-b80b-bf83c7deef23/185-1 00:31:13.619 --> 00:31:19.317 even had not been identified yet. He used current acetyl transferase as the 9580b482-17f5-4151-b80b-bf83c7deef23/185-2 00:31:19.317 --> 00:31:22.915 reporter gene, but he made the first transgenic 9580b482-17f5-4151-b80b-bf83c7deef23/185-3 00:31:22.915 --> 00:31:28.012 zebrafish and in his lab I worked on a new class of homeobox genes. 9580b482-17f5-4151-b80b-bf83c7deef23/187-0 00:31:28.092 --> 00:31:34.041 Called powdery genes and determine their expression pattern during zebrafish 9580b482-17f5-4151-b80b-bf83c7deef23/187-1 00:31:34.041 --> 00:31:38.058 development. And I was introduced to this beautiful 9580b482-17f5-4151-b80b-bf83c7deef23/187-2 00:31:38.058 --> 00:31:44.085 organism zebrafish. Following that, I went to Vanderbilt University and there 9580b482-17f5-4151-b80b-bf83c7deef23/187-3 00:31:44.085 --> 00:31:47.252 I worked with Chris Wright on on on frog. 9580b482-17f5-4151-b80b-bf83c7deef23/188-0 00:31:47.772 --> 00:31:53.700 MBA development and Chris actually was an undergrad in in the School of Life 9580b482-17f5-4151-b80b-bf83c7deef23/188-1 00:31:53.700 --> 00:31:59.474 Sciences at 糖心TV in in the 70s. So my little sweet 糖心TV actually had 9580b482-17f5-4151-b80b-bf83c7deef23/188-2 00:31:59.474 --> 00:32:03.092 had, you know, can be dated back to that time. 9580b482-17f5-4151-b80b-bf83c7deef23/190-0 00:32:03.452 --> 00:32:08.192 So Chris had during his early career worked on Hox genes and vertebrates. 9580b482-17f5-4151-b80b-bf83c7deef23/190-1 00:32:08.192 --> 00:32:11.523 He was a part of the the team of Eddie de Robertis, 9580b482-17f5-4151-b80b-bf83c7deef23/190-2 00:32:11.523 --> 00:32:15.430 who had identified Hox genes in frogs and and other systems. 9580b482-17f5-4151-b80b-bf83c7deef23/190-3 00:32:15.430 --> 00:32:18.312 And he then went on to work on one of these, 9580b482-17f5-4151-b80b-bf83c7deef23/190-4 00:32:18.312 --> 00:32:23.372 the pancreatic duodenal homine box gene and it's real in pancreas development. 9580b482-17f5-4151-b80b-bf83c7deef23/192-0 00:32:23.452 --> 00:32:27.173 But he also had a team of which I was a part of, 9580b482-17f5-4151-b80b-bf83c7deef23/192-1 00:32:27.173 --> 00:32:33.476 which worked on signaling growth factor signals using the fraud as a model system. 9580b482-17f5-4151-b80b-bf83c7deef23/192-2 00:32:33.476 --> 00:32:37.728 Because again, in those days you could get lots of eggs 9580b482-17f5-4151-b80b-bf83c7deef23/192-3 00:32:37.728 --> 00:32:42.892 and you could manipulate them in many different ways and you could. 9580b482-17f5-4151-b80b-bf83c7deef23/195-0 00:32:42.892 --> 00:32:47.775 do fundamental embiological work because the frog is actually quite large, 9580b482-17f5-4151-b80b-bf83c7deef23/195-1 00:32:47.775 --> 00:32:52.787 so you can manipulate them physically, you can cut out chunks of the embryo, 9580b482-17f5-4151-b80b-bf83c7deef23/195-2 00:32:52.787 --> 00:32:57.800 do transplantations, do explant cultures, and so on. Of course, genetically, 9580b482-17f5-4151-b80b-bf83c7deef23/195-3 00:32:57.800 --> 00:33:02.812 it's not as amenable as zebrafish. And so this is Chris and Mike Way, who is 9580b482-17f5-4151-b80b-bf83c7deef23/197-0 00:33:02.892 --> 00:33:06.186 A research assistant in his lab during my time, 9580b482-17f5-4151-b80b-bf83c7deef23/196-0 00:33:05.892 --> 00:33:18.772 Some students then they leave that we all having issues with it. 9580b482-17f5-4151-b80b-bf83c7deef23/197-1 00:33:06.186 --> 00:33:11.744 so I got a chance to to visit them again last year during the 糖心TV Vanderbilt 9580b482-17f5-4151-b80b-bf83c7deef23/197-2 00:33:11.744 --> 00:33:15.587 John Symposium. So that was really very nice to go back 9580b482-17f5-4151-b80b-bf83c7deef23/197-3 00:33:15.587 --> 00:33:19.292 and meet all my former colleagues. So in Chris's lab. 9580b482-17f5-4151-b80b-bf83c7deef23/198-0 00:33:19.372 --> 00:33:23.066 Within a couple of months of my journey in his lab, in fact, 9580b482-17f5-4151-b80b-bf83c7deef23/198-1 00:33:23.066 --> 00:33:26.154 and I remember this was over Thanksgiving weekend, 9580b482-17f5-4151-b80b-bf83c7deef23/198-2 00:33:26.154 --> 00:33:29.000 I found that one of the related group factors, 9580b482-17f5-4151-b80b-bf83c7deef23/198-3 00:33:29.000 --> 00:33:32.331 so this is a transforming growth factor family member. 9580b482-17f5-4151-b80b-bf83c7deef23/198-4 00:33:32.331 --> 00:33:36.812 I found that one of these was expressed in the problem day very early on. 9580b482-17f5-4151-b80b-bf83c7deef23/199-0 00:33:39.852 --> 00:33:43.508 In the left side of the embryo. So this is a frog embryo at about early 9580b482-17f5-4151-b80b-bf83c7deef23/199-1 00:33:43.508 --> 00:33:46.047 neural stages. We're looking at it from the back. 9580b482-17f5-4151-b80b-bf83c7deef23/199-2 00:33:46.047 --> 00:33:49.195 This is the midline. So you can see this is the left and this 9580b482-17f5-4151-b80b-bf83c7deef23/199-3 00:33:49.195 --> 00:33:53.308 is the right side and one of the neural genes was expressed in the left side and 9580b482-17f5-4151-b80b-bf83c7deef23/199-4 00:33:53.308 --> 00:33:57.421 then later on it's found in the in the region very close to where the heart will 9580b482-17f5-4151-b80b-bf83c7deef23/199-5 00:33:57.421 --> 00:33:59.452 develop in frog embryos. So what we did. 9580b482-17f5-4151-b80b-bf83c7deef23/200-0 00:33:59.532 --> 00:34:04.667 Was to take this neuro related gene and then this expressed it in what would be 9580b482-17f5-4151-b80b-bf83c7deef23/200-1 00:34:04.667 --> 00:34:09.545 the future right side of the embryo. And what we were able to do is to then 9580b482-17f5-4151-b80b-bf83c7deef23/200-2 00:34:09.545 --> 00:34:13.203 randomize the positioning of both the heart and the gut. 9580b482-17f5-4151-b80b-bf83c7deef23/200-3 00:34:13.203 --> 00:34:17.953 So normally in all vertebrates, the heart is positioned on the left side. 9580b482-17f5-4151-b80b-bf83c7deef23/200-4 00:34:17.953 --> 00:34:19.172 These embryos were. 9580b482-17f5-4151-b80b-bf83c7deef23/201-0 00:34:19.372 --> 00:34:24.368 where we have left-sided nodal expression. Now if you have this expressed nodal on 9580b482-17f5-4151-b80b-bf83c7deef23/201-1 00:34:24.368 --> 00:34:27.859 the right side, you randomize the process to a very large 9580b482-17f5-4151-b80b-bf83c7deef23/201-2 00:34:27.859 --> 00:34:31.350 number from those, either have right-sided hearts or have 9580b482-17f5-4151-b80b-bf83c7deef23/201-3 00:34:31.350 --> 00:34:34.299 hearts that don't know retreatable. And the gut, 9580b482-17f5-4151-b80b-bf83c7deef23/201-4 00:34:34.299 --> 00:34:38.332 which normally accords in a counterclockwise fashion in all of us, 9580b482-17f5-4151-b80b-bf83c7deef23/202-0 00:34:38.452 --> 00:34:45.824 They're also in the opposite orientation. And of course this is a condition that 9580b482-17f5-4151-b80b-bf83c7deef23/202-1 00:34:45.824 --> 00:34:53.287 happens in in human sinus syndromes and and and indeed it was really very nice to 9580b482-17f5-4151-b80b-bf83c7deef23/202-2 00:34:53.287 --> 00:34:58.292 see from the work of including that of this Robertson. 9580b482-17f5-4151-b80b-bf83c7deef23/203-0 00:34:58.412 --> 00:35:01.892 from Danny Nepson work, Michael King and Hoshi. 9580b482-17f5-4151-b80b-bf83c7deef23/205-0 00:35:04.732 --> 00:35:10.679 And in the chick and many groups simultaneously showed that that left 9580b482-17f5-4151-b80b-bf83c7deef23/205-1 00:35:10.679 --> 00:35:17.136 sided nodal expression is crucial for positioning of the organs and you see 9580b482-17f5-4151-b80b-bf83c7deef23/205-2 00:35:17.136 --> 00:35:23.932 that that this is also present in humans, the human nodal protein when mutated. 9580b482-17f5-4151-b80b-bf83c7deef23/208-0 00:35:23.932 --> 00:35:28.520 is associated with cardiovascular malformations. We also see this, 9580b482-17f5-4151-b80b-bf83c7deef23/208-1 00:35:28.520 --> 00:35:32.354 you know our work was published in the mid to late 90s, 9580b482-17f5-4151-b80b-bf83c7deef23/208-2 00:35:32.354 --> 00:35:35.915 and finding this link to humans took a bit of time, 9580b482-17f5-4151-b80b-bf83c7deef23/208-3 00:35:35.915 --> 00:35:40.982 but it was really very gratifying to see that the basis of cardiovascular 9580b482-17f5-4151-b80b-bf83c7deef23/206-0 00:35:36.292 --> 00:35:36.612 OK. 9580b482-17f5-4151-b80b-bf83c7deef23/207-0 00:35:40.012 --> 00:35:40.132 OK. 9580b482-17f5-4151-b80b-bf83c7deef23/208-4 00:35:40.982 --> 00:35:43.652 malformations, cytus defects in humans. 9580b482-17f5-4151-b80b-bf83c7deef23/209-0 00:35:43.892 --> 00:35:44.332 And. 9580b482-17f5-4151-b80b-bf83c7deef23/210-0 00:35:44.332 --> 00:35:47.973 Is often because of mutations in the protein itself, 9580b482-17f5-4151-b80b-bf83c7deef23/210-1 00:35:47.973 --> 00:35:52.506 and subsequent work from many groups showed that not only itself, 9580b482-17f5-4151-b80b-bf83c7deef23/210-2 00:35:52.506 --> 00:35:57.246 but also its core receptors, the entire signaling cascade downstream 9580b482-17f5-4151-b80b-bf83c7deef23/210-3 00:35:57.246 --> 00:36:01.711 of this growth factor signal. So its receptors and intracellular 9580b482-17f5-4151-b80b-bf83c7deef23/210-4 00:36:01.711 --> 00:36:04.252 effectors, all of these when mutated. 9580b482-17f5-4151-b80b-bf83c7deef23/212-0 00:36:04.332 --> 00:36:11.212 are associated with defects in in not only the the positioning of the heart, 9580b482-17f5-4151-b80b-bf83c7deef23/212-1 00:36:11.212 --> 00:36:17.913 they also have other defects, polysphemia, they have heterotaxy and so on. 9580b482-17f5-4151-b80b-bf83c7deef23/212-2 00:36:17.913 --> 00:36:23.452 So this filamental work that we did in frogs and subsequently 9580b482-17f5-4151-b80b-bf83c7deef23/211-0 00:36:22.492 --> 00:36:24.132 It will be large. 9580b482-17f5-4151-b80b-bf83c7deef23/213-0 00:36:23.612 --> 00:36:28.297 And I went on to work in Singapore. So about this time, 9580b482-17f5-4151-b80b-bf83c7deef23/213-1 00:36:28.297 --> 00:36:33.483 Livan was recruited to a newly formed institute in Singapore. 9580b482-17f5-4151-b80b-bf83c7deef23/213-2 00:36:33.483 --> 00:36:40.175 And so I did a second post-doc in the laboratory of Vladimir Korsch and I I had 9580b482-17f5-4151-b80b-bf83c7deef23/213-3 00:36:40.175 --> 00:36:42.852 in Vanderbilt itself identified. 9580b482-17f5-4151-b80b-bf83c7deef23/215-0 00:36:43.732 --> 00:36:48.035 Nutritionally related genes. So then I I carried this on in in 9580b482-17f5-4151-b80b-bf83c7deef23/215-1 00:36:48.035 --> 00:36:53.431 Singapore in collaboration with Chris Wright and also with Lila Sovieta Kresel 9580b482-17f5-4151-b80b-bf83c7deef23/215-2 00:36:53.431 --> 00:36:57.119 and Marnie Halpern who was at the Carnegie Institute. 9580b482-17f5-4151-b80b-bf83c7deef23/215-3 00:36:57.119 --> 00:37:01.012 Lila had just joined Vanderbilt as a new faculty member. 9580b482-17f5-4151-b80b-bf83c7deef23/214-0 00:37:00.492 --> 00:37:00.732 It's cool. 9580b482-17f5-4151-b80b-bf83c7deef23/216-0 00:37:01.132 --> 00:37:07.268 So what I found was the zebrofish related genes were disrupted in a classical 9580b482-17f5-4151-b80b-bf83c7deef23/216-1 00:37:07.268 --> 00:37:12.066 mutant called cyclops, which had been identified in Eugenian 9580b482-17f5-4151-b80b-bf83c7deef23/216-2 00:37:12.066 --> 00:37:16.471 organ in the 80s in the lab of Chuck Hendel and others. 9580b482-17f5-4151-b80b-bf83c7deef23/216-3 00:37:16.471 --> 00:37:19.932 And this was done by classical mutagenesis. 9580b482-17f5-4151-b80b-bf83c7deef23/217-0 00:37:21.172 --> 00:37:25.780 gamma rays and and subsequently also by by chemical mutagenesis. 9580b482-17f5-4151-b80b-bf83c7deef23/217-1 00:37:25.780 --> 00:37:28.971 And the basis for this mutant was not known, 9580b482-17f5-4151-b80b-bf83c7deef23/217-2 00:37:28.971 --> 00:37:32.161 so as the name indicates in cyclops mutants, 9580b482-17f5-4151-b80b-bf83c7deef23/217-3 00:37:32.161 --> 00:37:37.336 the eyes are fused together similar to the Greek mythological character, 9580b482-17f5-4151-b80b-bf83c7deef23/217-4 00:37:37.336 --> 00:37:38.612 character cyclops. 9580b482-17f5-4151-b80b-bf83c7deef23/218-0 00:37:38.652 --> 00:37:44.655 So what I found was one of the normal genes was actually absent in the deletion 9580b482-17f5-4151-b80b-bf83c7deef23/218-1 00:37:44.655 --> 00:37:50.208 mutant of of fatlux and the expression pattern is altered in these mutant 9580b482-17f5-4151-b80b-bf83c7deef23/218-2 00:37:50.208 --> 00:37:53.960 embryos. And in collaborative work with all these 9580b482-17f5-4151-b80b-bf83c7deef23/218-3 00:37:53.960 --> 00:37:57.262 groups, we then showed that the the venture 9580b482-17f5-4151-b80b-bf83c7deef23/218-4 00:37:57.262 --> 00:37:58.012 forebrain. 9580b482-17f5-4151-b80b-bf83c7deef23/219-0 00:37:58.332 --> 00:38:04.239 And and the therefore the basis of cyclopia is because of defects in the 9580b482-17f5-4151-b80b-bf83c7deef23/219-1 00:38:04.239 --> 00:38:09.904 zebrafish nodal growth factor. So this is of course relevant to human 9580b482-17f5-4151-b80b-bf83c7deef23/219-2 00:38:09.904 --> 00:38:15.083 congenital birth defects. So I I need to give you an alert that 9580b482-17f5-4151-b80b-bf83c7deef23/219-3 00:38:15.083 --> 00:38:15.892 there's a. 9580b482-17f5-4151-b80b-bf83c7deef23/220-0 00:38:16.292 --> 00:38:20.255 horrible picture coming up. So you can see there's this human 9580b482-17f5-4151-b80b-bf83c7deef23/220-1 00:38:20.255 --> 00:38:25.433 condition called holoprosencephaly where you know these these fetuses don't make 9580b482-17f5-4151-b80b-bf83c7deef23/220-2 00:38:25.433 --> 00:38:28.949 it determined. They're often you know lost even before 9580b482-17f5-4151-b80b-bf83c7deef23/220-3 00:38:28.949 --> 00:38:31.825 that. And this is very similar to the human, 9580b482-17f5-4151-b80b-bf83c7deef23/220-4 00:38:31.825 --> 00:38:35.852 this human condition is very similar to the zebu fish cyclops. 9580b482-17f5-4151-b80b-bf83c7deef23/221-0 00:38:35.932 --> 00:38:36.412 Location. 9580b482-17f5-4151-b80b-bf83c7deef23/222-0 00:38:36.412 --> 00:38:41.030 You can see the eyes are close together. In other mutations, 9580b482-17f5-4151-b80b-bf83c7deef23/222-1 00:38:41.030 --> 00:38:47.163 there's a single eye with a single lens. And uh many of these hiliprosencephalin 9580b482-17f5-4151-b80b-bf83c7deef23/222-2 00:38:47.163 --> 00:38:53.068 mutations were later on found to be because of the defects in the human model 9580b482-17f5-4151-b80b-bf83c7deef23/222-3 00:38:53.068 --> 00:38:56.172 and pathway components of the human gene. 9580b482-17f5-4151-b80b-bf83c7deef23/223-0 00:38:56.452 --> 00:39:02.211 So I continue to to be very close and I was really inspired by by these, 9580b482-17f5-4151-b80b-bf83c7deef23/223-1 00:39:02.211 --> 00:39:08.207 these really inspiring women scientists. This is Nelia Somizakresa when she 9580b482-17f5-4151-b80b-bf83c7deef23/223-2 00:39:08.207 --> 00:39:11.914 visited us a few years back and Marnie Halpin, 9580b482-17f5-4151-b80b-bf83c7deef23/223-3 00:39:11.914 --> 00:39:16.332 who I met last year at a fish meeting in in California. 9580b482-17f5-4151-b80b-bf83c7deef23/224-0 00:39:16.412 --> 00:39:20.479 They're both, you know, very prominent in the field and also 9580b482-17f5-4151-b80b-bf83c7deef23/224-1 00:39:20.479 --> 00:39:24.812 chairs of their departments in the medical school at Washington. 9580b482-17f5-4151-b80b-bf83c7deef23/224-2 00:39:24.812 --> 00:39:29.212 Mila just stepped down, and Lani is the chair of the Geser School 9580b482-17f5-4151-b80b-bf83c7deef23/224-3 00:39:29.212 --> 00:39:31.412 of Medicine at Dartmouth Village. 9580b482-17f5-4151-b80b-bf83c7deef23/225-0 00:39:31.452 --> 00:39:36.851 So I've been very fortunate to have worked with really inspiring 9580b482-17f5-4151-b80b-bf83c7deef23/225-1 00:39:36.851 --> 00:39:42.749 collaborators and and inspiring women scientists throughout my career. 9580b482-17f5-4151-b80b-bf83c7deef23/225-2 00:39:42.749 --> 00:39:48.065 So following this work, I I became a fellow at the Institute of 9580b482-17f5-4151-b80b-bf83c7deef23/225-3 00:39:48.065 --> 00:39:50.972 Molecular Agrobiology in Singapore. 9580b482-17f5-4151-b80b-bf83c7deef23/226-0 00:39:51.292 --> 00:39:56.289 And like many others in the field, I tried to work out the reduction 9580b482-17f5-4151-b80b-bf83c7deef23/226-1 00:39:56.289 --> 00:40:01.213 components of the identified model, which is a group factor signal. 9580b482-17f5-4151-b80b-bf83c7deef23/226-2 00:40:01.213 --> 00:40:06.572 We wanted to see what it it how it transduces its signal inside the cell. 9580b482-17f5-4151-b80b-bf83c7deef23/227-0 00:40:06.692 --> 00:40:10.925 And I spent about a year doing this and I was scooped left, 9580b482-17f5-4151-b80b-bf83c7deef23/227-1 00:40:10.925 --> 00:40:14.806 right and centre by very large teams across the world. 9580b482-17f5-4151-b80b-bf83c7deef23/227-2 00:40:14.806 --> 00:40:19.603 This was a very hot area, transforming group factor beta signalling 9580b482-17f5-4151-b80b-bf83c7deef23/227-3 00:40:19.603 --> 00:40:24.612 was being studied by many groups both in the UK and the United States. 9580b482-17f5-4151-b80b-bf83c7deef23/228-0 00:40:24.652 --> 00:40:28.999 And I wasn't making any progress. Any progress I would make would be would 9580b482-17f5-4151-b80b-bf83c7deef23/228-1 00:40:28.999 --> 00:40:33.056 show up in the next issue of of Nature or Cell. And so at this point, 9580b482-17f5-4151-b80b-bf83c7deef23/228-2 00:40:33.056 --> 00:40:37.577 the director of the Institute of Pond Biologist by the name Sundar put me out 9580b482-17f5-4151-b80b-bf83c7deef23/228-3 00:40:37.577 --> 00:40:40.533 and said, why are you doing what everybody else is 9580b482-17f5-4151-b80b-bf83c7deef23/228-4 00:40:40.533 --> 00:40:43.141 doing? This is really you shouldn't be doing 9580b482-17f5-4151-b80b-bf83c7deef23/228-5 00:40:43.141 --> 00:40:44.532 what everybody is doing. 9580b482-17f5-4151-b80b-bf83c7deef23/229-0 00:40:44.652 --> 00:40:50.502 You should really be doing something that's unique and distinctive and gives 9580b482-17f5-4151-b80b-bf83c7deef23/229-1 00:40:50.502 --> 00:40:54.680 you room to grow. And I think this is really very good 9580b482-17f5-4151-b80b-bf83c7deef23/229-2 00:40:54.680 --> 00:40:58.327 advice. And I was able to actually benefit from 9580b482-17f5-4151-b80b-bf83c7deef23/229-3 00:40:58.327 --> 00:41:04.252 this because I also found about that time that one of the little related RNAs 9580b482-17f5-4151-b80b-bf83c7deef23/230-0 00:41:04.252 --> 00:41:08.350 is actually expressed not only in the embryo, 9580b482-17f5-4151-b80b-bf83c7deef23/230-1 00:41:08.350 --> 00:41:15.834 but also present in the ovary in the egg in one little clone at one end of the egg. 9580b482-17f5-4151-b80b-bf83c7deef23/230-2 00:41:15.834 --> 00:41:23.139 And so RNA is being localized in the egg and early embryo in Drosophila and in C. 9580b482-17f5-4151-b80b-bf83c7deef23/230-3 00:41:23.139 --> 00:41:23.852 elegans. 9580b482-17f5-4151-b80b-bf83c7deef23/232-0 00:41:23.852 --> 00:41:29.876 had been found to be very important for positioning various cells and tissues in 9580b482-17f5-4151-b80b-bf83c7deef23/232-1 00:41:29.876 --> 00:41:35.975 neutral embryogenesis. So, fortunately, the institute advisory board comprised of 9580b482-17f5-4151-b80b-bf83c7deef23/232-2 00:41:35.975 --> 00:41:41.478 very eminent scientists, Daniel Lirard, who was the director of the Curie 9580b482-17f5-4151-b80b-bf83c7deef23/232-3 00:41:41.478 --> 00:41:43.412 Institute at the time, and 9580b482-17f5-4151-b80b-bf83c7deef23/233-0 00:41:43.532 --> 00:41:48.112 who was the director general of EMBL Hyderabad. And incidentally, 9580b482-17f5-4151-b80b-bf83c7deef23/233-1 00:41:48.112 --> 00:41:53.455 Fertlis is also the founding president. He established the European Research 9580b482-17f5-4151-b80b-bf83c7deef23/233-2 00:41:53.455 --> 00:41:56.578 Council, which many people throughout Europe 9580b482-17f5-4151-b80b-bf83c7deef23/233-3 00:41:56.578 --> 00:42:01.089 benefit from to this day. So these people could be in touch with 9580b482-17f5-4151-b80b-bf83c7deef23/233-4 00:42:01.089 --> 00:42:01.852 Ana Frithi. 9580b482-17f5-4151-b80b-bf83c7deef23/234-0 00:42:01.972 --> 00:42:05.496 who was at EMBL and arranged for me to visit her lab. 9580b482-17f5-4151-b80b-bf83c7deef23/234-1 00:42:05.496 --> 00:42:09.737 So Anne's lab had been working on localized RNAs in the fly egg. 9580b482-17f5-4151-b80b-bf83c7deef23/234-2 00:42:09.737 --> 00:42:14.761 She had been working on oscar mRNA, which is localized to the posterior core 9580b482-17f5-4151-b80b-bf83c7deef23/234-3 00:42:14.761 --> 00:42:19.067 of the drosophila egg. And it's crucial for finding the germline, 9580b482-17f5-4151-b80b-bf83c7deef23/234-4 00:42:19.067 --> 00:42:21.612 the reproductive structures of the fly. 9580b482-17f5-4151-b80b-bf83c7deef23/235-0 00:42:21.612 --> 00:42:26.442 So I was sent off to Ann's lab, and Ann is really a fantastic person and 9580b482-17f5-4151-b80b-bf83c7deef23/235-1 00:42:26.442 --> 00:42:30.545 a really another inspiring scientist. She's in fact retiring. 9580b482-17f5-4151-b80b-bf83c7deef23/235-2 00:42:30.545 --> 00:42:35.573 Her retiring symposium is tomorrow, which I am unfortunately going to miss. 9580b482-17f5-4151-b80b-bf83c7deef23/235-3 00:42:35.573 --> 00:42:37.492 I had to send her my regrets. 9580b482-17f5-4151-b80b-bf83c7deef23/236-0 00:42:37.692 --> 00:42:44.079 So Alan's lab had been using the fruit fly as a model to understand how RNAs get 9580b482-17f5-4151-b80b-bf83c7deef23/236-1 00:42:44.079 --> 00:42:48.653 localized to one end, how do they generate, in this case, 9580b482-17f5-4151-b80b-bf83c7deef23/236-2 00:42:48.653 --> 00:42:54.172 the germline of the fruit fly. So Eden was working on on a zebrafish. 9580b482-17f5-4151-b80b-bf83c7deef23/237-0 00:42:54.172 --> 00:42:57.276 Army. I was sent there for about for a couple 9580b482-17f5-4151-b80b-bf83c7deef23/237-1 00:42:57.276 --> 00:43:02.270 of months and it was really a very nice atmosphere because I could learn, 9580b482-17f5-4151-b80b-bf83c7deef23/237-2 00:43:02.270 --> 00:43:07.061 I could see what techniques they were using and then adapt them and to 9580b482-17f5-4151-b80b-bf83c7deef23/237-3 00:43:07.061 --> 00:43:10.436 zebrafish. And so I came back and then started my 9580b482-17f5-4151-b80b-bf83c7deef23/237-4 00:43:10.436 --> 00:43:14.012 own program looking at localization of these armies. 9580b482-17f5-4151-b80b-bf83c7deef23/238-0 00:43:14.172 --> 00:43:20.736 In zebrafish eggs and about this time also our son was born shown here and the 9580b482-17f5-4151-b80b-bf83c7deef23/238-1 00:43:20.736 --> 00:43:24.558 institute did not have a child care facility. 9580b482-17f5-4151-b80b-bf83c7deef23/238-2 00:43:24.558 --> 00:43:28.547 So I was very fortunate to lean on our parents. 9580b482-17f5-4151-b80b-bf83c7deef23/238-3 00:43:28.547 --> 00:43:33.532 So this is Mohan's parents and here are my parents, my dad. 9580b482-17f5-4151-b80b-bf83c7deef23/239-0 00:43:34.052 --> 00:43:37.948 here today for childcare. And because the institute didn't have a 9580b482-17f5-4151-b80b-bf83c7deef23/239-1 00:43:37.948 --> 00:43:40.841 daycare facility, I then tried to to set up one, 9580b482-17f5-4151-b80b-bf83c7deef23/239-2 00:43:40.841 --> 00:43:44.501 but it just took, you know, finding the money, the approvals, 9580b482-17f5-4151-b80b-bf83c7deef23/239-3 00:43:44.501 --> 00:43:48.219 everything took so long. My son was five years old by the time 9580b482-17f5-4151-b80b-bf83c7deef23/239-4 00:43:48.219 --> 00:43:52.174 that that I was actually able to do this. Yeah, even in Singapore, 9580b482-17f5-4151-b80b-bf83c7deef23/239-5 00:43:52.174 --> 00:43:53.532 these things take time. 9580b482-17f5-4151-b80b-bf83c7deef23/240-0 00:43:53.852 --> 00:43:58.493 But I think I I'd like to think that, you know, whatever I do in science, 9580b482-17f5-4151-b80b-bf83c7deef23/240-1 00:43:58.493 --> 00:44:03.322 you know, this is perhaps, you know, more important because it enabled a lot 9580b482-17f5-4151-b80b-bf83c7deef23/240-2 00:44:03.322 --> 00:44:08.402 of young people to actually be able to continue working in in those early stages 9580b482-17f5-4151-b80b-bf83c7deef23/240-3 00:44:08.402 --> 00:44:11.412 of their career when they need so much support. 9580b482-17f5-4151-b80b-bf83c7deef23/241-0 00:44:11.612 --> 00:44:16.536 OK. And so then in my new lab, I started to look at little limb RNAs and 9580b482-17f5-4151-b80b-bf83c7deef23/241-1 00:44:16.536 --> 00:44:20.246 how they are distributed in in early eggs and embryos. 9580b482-17f5-4151-b80b-bf83c7deef23/241-2 00:44:20.246 --> 00:44:25.439 So here's a nodal RNA that we found distributed in two daughter cells at the 9580b482-17f5-4151-b80b-bf83c7deef23/241-3 00:44:25.439 --> 00:44:29.014 four cell stage. And I have to say I had some really 9580b482-17f5-4151-b80b-bf83c7deef23/241-4 00:44:29.014 --> 00:44:31.172 fantastic students and postdocs. 9580b482-17f5-4151-b80b-bf83c7deef23/242-0 00:44:31.452 --> 00:44:35.355 who then really drove this direction. And Anike, 9580b482-17f5-4151-b80b-bf83c7deef23/242-1 00:44:35.355 --> 00:44:39.975 who's who was the first student to actually join the lab, 9580b482-17f5-4151-b80b-bf83c7deef23/242-2 00:44:39.975 --> 00:44:43.719 the first PhD student, he's currently working, 9580b482-17f5-4151-b80b-bf83c7deef23/242-3 00:44:43.719 --> 00:44:49.852 he's leading the entire East Coast of the United States for Oxford Manipore. 9580b482-17f5-4151-b80b-bf83c7deef23/244-0 00:44:49.932 --> 00:44:53.229 So he's really gone on to be very successful. 9580b482-17f5-4151-b80b-bf83c7deef23/244-1 00:44:53.229 --> 00:44:57.745 So he generated synthetic little mRNA. We saw some tags on it. 9580b482-17f5-4151-b80b-bf83c7deef23/244-2 00:44:57.745 --> 00:45:03.121 And because zebrafish eggs are very amenable to experimental manipulation, 9580b482-17f5-4151-b80b-bf83c7deef23/244-3 00:45:03.121 --> 00:45:07.422 he injected it and using the transparency of the zebrafish, 9580b482-17f5-4151-b80b-bf83c7deef23/243-0 00:45:05.012 --> 00:45:05.212 No. 9580b482-17f5-4151-b80b-bf83c7deef23/244-4 00:45:07.422 --> 00:45:09.572 we could then do live imaging. 9580b482-17f5-4151-b80b-bf83c7deef23/246-0 00:45:09.852 --> 00:45:15.118 and see that the synthetic RNA also went to two daughter cells at the four cell 9580b482-17f5-4151-b80b-bf83c7deef23/245-0 00:45:14.132 --> 00:45:15.332 Yeah. 9580b482-17f5-4151-b80b-bf83c7deef23/246-1 00:45:15.118 --> 00:45:17.882 stage. So what are these these cells that 9580b482-17f5-4151-b80b-bf83c7deef23/246-2 00:45:17.882 --> 00:45:22.819 inherit this RNA? So to test that, what we did was to actually inject that 9580b482-17f5-4151-b80b-bf83c7deef23/246-3 00:45:22.819 --> 00:45:27.952 fluorescence reporter and then actually dissect out normally using an eyelash 9580b482-17f5-4151-b80b-bf83c7deef23/246-4 00:45:27.952 --> 00:45:29.532 tool, removing the cells 9580b482-17f5-4151-b80b-bf83c7deef23/247-0 00:45:29.532 --> 00:45:33.801 Contain the fluorescent RNA. And normally this is what a little fish 9580b482-17f5-4151-b80b-bf83c7deef23/247-1 00:45:33.801 --> 00:45:38.317 egg looks 24 hours after conception. There's the eye, there's the brain. 9580b482-17f5-4151-b80b-bf83c7deef23/247-2 00:45:38.317 --> 00:45:42.338 The heart would be beating here and there's the spinal cord. OK, 9580b482-17f5-4151-b80b-bf83c7deef23/247-3 00:45:42.338 --> 00:45:46.359 but then in these embolos where we have removed those two cells, 9580b482-17f5-4151-b80b-bf83c7deef23/247-4 00:45:46.359 --> 00:45:49.452 we actually don't have a head. OK, these embolos. 9580b482-17f5-4151-b80b-bf83c7deef23/248-0 00:45:49.532 --> 00:45:55.194 Black anterior and dorsal structures. So the cells that contain the RNA are 9580b482-17f5-4151-b80b-bf83c7deef23/248-1 00:45:55.194 --> 00:46:00.261 crucial for the feet of these anterior dorsal structures, the head. 9580b482-17f5-4151-b80b-bf83c7deef23/248-2 00:46:00.261 --> 00:46:05.997 And this is shown with marker genes. So here is Sonic hedgehog expression in 9580b482-17f5-4151-b80b-bf83c7deef23/248-3 00:46:05.997 --> 00:46:09.052 the fore, mid, hindbrain and spinal cord. 9580b482-17f5-4151-b80b-bf83c7deef23/249-0 00:46:09.132 --> 00:46:16.049 you can see in these quintremoved cells, there's hardly any or no expression of 9580b482-17f5-4151-b80b-bf83c7deef23/249-1 00:46:16.049 --> 00:46:20.718 Sonic hedgehog. So these RNAs have to be inherited by 9580b482-17f5-4151-b80b-bf83c7deef23/249-2 00:46:20.718 --> 00:46:26.425 these cells to form these important head and anterior structures. 9580b482-17f5-4151-b80b-bf83c7deef23/249-3 00:46:26.425 --> 00:46:28.932 So this was work we published 9580b482-17f5-4151-b80b-bf83c7deef23/250-0 00:46:29.052 --> 00:46:34.409 in nature and and Anika and Patrick were really crucial for this work and also 9580b482-17f5-4151-b80b-bf83c7deef23/250-1 00:46:34.409 --> 00:46:37.528 Albert Chung who was a technician in the lab. 9580b482-17f5-4151-b80b-bf83c7deef23/250-2 00:46:37.528 --> 00:46:43.156 This was again done collaboratively with Shingo Maigawa in Eric Rivenberg's lab at 9580b482-17f5-4151-b80b-bf83c7deef23/250-3 00:46:43.156 --> 00:46:46.411 Penn. So I was very fortunate to have very good 9580b482-17f5-4151-b80b-bf83c7deef23/250-4 00:46:46.411 --> 00:46:48.852 collaborators who actually helped us 9580b482-17f5-4151-b80b-bf83c7deef23/251-0 00:46:48.972 --> 00:46:53.195 out this work. Patrick came from a lab that had been 9580b482-17f5-4151-b80b-bf83c7deef23/251-1 00:46:53.195 --> 00:46:59.171 looking at you know evolutionary conservation of of regulatory elements in 9580b482-17f5-4151-b80b-bf83c7deef23/251-2 00:46:59.171 --> 00:47:05.784 the mouse and and food and other species. So he basically went to a fish market in 9580b482-17f5-4151-b80b-bf83c7deef23/251-3 00:47:05.784 --> 00:47:08.572 Singapore and the next thing I knew 9580b482-17f5-4151-b80b-bf83c7deef23/253-0 00:47:08.572 --> 00:47:12.739 The lab was full of like little pots of like all kinds of fish swimming about and 9580b482-17f5-4151-b80b-bf83c7deef23/253-1 00:47:12.739 --> 00:47:15.839 this is really something that he could do very easily there. 9580b482-17f5-4151-b80b-bf83c7deef23/253-2 00:47:15.839 --> 00:47:19.447 He could just walk through a market, buy a bunch of different species, 9580b482-17f5-4151-b80b-bf83c7deef23/253-3 00:47:19.447 --> 00:47:23.461 bring them back to the lab and he smashed them up and he what he did was to to 9580b482-17f5-4151-b80b-bf83c7deef23/253-4 00:47:23.461 --> 00:47:27.425 isolate DNA and RNA from these and then looked at the little sequences in all 9580b482-17f5-4151-b80b-bf83c7deef23/253-5 00:47:27.425 --> 00:47:28.492 these different fish. 9580b482-17f5-4151-b80b-bf83c7deef23/254-0 00:47:28.692 --> 00:47:34.941 And by by aligning them with zebrafish, he was able to identify signatures that 9580b482-17f5-4151-b80b-bf83c7deef23/254-1 00:47:34.941 --> 00:47:39.080 seem to be present in in all these fish species. OK, 9580b482-17f5-4151-b80b-bf83c7deef23/254-2 00:47:39.080 --> 00:47:43.532 so he then also compared this. Sorry, I went a bit fast. 9580b482-17f5-4151-b80b-bf83c7deef23/255-0 00:47:43.612 --> 00:47:50.116 He also found that some of these were found also in human dogs and chill 9580b482-17f5-4151-b80b-bf83c7deef23/255-1 00:47:50.116 --> 00:47:55.283 sequences that other people had had previously published. 9580b482-17f5-4151-b80b-bf83c7deef23/255-2 00:47:55.283 --> 00:47:59.292 So he was able to find these signatures and. 9580b482-17f5-4151-b80b-bf83c7deef23/256-0 00:47:59.492 --> 00:48:03.748 Usually this region which have these signatures sequences. 9580b482-17f5-4151-b80b-bf83c7deef23/256-1 00:48:03.748 --> 00:48:09.013 So these are sort of like pin codes in your mail at mailing address. OK, 9580b482-17f5-4151-b80b-bf83c7deef23/256-2 00:48:09.013 --> 00:48:13.340 so if we say CB47AL, we know our mails shouldn't come here, 9580b482-17f5-4151-b80b-bf83c7deef23/256-3 00:48:13.340 --> 00:48:17.812 but then if you scramble this code and you need to see B7AL4. 9580b482-17f5-4151-b80b-bf83c7deef23/257-0 00:48:18.732 --> 00:48:21.923 I don't know where in Coventry it's going to end up. OK, 9580b482-17f5-4151-b80b-bf83c7deef23/257-1 00:48:21.923 --> 00:48:26.009 or you could delete out regions in between. You could be on the C&L, 9580b482-17f5-4151-b80b-bf83c7deef23/257-2 00:48:26.009 --> 00:48:28.808 you know, the post office doesn't know what to do 9580b482-17f5-4151-b80b-bf83c7deef23/257-3 00:48:28.808 --> 00:48:31.999 with your meal. And essentially that's what happens with 9580b482-17f5-4151-b80b-bf83c7deef23/257-4 00:48:31.999 --> 00:48:35.413 these sequences as well. These are recognized by the similar 9580b482-17f5-4151-b80b-bf83c7deef23/257-5 00:48:35.413 --> 00:48:38.156 machinery, sorted and then putting them into the 9580b482-17f5-4151-b80b-bf83c7deef23/257-6 00:48:38.156 --> 00:48:38.492 right. 9580b482-17f5-4151-b80b-bf83c7deef23/258-0 00:48:38.572 --> 00:48:43.400 cells at the right time. And Patrick essentially identified the 9580b482-17f5-4151-b80b-bf83c7deef23/258-1 00:48:43.400 --> 00:48:48.907 key protein that recognizes these elements by purifying the complex that 9580b482-17f5-4151-b80b-bf83c7deef23/258-2 00:48:48.907 --> 00:48:54.791 binds to this RNA. And through this, we were able to identify the key protein 9580b482-17f5-4151-b80b-bf83c7deef23/258-3 00:48:54.791 --> 00:48:58.412 VIBOX1, which we work on in my lab to this day. 9580b482-17f5-4151-b80b-bf83c7deef23/259-0 00:48:58.612 --> 00:49:04.075 in BiBox 1 actually result in the RNA instead of going to two daughter cells, 9580b482-17f5-4151-b80b-bf83c7deef23/259-1 00:49:04.075 --> 00:49:09.678 ends up as a blob in in the egg itself. It doesn't get distributed to the right 9580b482-17f5-4151-b80b-bf83c7deef23/259-2 00:49:09.678 --> 00:49:13.740 cells, right time. We also made other mutations to remove 9580b482-17f5-4151-b80b-bf83c7deef23/259-3 00:49:13.740 --> 00:49:18.292 the the pin code itself. And we also found the sorting machinery 9580b482-17f5-4151-b80b-bf83c7deef23/260-0 00:49:18.452 --> 00:49:22.149 the main key components, the microtubule cytoskeleton, 9580b482-17f5-4151-b80b-bf83c7deef23/260-1 00:49:22.149 --> 00:49:25.375 which transmits the RNA to the hood order cell. 9580b482-17f5-4151-b80b-bf83c7deef23/260-2 00:49:25.375 --> 00:49:28.534 So I'm I'm actually summarizing probably many, 9580b482-17f5-4151-b80b-bf83c7deef23/260-3 00:49:28.534 --> 00:49:33.575 many years of work by many talented students in the lab. So here's Shinin, 9580b482-17f5-4151-b80b-bf83c7deef23/260-4 00:49:33.575 --> 00:49:38.212 who made the mutations in the little three prime UTR, and that's the 9580b482-17f5-4151-b80b-bf83c7deef23/261-0 00:49:38.252 --> 00:49:43.493 Cake she got when her paper was published, showing the two daughter cells there. 9580b482-17f5-4151-b80b-bf83c7deef23/261-1 00:49:43.493 --> 00:49:46.535 Yeah, my lab's always been partial to desserts 9580b482-17f5-4151-b80b-bf83c7deef23/261-2 00:49:46.535 --> 00:49:50.805 and cake in particular. So this is a very long standing tradition 9580b482-17f5-4151-b80b-bf83c7deef23/261-3 00:49:50.805 --> 00:49:54.946 and Pooja did the work on Y box 1. So following Patrick's work, 9580b482-17f5-4151-b80b-bf83c7deef23/261-4 00:49:54.946 --> 00:49:58.052 she she studied the the genome editing mutants. 9580b482-17f5-4151-b80b-bf83c7deef23/262-0 00:49:58.212 --> 00:50:04.402 umm in AMI box 1 and showed that the RNA is mislocalized and then Tran identified 9580b482-17f5-4151-b80b-bf83c7deef23/262-1 00:50:04.402 --> 00:50:10.592 the the microtubule tracks through which the RNA is actually transported and sent 9580b482-17f5-4151-b80b-bf83c7deef23/262-2 00:50:10.592 --> 00:50:15.348 to the correct location. So essentially the the the the poster 9580b482-17f5-4151-b80b-bf83c7deef23/262-3 00:50:15.348 --> 00:50:17.612 machinery is that if you will. 9580b482-17f5-4151-b80b-bf83c7deef23/263-0 00:50:17.692 --> 00:50:22.200 And here they are as graduates. And this is Shijie, 9580b482-17f5-4151-b80b-bf83c7deef23/263-1 00:50:22.200 --> 00:50:28.529 who is actually working on a different JiJie beta signal, the signaling, 9580b482-17f5-4151-b80b-bf83c7deef23/263-2 00:50:28.529 --> 00:50:32.344 and how it's regulated in the early embryo. 9580b482-17f5-4151-b80b-bf83c7deef23/263-3 00:50:32.344 --> 00:50:37.372 So we had identified a crucial pin code, which allows the 9580b482-17f5-4151-b80b-bf83c7deef23/264-0 00:50:37.412 --> 00:50:40.780 Signal RNA to be turned on to the right place, right time. 9580b482-17f5-4151-b80b-bf83c7deef23/264-1 00:50:40.780 --> 00:50:45.175 It also sends it to the correct location. So it's these RNAs are made in the 9580b482-17f5-4151-b80b-bf83c7deef23/264-2 00:50:45.175 --> 00:50:48.029 nucleus, but they need to be distributed in these 9580b482-17f5-4151-b80b-bf83c7deef23/264-3 00:50:48.029 --> 00:50:52.652 two daughter cells because if you remove these cells, you don't have a head, OK. 9580b482-17f5-4151-b80b-bf83c7deef23/265-0 00:50:53.092 --> 00:50:56.866 And we also need to keep it in a certain seat. You need to, 9580b482-17f5-4151-b80b-bf83c7deef23/265-1 00:50:56.866 --> 00:51:01.834 you can't have it turn on too soon. You need to turn it on at the right place, 9580b482-17f5-4151-b80b-bf83c7deef23/265-2 00:51:01.834 --> 00:51:05.042 right time. And that's what that that complex that 9580b482-17f5-4151-b80b-bf83c7deef23/265-3 00:51:05.042 --> 00:51:08.941 Patrick had purified does. You turn it on at the right place, 9580b482-17f5-4151-b80b-bf83c7deef23/265-4 00:51:08.941 --> 00:51:12.652 right time and then allow the signal to to be distributed. 9580b482-17f5-4151-b80b-bf83c7deef23/266-0 00:51:12.932 --> 00:51:17.141 So if you turn it on too soon, you actually also create problems with 9580b482-17f5-4151-b80b-bf83c7deef23/266-1 00:51:17.141 --> 00:51:20.327 the embryo. They start to differentiate in ways that 9580b482-17f5-4151-b80b-bf83c7deef23/266-2 00:51:20.327 --> 00:51:24.055 they would normally not do, and I'll come back to this later. 9580b482-17f5-4151-b80b-bf83c7deef23/266-3 00:51:24.055 --> 00:51:27.241 If you don't have any signal, that's also a problem. 9580b482-17f5-4151-b80b-bf83c7deef23/266-4 00:51:27.241 --> 00:51:30.728 You get cycloplas and you miss chunks of the spinal cord, 9580b482-17f5-4151-b80b-bf83c7deef23/266-5 00:51:30.728 --> 00:51:32.772 and that also leads to illegality. 9580b482-17f5-4151-b80b-bf83c7deef23/268-0 00:51:32.772 --> 00:51:36.371 So I think you need to have these turn on at the right place, 9580b482-17f5-4151-b80b-bf83c7deef23/268-1 00:51:36.371 --> 00:51:39.564 right time and the right level. So what controls this? 9580b482-17f5-4151-b80b-bf83c7deef23/268-2 00:51:39.564 --> 00:51:43.918 So this is something that we will then spend some time trying to work out. 9580b482-17f5-4151-b80b-bf83c7deef23/268-3 00:51:43.918 --> 00:51:48.621 So these are all group factor signals. They're made by one cell and then somehow 9580b482-17f5-4151-b80b-bf83c7deef23/268-4 00:51:48.621 --> 00:51:52.452 sent out and then another cell should then receive this and then. 9580b482-17f5-4151-b80b-bf83c7deef23/269-0 00:51:52.532 --> 00:51:57.423 the song. So how how does this happen? And of course, we got from the, 9580b482-17f5-4151-b80b-bf83c7deef23/269-1 00:51:57.423 --> 00:52:02.245 we know from the really similar work that that the the concentration, 9580b482-17f5-4151-b80b-bf83c7deef23/269-2 00:52:02.245 --> 00:52:07.274 the amount of of a morphogen, of a growth factor signal is very crucial. 9580b482-17f5-4151-b80b-bf83c7deef23/269-3 00:52:07.274 --> 00:52:12.372 For cells that are very close to the source, we receive very high amounts 9580b482-17f5-4151-b80b-bf83c7deef23/271-0 00:52:12.452 --> 00:52:16.039 And as we go further and further away from the source, 9580b482-17f5-4151-b80b-bf83c7deef23/271-1 00:52:16.039 --> 00:52:20.604 we'll see less and less of it. And that actually has an impact on how 9580b482-17f5-4151-b80b-bf83c7deef23/271-2 00:52:20.604 --> 00:52:25.299 the cells respond and how what they turn into. So how does this happen? 9580b482-17f5-4151-b80b-bf83c7deef23/271-3 00:52:25.299 --> 00:52:30.386 So we know that the levels are important because if you have neuronal signal, 9580b482-17f5-4151-b80b-bf83c7deef23/271-4 00:52:30.386 --> 00:52:32.212 you basically get cyclopent. 9580b482-17f5-4151-b80b-bf83c7deef23/272-0 00:52:32.732 --> 00:52:32.852 Here. 9580b482-17f5-4151-b80b-bf83c7deef23/273-0 00:52:32.852 --> 00:52:36.227 We have a little bit. You get eyes that are close together, 9580b482-17f5-4151-b80b-bf83c7deef23/273-1 00:52:36.227 --> 00:52:39.715 but not completely fused. But they're also not normal because 9580b482-17f5-4151-b80b-bf83c7deef23/273-2 00:52:39.715 --> 00:52:43.540 they're lacking parts of the ventral brain, and so on and so forth. 9580b482-17f5-4151-b80b-bf83c7deef23/273-3 00:52:43.540 --> 00:52:46.015 And similarly, if we put too much of nodal, 9580b482-17f5-4151-b80b-bf83c7deef23/273-4 00:52:46.015 --> 00:52:49.783 that also leads to problems. So you're basically instead of having 9580b482-17f5-4151-b80b-bf83c7deef23/273-5 00:52:49.783 --> 00:52:52.652 this nice French flag, you actually have too much. 9580b482-17f5-4151-b80b-bf83c7deef23/274-0 00:52:52.852 --> 00:52:58.318 or too little of of one or other color, which is devastating for the embryo 9580b482-17f5-4151-b80b-bf83c7deef23/274-1 00:52:58.318 --> 00:53:01.697 itself. So when does the signal get turned on? 9580b482-17f5-4151-b80b-bf83c7deef23/274-2 00:53:01.697 --> 00:53:05.581 This was figured out by Pinjin, a student in the lab. 9580b482-17f5-4151-b80b-bf83c7deef23/274-3 00:53:05.581 --> 00:53:11.046 And I was really very pleased to see her then go on to to establish her own 9580b482-17f5-4151-b80b-bf83c7deef23/274-4 00:53:11.046 --> 00:53:12.772 research group in China. 9580b482-17f5-4151-b80b-bf83c7deef23/275-0 00:53:12.932 --> 00:53:18.478 And there she is with her students, where she's continuing to work on on 9580b482-17f5-4151-b80b-bf83c7deef23/275-1 00:53:18.478 --> 00:53:22.580 fundamentally fundamental problems in in development, 9580b482-17f5-4151-b80b-bf83c7deef23/275-2 00:53:22.580 --> 00:53:26.531 not only in in the zebrafish but also in the mouse. 9580b482-17f5-4151-b80b-bf83c7deef23/275-3 00:53:26.531 --> 00:53:32.532 And here's another trainee from my lab. This is Ruan Hua and this is actually. 9580b482-17f5-4151-b80b-bf83c7deef23/276-0 00:53:32.612 --> 00:53:37.224 Wan Zhang was in Lun's lab, so they've all gone back to lead their 9580b482-17f5-4151-b80b-bf83c7deef23/276-1 00:53:37.224 --> 00:53:42.042 own teams in China as group leaders. So Wan was part of a large scale 9580b482-17f5-4151-b80b-bf83c7deef23/276-2 00:53:42.042 --> 00:53:46.310 midgenesis school. So in addition to studying these pathways, 9580b482-17f5-4151-b80b-bf83c7deef23/276-3 00:53:46.310 --> 00:53:51.197 we also developed a lot of tools along the way which were not present, 9580b482-17f5-4151-b80b-bf83c7deef23/276-4 00:53:51.197 --> 00:53:52.092 so using the. 9580b482-17f5-4151-b80b-bf83c7deef23/277-0 00:53:52.332 --> 00:53:58.127 ACDS plant transfers on system. We generated a bank of meetings and was 9580b482-17f5-4151-b80b-bf83c7deef23/277-1 00:53:58.127 --> 00:54:04.728 part of the team that that worked on this very large effort by many, many groups. 9580b482-17f5-4151-b80b-bf83c7deef23/277-2 00:54:04.728 --> 00:54:10.684 And I again had a chance to collaborate with her in in looking at another 9580b482-17f5-4151-b80b-bf83c7deef23/277-3 00:54:10.684 --> 00:54:12.052 civilian pathway. 9580b482-17f5-4151-b80b-bf83c7deef23/278-0 00:54:12.212 --> 00:54:18.814 Has signaling and it's real in in fertilization in the egg some years later. 9580b482-17f5-4151-b80b-bf83c7deef23/278-1 00:54:18.814 --> 00:54:25.759 So we we also looked at how the the nodal growth factor itself is is distributed 9580b482-17f5-4151-b80b-bf83c7deef23/278-2 00:54:25.759 --> 00:54:31.332 and this was work done by by a student on in collaboration with. 9580b482-17f5-4151-b80b-bf83c7deef23/279-0 00:54:31.732 --> 00:54:36.374 um who's a biophysicist, and and he helped us to determine not 9580b482-17f5-4151-b80b-bf83c7deef23/279-1 00:54:36.374 --> 00:54:41.827 only the the diffusivity of this growth factor in vivo in living embryos, 9580b482-17f5-4151-b80b-bf83c7deef23/279-2 00:54:41.827 --> 00:54:47.574 we also looked at the binding affinity to its receptors in the living embryo, 9580b482-17f5-4151-b80b-bf83c7deef23/279-3 00:54:47.574 --> 00:54:51.332 and we were able to to model this computationally. 9580b482-17f5-4151-b80b-bf83c7deef23/280-0 00:54:51.332 --> 00:54:55.155 as well. So this was work that we did together 9580b482-17f5-4151-b80b-bf83c7deef23/280-1 00:54:55.155 --> 00:54:59.628 with Thorsten and we continue to collaborate with him. 9580b482-17f5-4151-b80b-bf83c7deef23/280-2 00:54:59.628 --> 00:55:05.483 We have a paper that we hope will come out very soon in communications, 9580b482-17f5-4151-b80b-bf83c7deef23/280-3 00:55:05.483 --> 00:55:10.932 following up on this work we did on the gradient. So this work was 9580b482-17f5-4151-b80b-bf83c7deef23/281-0 00:55:11.012 --> 00:55:16.254 It's also complemented by by other technological advances that we were 9580b482-17f5-4151-b80b-bf83c7deef23/281-1 00:55:16.254 --> 00:55:20.906 contributing towards. So we generated genome editing deletions 9580b482-17f5-4151-b80b-bf83c7deef23/281-2 00:55:20.906 --> 00:55:26.517 in targeted regions of the genome, and this was published in Genome Biology 9580b482-17f5-4151-b80b-bf83c7deef23/281-3 00:55:26.517 --> 00:55:28.732 and you can see one in a shim. 9580b482-17f5-4151-b80b-bf83c7deef23/282-0 00:55:29.092 --> 00:55:33.790 Celebrating this with this publication with their cake. 9580b482-17f5-4151-b80b-bf83c7deef23/282-1 00:55:33.790 --> 00:55:38.403 So around this time the lab was getting ready to room. 9580b482-17f5-4151-b80b-bf83c7deef23/282-2 00:55:38.403 --> 00:55:45.114 So we had a lab retreat in in Bintan in and this was a picture taken by the lab 9580b482-17f5-4151-b80b-bf83c7deef23/282-3 00:55:45.114 --> 00:55:48.972 at that time and some of you might recognize. 9580b482-17f5-4151-b80b-bf83c7deef23/283-0 00:55:49.212 --> 00:55:49.572 Mr. 9580b482-17f5-4151-b80b-bf83c7deef23/284-0 00:55:49.572 --> 00:55:55.413 I had a woman here, Pavly Vrlichak, who then came to to 糖心TV to 1st set up 9580b482-17f5-4151-b80b-bf83c7deef23/284-1 00:55:55.413 --> 00:55:59.158 the lab. So I was very fortunate that some of the 9580b482-17f5-4151-b80b-bf83c7deef23/284-2 00:55:59.158 --> 00:56:04.924 team that was in Singapore could come here and help me set up the new lab in 9580b482-17f5-4151-b80b-bf83c7deef23/284-3 00:56:04.924 --> 00:56:09.193 this new place. So Pavly was part of the the large scale 9580b482-17f5-4151-b80b-bf83c7deef23/284-4 00:56:09.193 --> 00:56:09.492 lab. 9580b482-17f5-4151-b80b-bf83c7deef23/285-0 00:56:09.572 --> 00:56:13.749 gene screen that we did in the ACDS transposon. So, 9580b482-17f5-4151-b80b-bf83c7deef23/285-1 00:56:13.749 --> 00:56:17.605 Helen was the lead for the functional analysis. 9580b482-17f5-4151-b80b-bf83c7deef23/285-2 00:56:17.605 --> 00:56:22.023 Harvey essentially mapped where these sensations were. 9580b482-17f5-4151-b80b-bf83c7deef23/285-3 00:56:22.023 --> 00:56:26.200 And we did this in collaboration with Sean Burgess, 9580b482-17f5-4151-b80b-bf83c7deef23/285-4 00:56:26.200 --> 00:56:29.172 who's the head of functional genomics 9580b482-17f5-4151-b80b-bf83c7deef23/286-0 00:56:29.252 --> 00:56:35.212 At NIH, not a very easy job these days, but he helped us with this work. 9580b482-17f5-4151-b80b-bf83c7deef23/286-1 00:56:35.212 --> 00:56:39.131 So Parde was the first person who moved across. 9580b482-17f5-4151-b80b-bf83c7deef23/286-2 00:56:39.131 --> 00:56:45.745 So while we were wiping the lab down in Singapore and things were being shipped, 9580b482-17f5-4151-b80b-bf83c7deef23/286-3 00:56:45.745 --> 00:56:49.092 he just sat and did this computation lab. 9580b482-17f5-4151-b80b-bf83c7deef23/287-0 00:56:49.172 --> 00:56:53.869 Analysis was really very, very helpful and this was published in G3 9580b482-17f5-4151-b80b-bf83c7deef23/287-1 00:56:53.869 --> 00:56:59.327 as back-to-back papers and we took this whole collection of hundreds of mutant 9580b482-17f5-4151-b80b-bf83c7deef23/287-2 00:56:59.327 --> 00:57:04.438 lines and deposited them with the European Zebra Fish Resource Center and 9580b482-17f5-4151-b80b-bf83c7deef23/287-3 00:57:04.438 --> 00:57:08.652 I'm very grateful to the White Impact Fund which allowed us. 9580b482-17f5-4151-b80b-bf83c7deef23/288-0 00:57:08.772 --> 00:57:14.947 To to actually deposit this collection as a resource that can be used freely by the 9580b482-17f5-4151-b80b-bf83c7deef23/288-1 00:57:14.947 --> 00:57:19.210 worldwide community. So Sadesh Kumar really helped us get 9580b482-17f5-4151-b80b-bf83c7deef23/288-2 00:57:19.210 --> 00:57:23.106 these funds. So we have to build a new fish facility 9580b482-17f5-4151-b80b-bf83c7deef23/288-3 00:57:23.106 --> 00:57:28.692 here and this was enabled by a Wellcome Trust International Award to Mohan. 9580b482-17f5-4151-b80b-bf83c7deef23/289-0 00:57:28.692 --> 00:57:33.498 Which also allowed us to to to to match with funds from 糖心TV to build this 9580b482-17f5-4151-b80b-bf83c7deef23/289-1 00:57:33.498 --> 00:57:37.257 museum for facility. This is the early days of the facility. 9580b482-17f5-4151-b80b-bf83c7deef23/289-2 00:57:37.257 --> 00:57:40.645 You might recognize some of the people from that time. 9580b482-17f5-4151-b80b-bf83c7deef23/289-3 00:57:40.645 --> 00:57:44.897 Ian and Sarah are still there. So this was and we celebrated this of 9580b482-17f5-4151-b80b-bf83c7deef23/289-4 00:57:44.897 --> 00:57:48.532 course with the symposium and this key was actually built. 9580b482-17f5-4151-b80b-bf83c7deef23/290-0 00:57:48.652 --> 00:57:53.118 by by Lavinia Sivasanmukkal. You can see the lovely fish here. 9580b482-17f5-4151-b80b-bf83c7deef23/290-1 00:57:53.118 --> 00:57:57.796 They were all species, but it was still delicious. So at 糖心TV, 9580b482-17f5-4151-b80b-bf83c7deef23/290-2 00:57:57.796 --> 00:58:01.411 what did we do? So building on our findings in the 9580b482-17f5-4151-b80b-bf83c7deef23/290-3 00:58:01.411 --> 00:58:05.522 zebrafish models, by we I mean Jan Gorotkin at the Center 9580b482-17f5-4151-b80b-bf83c7deef23/290-4 00:58:05.522 --> 00:58:07.932 for Non-coding RNAs in Copenhagen. 9580b482-17f5-4151-b80b-bf83c7deef23/291-0 00:58:08.372 --> 00:58:14.665 Looked at all the mammalian sequences and tried to see where these pin codes that 9580b482-17f5-4151-b80b-bf83c7deef23/291-1 00:58:14.665 --> 00:58:20.344 we'd identified in zebrafish fell. And then this was work done by Andreas 9580b482-17f5-4151-b80b-bf83c7deef23/291-2 00:58:20.344 --> 00:58:24.719 Salker and Agnieszka in collaboration with Jan Brosnans. 9580b482-17f5-4151-b80b-bf83c7deef23/291-3 00:58:24.719 --> 00:58:28.172 What we did was to then look at the complex. 9580b482-17f5-4151-b80b-bf83c7deef23/292-0 00:58:28.292 --> 00:58:28.412 Look. 9580b482-17f5-4151-b80b-bf83c7deef23/293-0 00:58:28.772 --> 00:58:33.783 Take human nodal pin code sequences, put them into zebrafish and lo and behold, 9580b482-17f5-4151-b80b-bf83c7deef23/293-1 00:58:33.783 --> 00:58:38.607 those pin codes from here still make it to the correct address in zebrafish. 9580b482-17f5-4151-b80b-bf83c7deef23/293-2 00:58:38.607 --> 00:58:43.054 So this machinery is concerned and recognized by the cellular factors. 9580b482-17f5-4151-b80b-bf83c7deef23/293-3 00:58:43.054 --> 00:58:48.128 We also made genome editing mutants in the component protein that recognizes the 9580b482-17f5-4151-b80b-bf83c7deef23/293-4 00:58:48.128 --> 00:58:48.692 pin code. 9580b482-17f5-4151-b80b-bf83c7deef23/294-0 00:58:48.812 --> 00:58:54.822 And and in humans we see that there's elevation of the protein translation in 9580b482-17f5-4151-b80b-bf83c7deef23/294-1 00:58:54.822 --> 00:58:59.831 in human cells as well. So this machinery that we had identified 9580b482-17f5-4151-b80b-bf83c7deef23/294-2 00:58:59.831 --> 00:59:06.226 in zoofish appears to be conserved and it seems to to utilize similar elements and 9580b482-17f5-4151-b80b-bf83c7deef23/294-3 00:59:06.226 --> 00:59:08.692 we published this and of course. 9580b482-17f5-4151-b80b-bf83c7deef23/295-0 00:59:08.812 --> 00:59:13.279 This was celebrated with cake, as always. So around that time, 9580b482-17f5-4151-b80b-bf83c7deef23/295-1 00:59:13.279 --> 00:59:18.809 we also had some new students joining. Some of you may recognize Finn Lambert 9580b482-17f5-4151-b80b-bf83c7deef23/295-2 00:59:18.809 --> 00:59:23.773 here, who was in the 糖心TV. So the key work was done by Adreish and 9580b482-17f5-4151-b80b-bf83c7deef23/295-3 00:59:23.773 --> 00:59:27.389 Andreas, and Finn actually was part of the 糖心TV 9580b482-17f5-4151-b80b-bf83c7deef23/295-4 00:59:27.389 --> 00:59:28.452 Arab doctorate. 9580b482-17f5-4151-b80b-bf83c7deef23/296-0 00:59:28.532 --> 00:59:32.159 Program, which also you know I was able to to lead 9580b482-17f5-4151-b80b-bf83c7deef23/296-1 00:59:32.159 --> 00:59:37.919 first with Rob Cross and then with Mia and with the fantastic support of our PGR 9580b482-17f5-4151-b80b-bf83c7deef23/296-2 00:59:37.919 --> 00:59:41.190 team. So these are some of the students who I 9580b482-17f5-4151-b80b-bf83c7deef23/296-3 00:59:41.190 --> 00:59:47.092 went to to meet in Singapore a couple of years back and you recognize Selena here. 9580b482-17f5-4151-b80b-bf83c7deef23/297-0 00:59:47.572 --> 00:59:51.893 And there's Edgar, who was in my lab, and there's Paulina. 9580b482-17f5-4151-b80b-bf83c7deef23/297-1 00:59:51.893 --> 00:59:56.799 So in addition to my lab, it's been really nice to see these young 9580b482-17f5-4151-b80b-bf83c7deef23/297-2 00:59:56.799 --> 01:00:01.486 people on their journeys. So the pin code that we identified in 9580b482-17f5-4151-b80b-bf83c7deef23/297-3 01:00:01.486 --> 01:00:06.612 noodle is found not only in in the growth factor itself, but also in. 9580b482-17f5-4151-b80b-bf83c7deef23/298-0 01:00:07.252 --> 01:00:11.719 its inhibitor, its receptor, and intracellular components. So, 9580b482-17f5-4151-b80b-bf83c7deef23/298-1 01:00:11.719 --> 01:00:15.831 there's a shared pin code in all these proper components, 9580b482-17f5-4151-b80b-bf83c7deef23/298-2 01:00:15.831 --> 01:00:20.724 suggesting that they might be regulated together uh in some way. So, 9580b482-17f5-4151-b80b-bf83c7deef23/298-3 01:00:20.724 --> 01:00:26.679 we then try to understand how this works, and this is very recent work by Adminshka 9580b482-17f5-4151-b80b-bf83c7deef23/298-4 01:00:26.679 --> 01:00:26.892 and 9580b482-17f5-4151-b80b-bf83c7deef23/299-0 01:00:27.172 --> 01:00:31.127 Andreas again. So they looked at this mutant Y box one 9580b482-17f5-4151-b80b-bf83c7deef23/299-1 01:00:31.127 --> 01:00:36.089 where this left-sided expression of noodle is altered in the mutant. 9580b482-17f5-4151-b80b-bf83c7deef23/299-2 01:00:36.089 --> 01:00:41.554 So it becomes either right-sided or bilateral and what that means for these 9580b482-17f5-4151-b80b-bf83c7deef23/299-3 01:00:41.554 --> 01:00:45.797 for these embryos. So essentially that that French flag is 9580b482-17f5-4151-b80b-bf83c7deef23/299-4 01:00:45.797 --> 01:00:46.372 altered. 9580b482-17f5-4151-b80b-bf83c7deef23/300-0 01:00:46.412 --> 01:00:53.128 The pattern is altered in this way, and what that means is that the heart, 9580b482-17f5-4151-b80b-bf83c7deef23/300-1 01:00:53.128 --> 01:01:00.292 in addition to having the wrong position, and I'm trying to find my mouse here. 9580b482-17f5-4151-b80b-bf83c7deef23/301-0 01:01:02.492 --> 01:01:03.492 How do I? 9580b482-17f5-4151-b80b-bf83c7deef23/302-0 01:01:05.612 --> 01:01:11.420 Find my mouse off. There it is. So normally you would have blood flow 9580b482-17f5-4151-b80b-bf83c7deef23/302-1 01:01:11.420 --> 01:01:12.332 from the A. 9580b482-17f5-4151-b80b-bf83c7deef23/304-0 01:01:13.292 --> 01:01:17.202 There we go. So this is the fish part at about five 9580b482-17f5-4151-b80b-bf83c7deef23/304-1 01:01:17.202 --> 01:01:21.112 days. Um There's the atrium, there's the ventricle, 9580b482-17f5-4151-b80b-bf83c7deef23/304-2 01:01:21.112 --> 01:01:26.225 and here is the AV canal. You can see individual blood cells moving 9580b482-17f5-4151-b80b-bf83c7deef23/304-3 01:01:26.225 --> 01:01:29.835 through, and normally the valve would get shut. 9580b482-17f5-4151-b80b-bf83c7deef23/304-4 01:01:29.835 --> 01:01:32.692 But in these mutants, in the proteins. 9580b482-17f5-4151-b80b-bf83c7deef23/306-0 01:01:33.052 --> 01:01:38.385 Team that recognizes the pin code. You can see that the blood flows, 9580b482-17f5-4151-b80b-bf83c7deef23/306-1 01:01:38.385 --> 01:01:44.799 flows back and it flushes back and forth and it appears like we have a heart valve 9580b482-17f5-4151-b80b-bf83c7deef23/306-2 01:01:44.799 --> 01:01:48.972 defect and then Adnishka then went on to do analysis. 9580b482-17f5-4151-b80b-bf83c7deef23/307-0 01:01:48.972 --> 01:01:54.169 And this was work done together with Michael Smith and his group. 9580b482-17f5-4151-b80b-bf83c7deef23/307-1 01:01:54.169 --> 01:01:58.735 And actually this is very similar to human valve defects. 9580b482-17f5-4151-b80b-bf83c7deef23/307-2 01:01:58.735 --> 01:02:02.515 And so this was collaborative work that we did. 9580b482-17f5-4151-b80b-bf83c7deef23/307-3 01:02:02.515 --> 01:02:08.892 Jan Grocken helped us identify the PIN code. One way did the functional analysis 9580b482-17f5-4151-b80b-bf83c7deef23/308-0 01:02:08.972 --> 01:02:12.826 those elements. And Mike's let me help us with a lot of 9580b482-17f5-4151-b80b-bf83c7deef23/308-1 01:02:12.826 --> 01:02:17.436 the heart genesis analysis. So this element and this paper that we 9580b482-17f5-4151-b80b-bf83c7deef23/308-2 01:02:17.436 --> 01:02:21.496 found in is present in multiple components of the pathway, 9580b482-17f5-4151-b80b-bf83c7deef23/308-3 01:02:21.496 --> 01:02:25.212 and is crucial not only for positioning of the heart, 9580b482-17f5-4151-b80b-bf83c7deef23/308-4 01:02:25.212 --> 01:02:28.652 but also for for development of the and function. 9580b482-17f5-4151-b80b-bf83c7deef23/309-0 01:02:28.732 --> 01:02:35.032 Of the of the mouth. So and this is of course the cake that we 9580b482-17f5-4151-b80b-bf83c7deef23/309-1 01:02:35.032 --> 01:02:38.332 had following this. So this this. 9580b482-17f5-4151-b80b-bf83c7deef23/310-0 01:02:39.292 --> 01:02:44.550 This pin code that we found in in zebrafish noodles is crucial not only for 9580b482-17f5-4151-b80b-bf83c7deef23/310-1 01:02:44.550 --> 01:02:48.493 for zebrafish, it's found all the way to humans. Second, 9580b482-17f5-4151-b80b-bf83c7deef23/310-2 01:02:48.493 --> 01:02:54.028 this pin code is is shared by multiple components of the pathway noodle itself, 9580b482-17f5-4151-b80b-bf83c7deef23/310-3 01:02:54.028 --> 01:02:58.040 it's it's inhibitors, receptors and also the enzymes that 9580b482-17f5-4151-b80b-bf83c7deef23/310-4 01:02:58.040 --> 01:02:58.732 cleave it. 9580b482-17f5-4151-b80b-bf83c7deef23/311-0 01:02:58.772 --> 01:03:03.690 So all this builds on an initial transcriptional switch which actually 9580b482-17f5-4151-b80b-bf83c7deef23/311-1 01:03:03.690 --> 01:03:09.370 turns on synthesis of these RNAs and then these pin codes kick in and these allow 9580b482-17f5-4151-b80b-bf83c7deef23/311-2 01:03:09.370 --> 01:03:15.119 tuning of gene expression levels and this is crucial and it's also for sorting and 9580b482-17f5-4151-b80b-bf83c7deef23/311-3 01:03:15.119 --> 01:03:18.652 and transporting these signals to the right place. 9580b482-17f5-4151-b80b-bf83c7deef23/312-0 01:03:18.732 --> 01:03:23.194 OK, so they act at the right time. So this element that we identified 9580b482-17f5-4151-b80b-bf83c7deef23/312-1 01:03:23.194 --> 01:03:28.038 controls not only the distribution of the RNA, but also where it gets made, 9580b482-17f5-4151-b80b-bf83c7deef23/312-2 01:03:28.038 --> 01:03:31.862 how much gets made. And this is very crucial for patterning 9580b482-17f5-4151-b80b-bf83c7deef23/312-3 01:03:31.862 --> 01:03:35.176 of the embryo. So what happens if you have too much 9580b482-17f5-4151-b80b-bf83c7deef23/312-4 01:03:35.176 --> 01:03:36.132 model too soon? 9580b482-17f5-4151-b80b-bf83c7deef23/313-0 01:03:36.412 --> 01:03:40.300 And what happens is, so this is a little fish embryo at about 9580b482-17f5-4151-b80b-bf83c7deef23/313-1 01:03:40.300 --> 01:03:43.373 a day old. If you have too much noodle too soon, 9580b482-17f5-4151-b80b-bf83c7deef23/313-2 01:03:43.373 --> 01:03:48.202 so in our mutant where the RNA fails to get to the correct address and stays 9580b482-17f5-4151-b80b-bf83c7deef23/313-3 01:03:48.202 --> 01:03:51.150 stuck, you have too much noodle being made too 9580b482-17f5-4151-b80b-bf83c7deef23/313-4 01:03:51.150 --> 01:03:53.972 soon. And what happens there is that we have 9580b482-17f5-4151-b80b-bf83c7deef23/313-5 01:03:53.972 --> 01:03:56.292 very few embryonic progenitive cells. 9580b482-17f5-4151-b80b-bf83c7deef23/314-0 01:03:56.412 --> 01:03:59.815 Instead, you have a lot of extramurionic cells. 9580b482-17f5-4151-b80b-bf83c7deef23/314-1 01:03:59.815 --> 01:04:05.273 So what that means is you have a very small fetus and a very large placenta. 9580b482-17f5-4151-b80b-bf83c7deef23/314-2 01:04:05.273 --> 01:04:08.393 And of course this is not going to survive. 9580b482-17f5-4151-b80b-bf83c7deef23/314-3 01:04:08.393 --> 01:04:11.937 And this is where I'm the students who work here. 9580b482-17f5-4151-b80b-bf83c7deef23/314-4 01:04:11.937 --> 01:04:16.332 So Leo Wong and Becky Leach were the key people who did this. 9580b482-17f5-4151-b80b-bf83c7deef23/315-0 01:04:16.412 --> 01:04:21.724 You identified another mutant within this pathway where instead of having a single 9580b482-17f5-4151-b80b-bf83c7deef23/315-1 01:04:21.724 --> 01:04:26.268 layer of nuclei that formed the extra-ending neonic tissue, and again, 9580b482-17f5-4151-b80b-bf83c7deef23/315-2 01:04:26.268 --> 01:04:28.764 you know, because you can see how this 9580b482-17f5-4151-b80b-bf83c7deef23/315-3 01:04:28.764 --> 01:04:32.732 placenta-like structure forms in living embryos in real time, 9580b482-17f5-4151-b80b-bf83c7deef23/315-4 01:04:32.732 --> 01:04:36.252 we are having to do any invasive experiments, whereas. 9580b482-17f5-4151-b80b-bf83c7deef23/316-0 01:04:36.412 --> 01:04:39.338 You know, if you were bucking with a mammal or with 9580b482-17f5-4151-b80b-bf83c7deef23/316-1 01:04:39.338 --> 01:04:44.009 humans, you'd be doing very invasive work. So this allows us to study this process 9580b482-17f5-4151-b80b-bf83c7deef23/316-2 01:04:44.009 --> 01:04:47.498 in a very simplified system, but in vivo in real time as it's 9580b482-17f5-4151-b80b-bf83c7deef23/316-3 01:04:47.498 --> 01:04:50.424 happening. And these are the key people who did the 9580b482-17f5-4151-b80b-bf83c7deef23/316-4 01:04:50.424 --> 01:04:53.181 early work. And this has been continued with our 9580b482-17f5-4151-b80b-bf83c7deef23/316-5 01:04:53.181 --> 01:04:56.332 postdoc Heda, who I'm very pleased with one of the best 9580b482-17f5-4151-b80b-bf83c7deef23/317-0 01:04:56.412 --> 01:04:59.628 Talk award last week at the LA Nest symposium. 9580b482-17f5-4151-b80b-bf83c7deef23/317-1 01:04:59.628 --> 01:05:05.376 So she's looking at how membranes and the cytoskeletonal remodel perform this extra 9580b482-17f5-4151-b80b-bf83c7deef23/317-2 01:05:05.376 --> 01:05:10.714 embryonic cell type and our collaborators in this work are listed here and we 9580b482-17f5-4151-b80b-bf83c7deef23/317-3 01:05:10.714 --> 01:05:12.972 continue to work on this problem. 9580b482-17f5-4151-b80b-bf83c7deef23/318-0 01:05:12.972 --> 01:05:19.554 So we've been looking at these mechanisms that control cell fate, how tissues form, 9580b482-17f5-4151-b80b-bf83c7deef23/318-1 01:05:19.554 --> 01:05:25.195 how signals are distributed. So these things happen at the right place, 9580b482-17f5-4151-b80b-bf83c7deef23/318-2 01:05:25.195 --> 01:05:31.150 right time, mostly in the embryo, but a lot of our our current work is also 9580b482-17f5-4151-b80b-bf83c7deef23/318-3 01:05:31.150 --> 01:05:32.012 looking at. 9580b482-17f5-4151-b80b-bf83c7deef23/319-0 01:05:32.132 --> 01:05:36.828 Oh goodness, there we go. So we're also looking at the germline and 9580b482-17f5-4151-b80b-bf83c7deef23/319-1 01:05:36.828 --> 01:05:42.423 I'm showing you a beautiful movie taken by Elias Zalka where he's looking at how 9580b482-17f5-4151-b80b-bf83c7deef23/319-2 01:05:42.423 --> 01:05:46.290 the germline, the cells that will give rise to the next 9580b482-17f5-4151-b80b-bf83c7deef23/319-3 01:05:46.290 --> 01:05:50.572 generation, how do they get, how do they form and how do you? 9580b482-17f5-4151-b80b-bf83c7deef23/320-0 01:05:50.572 --> 01:05:56.118 How do RNAs control this process? So this is work that Andreas and Maria 9580b482-17f5-4151-b80b-bf83c7deef23/320-1 01:05:56.118 --> 01:06:01.588 have been trying to work out. Again, using the power of live imaging in 9580b482-17f5-4151-b80b-bf83c7deef23/320-2 01:06:01.588 --> 01:06:07.893 zebrafish, manipulating the cytoskeleton, looking at many of these mutants that we 9580b482-17f5-4151-b80b-bf83c7deef23/320-3 01:06:07.893 --> 01:06:10.172 have generated over the years. 9580b482-17f5-4151-b80b-bf83c7deef23/321-0 01:06:10.332 --> 01:06:14.702 Understand how the GM line seems at the right place, right time. 9580b482-17f5-4151-b80b-bf83c7deef23/321-1 01:06:14.702 --> 01:06:19.810 How do you give rise to the next generation? OK, and we're also looking at. 9580b482-17f5-4151-b80b-bf83c7deef23/321-2 01:06:19.810 --> 01:06:23.844 So there's Andreas. In addition to establishing imaging and 9580b482-17f5-4151-b80b-bf83c7deef23/321-3 01:06:23.844 --> 01:06:27.003 the tools, he's also been crucial for training 9580b482-17f5-4151-b80b-bf83c7deef23/321-4 01:06:27.003 --> 01:06:29.692 people not only in my own lab, but also. 9580b482-17f5-4151-b80b-bf83c7deef23/322-0 01:06:29.852 --> 01:06:34.558 All the visitors that we've had through the years, here he is with Azan, 9580b482-17f5-4151-b80b-bf83c7deef23/322-1 01:06:34.558 --> 01:06:39.651 who is a visitor from Qatar University who came to us this summer to learn how 9580b482-17f5-4151-b80b-bf83c7deef23/322-2 01:06:39.651 --> 01:06:44.679 to image and he's been very helpful. So Andreas is is looking at how does the 9580b482-17f5-4151-b80b-bf83c7deef23/322-3 01:06:44.679 --> 01:06:48.225 germline get established, how does it form and they're 9580b482-17f5-4151-b80b-bf83c7deef23/322-4 01:06:48.225 --> 01:06:49.772 collaborating with with. 9580b482-17f5-4151-b80b-bf83c7deef23/323-0 01:06:49.852 --> 01:06:56.375 at the Engineering Department at Cambridge University and the Rouse who's 9580b482-17f5-4151-b80b-bf83c7deef23/323-1 01:06:56.375 --> 01:07:03.426 a joint student and they're using both experimental and mathematical approaches 9580b482-17f5-4151-b80b-bf83c7deef23/323-2 01:07:03.426 --> 01:07:09.772 to understand how the shape of forces or free of cytosol influences the 9580b482-17f5-4151-b80b-bf83c7deef23/324-0 01:07:09.892 --> 01:07:14.652 Distribution of these granules that are important for forming the germline in the 9580b482-17f5-4151-b80b-bf83c7deef23/324-1 01:07:14.652 --> 01:07:17.263 next generation. And last but not the least, 9580b482-17f5-4151-b80b-bf83c7deef23/324-2 01:07:17.263 --> 01:07:21.849 we're still very interested in how does the egg know how to put its head and a 9580b482-17f5-4151-b80b-bf83c7deef23/324-3 01:07:21.849 --> 01:07:26.260 key structure in this in early oocytes. In all vertebrates at early stages, 9580b482-17f5-4151-b80b-bf83c7deef23/324-4 01:07:26.260 --> 01:07:29.452 there's a structure called the Balbiani body which is. 9580b482-17f5-4151-b80b-bf83c7deef23/325-0 01:07:29.492 --> 01:07:33.603 Discovered 160 years ago, we don't really understand what it does 9580b482-17f5-4151-b80b-bf83c7deef23/325-1 01:07:33.603 --> 01:07:37.092 and how it functions. And many of the components in the 9580b482-17f5-4151-b80b-bf83c7deef23/325-2 01:07:37.092 --> 01:07:42.138 biogenic body then get distributed either to the germ plasm or similar to neuron 9580b482-17f5-4151-b80b-bf83c7deef23/325-3 01:07:42.138 --> 01:07:45.315 get distributed to specific locations in the eggs. 9580b482-17f5-4151-b80b-bf83c7deef23/325-4 01:07:45.315 --> 01:07:49.052 So we basically moved the clock back. We're now going back. 9580b482-17f5-4151-b80b-bf83c7deef23/326-0 01:07:49.132 --> 01:07:53.647 to the very beginning, early stages of when eggs are made to 9580b482-17f5-4151-b80b-bf83c7deef23/326-1 01:07:53.647 --> 01:07:59.493 understand how these RNAs get to where they are and how they function later on 9580b482-17f5-4151-b80b-bf83c7deef23/326-2 01:07:59.493 --> 01:08:04.822 in in the egg and the embryo. We're also taking a comparative approach. 9580b482-17f5-4151-b80b-bf83c7deef23/326-3 01:08:04.822 --> 01:08:08.892 Our newest model organism is the mangrove kidney fish. 9580b482-17f5-4151-b80b-bf83c7deef23/327-0 01:08:08.972 --> 01:08:13.608 And this is work being done by a new student in the lab. 9580b482-17f5-4151-b80b-bf83c7deef23/327-1 01:08:13.608 --> 01:08:20.116 And together we hope to understand the basis of how oocytes develop and how the 9580b482-17f5-4151-b80b-bf83c7deef23/327-2 01:08:20.116 --> 01:08:24.996 Indianic axis forms. And perhaps I'll be able to go back to 9580b482-17f5-4151-b80b-bf83c7deef23/327-3 01:08:24.996 --> 01:08:28.412 address that original question that I had. 9580b482-17f5-4151-b80b-bf83c7deef23/328-0 01:08:28.492 --> 01:08:31.297 What is normal RNA doing in the egg anyway? 9580b482-17f5-4151-b80b-bf83c7deef23/328-1 01:08:31.297 --> 01:08:35.121 And what does that have to do with how you put put the egg? 9580b482-17f5-4151-b80b-bf83c7deef23/328-2 01:08:35.121 --> 01:08:39.711 So how is this relevant? Well, the balbani body is present in humans as 9580b482-17f5-4151-b80b-bf83c7deef23/328-3 01:08:39.711 --> 01:08:42.133 well. And of course we can't do these 9580b482-17f5-4151-b80b-bf83c7deef23/328-4 01:08:42.133 --> 01:08:47.041 manipulations in in human research, but the fish is very accessible to these 9580b482-17f5-4151-b80b-bf83c7deef23/328-5 01:08:47.041 --> 01:08:48.252 and we have all the 9580b482-17f5-4151-b80b-bf83c7deef23/329-0 01:08:48.372 --> 01:08:51.646 now. So I'll give you some of the the lab 9580b482-17f5-4151-b80b-bf83c7deef23/329-1 01:08:51.646 --> 01:08:55.700 outings that we've had over the years here at work. 9580b482-17f5-4151-b80b-bf83c7deef23/329-2 01:08:55.700 --> 01:09:01.936 We can see Christmas over the years, some lab trips to the to the Maldon Hills, 9580b482-17f5-4151-b80b-bf83c7deef23/329-3 01:09:01.936 --> 01:09:08.172 Camembert Castle, Coventry Cathedral, and of course we're a lab that eats well. 9580b482-17f5-4151-b80b-bf83c7deef23/330-0 01:09:08.172 --> 01:09:13.436 And here are all the talented people who make this possible. 9580b482-17f5-4151-b80b-bf83c7deef23/330-1 01:09:13.436 --> 01:09:20.511 So here are the students, their examiners, collaborators without whom all of this 9580b482-17f5-4151-b80b-bf83c7deef23/330-2 01:09:20.511 --> 01:09:25.948 would be impossible. The many trainees who've come through the 9580b482-17f5-4151-b80b-bf83c7deef23/330-3 01:09:25.948 --> 01:09:27.932 lab over the years and. 9580b482-17f5-4151-b80b-bf83c7deef23/331-0 01:09:28.012 --> 01:09:30.637 You know, I I also want to acknowledge the 9580b482-17f5-4151-b80b-bf83c7deef23/331-1 01:09:30.637 --> 01:09:33.385 community, not just here at work and the UK, 9580b482-17f5-4151-b80b-bf83c7deef23/331-2 01:09:33.385 --> 01:09:37.781 but also throughout the world, who've been very supportive of our work, 9580b482-17f5-4151-b80b-bf83c7deef23/331-3 01:09:37.781 --> 01:09:41.200 very generous in sharing their relations. And you know, 9580b482-17f5-4151-b80b-bf83c7deef23/331-4 01:09:41.200 --> 01:09:45.656 when I started out as a student, I never learned that I would one day be 9580b482-17f5-4151-b80b-bf83c7deef23/331-5 01:09:45.656 --> 01:09:47.732 the president of the international 9580b482-17f5-4151-b80b-bf83c7deef23/332-0 01:09:47.852 --> 01:09:53.239 Society. I just got elected last month. This is a society with about 1100 overall 9580b482-17f5-4151-b80b-bf83c7deef23/332-1 01:09:53.239 --> 01:09:57.838 members in 60 labs worldwide. So this has really been quite a journey 9580b482-17f5-4151-b80b-bf83c7deef23/332-2 01:09:57.838 --> 01:10:02.896 and I'm really very pleased that that I've had all these people that I could 9580b482-17f5-4151-b80b-bf83c7deef23/332-3 01:10:02.896 --> 01:10:05.852 lean on throughout every stage of my career. 9580b482-17f5-4151-b80b-bf83c7deef23/333-0 01:10:06.052 --> 01:10:12.423 And I should also leave you with the names of all the people who've actually 9580b482-17f5-4151-b80b-bf83c7deef23/333-1 01:10:12.423 --> 01:10:16.147 done all the work, the funders in Singapore, 9580b482-17f5-4151-b80b-bf83c7deef23/333-2 01:10:16.147 --> 01:10:20.532 and I've got many, many collaborators and of course. 9580b482-17f5-4151-b80b-bf83c7deef23/334-0 01:10:21.452 --> 01:10:26.889 糖心TV there you know we are continuing to work on these the you know there are 9580b482-17f5-4151-b80b-bf83c7deef23/334-1 01:10:26.889 --> 01:10:30.044 many, many collaborators not just in Singapore 9580b482-17f5-4151-b80b-bf83c7deef23/334-2 01:10:30.044 --> 01:10:35.280 but worldwide and and and at 糖心TV the main facilities most of all the fish 9580b482-17f5-4151-b80b-bf83c7deef23/334-3 01:10:35.280 --> 01:10:40.180 facility but also the imaging, I mean the outstanding imaging facilities 9580b482-17f5-4151-b80b-bf83c7deef23/334-4 01:10:40.180 --> 01:10:41.052 that we have. 9580b482-17f5-4151-b80b-bf83c7deef23/335-0 01:10:41.052 --> 01:10:45.925 Potomax and the others. And you know, we were very fortunate to have next door 9580b482-17f5-4151-b80b-bf83c7deef23/335-1 01:10:45.925 --> 01:10:50.860 and and Teresa in particular has been like really superb in in helping us every 9580b482-17f5-4151-b80b-bf83c7deef23/335-2 01:10:50.860 --> 01:10:54.314 step of the way. Bernardo helped us with imaging men in 9580b482-17f5-4151-b80b-bf83c7deef23/335-3 01:10:54.314 --> 01:10:58.878 the in the early years as well. So all these people and of course all our 9580b482-17f5-4151-b80b-bf83c7deef23/335-4 01:10:58.878 --> 01:11:00.852 funders over the years, we were. 9580b482-17f5-4151-b80b-bf83c7deef23/336-0 01:11:00.892 --> 01:11:06.082 and DBSRC have supported my work and in the early stages of the Welcome Upwork 9580b482-17f5-4151-b80b-bf83c7deef23/336-1 01:11:06.082 --> 01:11:09.695 Quantitative Biomedicine program also the seed grants. 9580b482-17f5-4151-b80b-bf83c7deef23/336-2 01:11:09.695 --> 01:11:14.754 You know we don't see enough of these anymore and it would be really nice to 9580b482-17f5-4151-b80b-bf83c7deef23/336-3 01:11:14.754 --> 01:11:19.615 see those kinds of small grants that would then allow you to to start new 9580b482-17f5-4151-b80b-bf83c7deef23/336-4 01:11:19.615 --> 01:11:20.732 projects and then 9580b482-17f5-4151-b80b-bf83c7deef23/337-0 01:11:20.732 --> 01:11:25.177 Take them to the next level, the medical and life sciences research 9580b482-17f5-4151-b80b-bf83c7deef23/337-1 01:11:25.177 --> 01:11:28.315 fund, the many doctoral programs at work and of 9580b482-17f5-4151-b80b-bf83c7deef23/337-2 01:11:28.315 --> 01:11:28.772 course. 9580b482-17f5-4151-b80b-bf83c7deef23/339-0 01:11:29.772 --> 01:11:35.197 All of you and I I want to give a special shout to all the my colleagues on the 9580b482-17f5-4151-b80b-bf83c7deef23/339-1 01:11:35.197 --> 01:11:39.198 IBRB third floor. And you know we have this great lab rats 9580b482-17f5-4151-b80b-bf83c7deef23/339-2 01:11:39.198 --> 01:11:44.420 team which is very competitive and we we like to to compete in the tri-grade 9580b482-17f5-4151-b80b-bf83c7deef23/339-3 01:11:44.420 --> 01:11:47.132 events and where's that cup? It's going. 9580b482-17f5-4151-b80b-bf83c7deef23/340-0 01:11:47.732 --> 01:11:52.205 OK. We're very proud of our, our, our tri-made binning cups. 9580b482-17f5-4151-b80b-bf83c7deef23/340-1 01:11:52.205 --> 01:11:56.899 So come see that on the third floor when you have a chance. So, 9580b482-17f5-4151-b80b-bf83c7deef23/340-2 01:11:56.899 --> 01:12:01.152 so thank you very much. It's been a pleasure to work with 9580b482-17f5-4151-b80b-bf83c7deef23/340-3 01:12:01.152 --> 01:12:06.652 everyone and I look forward to many more years of of trying to figure out. 9580b482-17f5-4151-b80b-bf83c7deef23/341-0 01:12:06.892 --> 01:12:10.252 Are the animals how to put the head? So thank you. 9580b482-17f5-4151-b80b-bf83c7deef23/343-0 01:12:19.812 --> 01:12:25.418 Fantastic and inspiring talk. We've got time for a couple of questions. 9580b482-17f5-4151-b80b-bf83c7deef23/343-1 01:12:25.418 --> 01:12:31.492 I'm going to take Dean's prerogative to start off with the first question and 9580b482-17f5-4151-b80b-bf83c7deef23/343-2 01:12:31.492 --> 01:12:35.852 it's really I think I took three things away from your. 9580b482-17f5-4151-b80b-bf83c7deef23/344-0 01:12:36.292 --> 01:12:40.637 You know, firstly the complexity, the depth and the excellence of the 9580b482-17f5-4151-b80b-bf83c7deef23/344-1 01:12:40.637 --> 01:12:45.354 science that you're doing. Secondly, the collaboration of the networks came 9580b482-17f5-4151-b80b-bf83c7deef23/344-2 01:12:45.354 --> 01:12:50.196 through really powerful. And thirdly, the role that you've played as a mentor 9580b482-17f5-4151-b80b-bf83c7deef23/344-3 01:12:50.196 --> 01:12:53.920 for the generation of scientists that that will follow you. 9580b482-17f5-4151-b80b-bf83c7deef23/344-4 01:12:53.920 --> 01:12:56.092 So picking the middle one of those. 9580b482-17f5-4151-b80b-bf83c7deef23/345-0 01:12:56.252 --> 01:13:01.062 Around collaboration is how have you managed to create and sustain such 9580b482-17f5-4151-b80b-bf83c7deef23/345-1 01:13:01.062 --> 01:13:06.406 networks and what pace would you have for colleagues in terms of emulating like 9580b482-17f5-4151-b80b-bf83c7deef23/345-2 01:13:06.406 --> 01:13:09.479 that? Yeah. So in the early years, of course, 9580b482-17f5-4151-b80b-bf83c7deef23/345-3 01:13:09.479 --> 01:13:14.890 collaboration is happening because of the environment I was in, you know, Chris, 9580b482-17f5-4151-b80b-bf83c7deef23/345-4 01:13:14.890 --> 01:13:16.092 as soon as he saw. 9580b482-17f5-4151-b80b-bf83c7deef23/346-0 01:13:16.252 --> 01:13:20.799 Our left side of gene expression who got on the phone because that's what you did 9580b482-17f5-4151-b80b-bf83c7deef23/346-1 01:13:20.799 --> 01:13:24.848 those days and talk to people who are working on on the mouse and so on. 9580b482-17f5-4151-b80b-bf83c7deef23/346-2 01:13:24.848 --> 01:13:28.563 And we could, you know, that just happened because of where I was. 9580b482-17f5-4151-b80b-bf83c7deef23/346-3 01:13:28.563 --> 01:13:32.556 And then I initiated the work on zebrafish and then carried that on and 9580b482-17f5-4151-b80b-bf83c7deef23/346-4 01:13:32.556 --> 01:13:35.772 then worked collaboratively with the people in the state. 9580b482-17f5-4151-b80b-bf83c7deef23/348-0 01:13:35.852 --> 01:13:40.102 And also in Singapore to take that forward. And of course, again, 9580b482-17f5-4151-b80b-bf83c7deef23/348-1 01:13:40.102 --> 01:13:45.189 the environment played a role because I was in this institute which forteously 9580b482-17f5-4151-b80b-bf83c7deef23/348-2 01:13:45.189 --> 01:13:50.469 had people who were working as advisors who could then put me in touch with that. 9580b482-17f5-4151-b80b-bf83c7deef23/348-3 01:13:50.469 --> 01:13:55.492 So I think it's really a combination of one is we cannot do everything alone. 9580b482-17f5-4151-b80b-bf83c7deef23/350-0 01:13:55.692 --> 01:14:00.736 It was true then, all you know so now, and you do need to seek out and find 9580b482-17f5-4151-b80b-bf83c7deef23/350-1 01:14:00.736 --> 01:14:05.846 people who can add value to your own work, really things that you cannot do. 9580b482-17f5-4151-b80b-bf83c7deef23/350-2 01:14:05.846 --> 01:14:10.292 And together you solve more than you would never be able to alone. 9580b482-17f5-4151-b80b-bf83c7deef23/351-0 01:14:10.332 --> 01:14:15.371 And and I guess these days you do need to be interdisciplinary. 9580b482-17f5-4151-b80b-bf83c7deef23/351-1 01:14:15.371 --> 01:14:18.992 Now I come from a classical zoology training. 9580b482-17f5-4151-b80b-bf83c7deef23/351-2 01:14:18.992 --> 01:14:22.693 What do I know about simulations and modeling? 9580b482-17f5-4151-b80b-bf83c7deef23/351-3 01:14:22.693 --> 01:14:28.519 So I do see these this expertise out and that has really worked and yeah, 9580b482-17f5-4151-b80b-bf83c7deef23/351-4 01:14:28.519 --> 01:14:30.172 I mean circumstances. 9580b482-17f5-4151-b80b-bf83c7deef23/352-0 01:14:30.172 --> 01:14:34.020 Not knowing enough. And then of course the environment. 9580b482-17f5-4151-b80b-bf83c7deef23/352-1 01:14:34.020 --> 01:14:38.968 And 糖心TV's a great place to do collaborative interdisciplinary work, 9580b482-17f5-4151-b80b-bf83c7deef23/352-2 01:14:38.968 --> 01:14:44.465 I have to say. Yeah, great. Thank you. So we'll open up for anyone that has any 9580b482-17f5-4151-b80b-bf83c7deef23/352-3 01:14:44.465 --> 01:14:46.252 questions in the audience. 9580b482-17f5-4151-b80b-bf83c7deef23/353-0 01:14:47.492 --> 01:14:53.212 Not sure if Claire or colleagues consider that Leslie has one Leslie. 9580b482-17f5-4151-b80b-bf83c7deef23/355-0 01:14:54.332 --> 01:14:57.711 Just because there's been a non my amendments, 9580b482-17f5-4151-b80b-bf83c7deef23/355-1 01:14:57.711 --> 01:15:03.246 don't expect me to ask the question, but and I hate to say this when you are 9580b482-17f5-4151-b80b-bf83c7deef23/355-2 01:15:03.246 --> 01:15:07.415 just the president-elect of the executive prime. However, 9580b482-17f5-4151-b80b-bf83c7deef23/355-3 01:15:07.415 --> 01:15:12.878 I'm aware that obviously the government has been expansion of the number of 9580b482-17f5-4151-b80b-bf83c7deef23/355-4 01:15:12.878 --> 01:15:13.812 publications. 9580b482-17f5-4151-b80b-bf83c7deef23/356-0 01:15:13.932 --> 01:15:20.341 In the last decade using zebrafish models, but zebrafish and tropical fish. 9580b482-17f5-4151-b80b-bf83c7deef23/356-1 01:15:20.341 --> 01:15:25.738 So from a climate perspective, maintaining them costs more than 9580b482-17f5-4151-b80b-bf83c7deef23/356-2 01:15:25.738 --> 01:15:29.532 maintaining coal to fish. So my question is. 9580b482-17f5-4151-b80b-bf83c7deef23/357-0 01:15:29.532 --> 01:15:34.107 Why? Why have we not identified the more 9580b482-17f5-4151-b80b-bf83c7deef23/357-1 01:15:34.107 --> 01:15:42.364 climate friendly alternative? No, no, no. I'll just join another society. 9580b482-17f5-4151-b80b-bf83c7deef23/357-2 01:15:42.364 --> 01:15:44.372 Easier to do that. 9580b482-17f5-4151-b80b-bf83c7deef23/358-0 01:15:44.892 --> 01:15:49.630 Actually, when we go to the fish meetings, we welcome other fish as well. 9580b482-17f5-4151-b80b-bf83c7deef23/358-1 01:15:49.630 --> 01:15:53.408 So we recently started working on this mangrove killifish, 9580b482-17f5-4151-b80b-bf83c7deef23/358-2 01:15:53.408 --> 01:15:58.658 which has a wide geographical range and is extremely tolerant of of a temperature 9580b482-17f5-4151-b80b-bf83c7deef23/358-3 01:15:58.658 --> 01:16:01.795 range. So it grows in mangroves all the way from 9580b482-17f5-4151-b80b-bf83c7deef23/358-4 01:16:01.795 --> 01:16:03.332 freshwater to the ocean. 9580b482-17f5-4151-b80b-bf83c7deef23/359-0 01:16:04.892 --> 01:16:09.906 Wide tolerance and this is our climate change model going into the future. 9580b482-17f5-4151-b80b-bf83c7deef23/359-1 01:16:09.906 --> 01:16:13.248 And because we just know so much about zebrafish, 9580b482-17f5-4151-b80b-bf83c7deef23/359-2 01:16:13.248 --> 01:16:18.529 we're using that for comparative studies and use that as sort of a foundation. 9580b482-17f5-4151-b80b-bf83c7deef23/359-3 01:16:18.529 --> 01:16:21.805 But yes, I fully appreciate your question and we 9580b482-17f5-4151-b80b-bf83c7deef23/359-4 01:16:21.805 --> 01:16:24.612 are thinking about this, so going forward. 9580b482-17f5-4151-b80b-bf83c7deef23/360-0 01:16:24.812 --> 01:16:29.551 We are going to look at, you know, what does climate change do to the body 9580b482-17f5-4151-b80b-bf83c7deef23/360-1 01:16:29.551 --> 01:16:32.331 plan, to the reproductive system? You know, 9580b482-17f5-4151-b80b-bf83c7deef23/360-2 01:16:32.331 --> 01:16:36.122 fish are the most important source of protein in the world, 9580b482-17f5-4151-b80b-bf83c7deef23/360-3 01:16:36.122 --> 01:16:40.166 and all these changes are impacting fish populations worldwide. 9580b482-17f5-4151-b80b-bf83c7deef23/360-4 01:16:40.166 --> 01:16:44.652 And we want to look at how these extremophiles are somehow able to to. 9580b482-17f5-4151-b80b-bf83c7deef23/361-0 01:16:44.852 --> 01:16:50.013 Take this on board and still maintain their reproductive capacity and maintain 9580b482-17f5-4151-b80b-bf83c7deef23/361-1 01:16:50.013 --> 01:16:50.732 continuity. 9580b482-17f5-4151-b80b-bf83c7deef23/362-0 01:16:52.812 --> 01:16:57.252 So hopefully learning more from a comparative approach, yeah. 9580b482-17f5-4151-b80b-bf83c7deef23/363-0 01:16:58.892 --> 01:17:02.756 Lovely. Thank you, Leslie. I'm not seeing hands raised elsewhere. 9580b482-17f5-4151-b80b-bf83c7deef23/363-1 01:17:02.756 --> 01:17:06.504 We're getting clash. I think we've got one more. Yeah, judging. 9580b482-17f5-4151-b80b-bf83c7deef23/363-2 01:17:06.504 --> 01:17:11.012 I'm going to bring them out just for the help of the people that are online. 9580b482-17f5-4151-b80b-bf83c7deef23/364-0 01:17:16.292 --> 01:17:24.787 Thanks for that. You know, relationship. But is more and more. Thankfully, 9580b482-17f5-4151-b80b-bf83c7deef23/364-1 01:17:24.787 --> 01:17:28.412 as you say about climate change. 9580b482-17f5-4151-b80b-bf83c7deef23/366-0 01:17:29.052 --> 01:17:37.639 And because you know the heart of the is this idea that you have these these 9580b482-17f5-4151-b80b-bf83c7deef23/366-1 01:17:37.639 --> 01:17:43.772 proteins that connect together to form a physical and. 9580b482-17f5-4151-b80b-bf83c7deef23/367-0 01:17:44.492 --> 01:17:49.185 And I'm just wondering what happened when you look at killfish, 9580b482-17f5-4151-b80b-bf83c7deef23/367-1 01:17:49.185 --> 01:17:53.879 these different temperature, what happens to this in the works. 9580b482-17f5-4151-b80b-bf83c7deef23/367-2 01:17:53.879 --> 01:17:58.425 That is something that that that May has starting to explore. 9580b482-17f5-4151-b80b-bf83c7deef23/367-3 01:17:58.425 --> 01:18:03.852 She's looking at what happens to germline RNA complexes and yeah, that's. 9580b482-17f5-4151-b80b-bf83c7deef23/369-0 01:18:03.852 --> 01:18:07.201 In fact, she had a summer high school student work 9580b482-17f5-4151-b80b-bf83c7deef23/369-1 01:18:07.201 --> 01:18:10.354 with her looking at two different temperatures. 9580b482-17f5-4151-b80b-bf83c7deef23/369-2 01:18:10.354 --> 01:18:12.652 So this is ongoing right now. Yeah. 9580b482-17f5-4151-b80b-bf83c7deef23/370-0 01:18:13.532 --> 01:18:13.812 Thank you. 9580b482-17f5-4151-b80b-bf83c7deef23/372-0 01:18:22.332 --> 01:18:29.199 I think I think that brings us up to time. We've got a very excited on the list that 9580b482-17f5-4151-b80b-bf83c7deef23/372-1 01:18:29.199 --> 01:18:34.450 I'm going to present to you shortly, but just for you, you know, 9580b482-17f5-4151-b80b-bf83c7deef23/372-2 01:18:34.450 --> 01:18:38.812 many congratulations. Thank you. Thank you very much. 9580b482-17f5-4151-b80b-bf83c7deef23/373-0 01:18:39.012 --> 01:18:40.292 It is yours. 9580b482-17f5-4151-b80b-bf83c7deef23/376-0 01:18:47.932 --> 01:18:55.632 You've been waiting for. Thank you. It's very beautiful all the same. 9580b482-17f5-4151-b80b-bf83c7deef23/376-1 01:18:55.632 --> 01:18:56.732 Thank you. 9580b482-17f5-4151-b80b-bf83c7deef23/379-0 01:19:08.252 --> 01:19:08.372 OK. 9580b482-17f5-4151-b80b-bf83c7deef23/380-0 01:19:11.212 --> 01:19:11.332 You. 9580b482-17f5-4151-b80b-bf83c7deef23/382-0 01:19:12.732 --> 01:19:16.412 Yeah, yeah.