Smith, Leisha: It's a pleasure to be hosting this lecture here today for for Karuna. 9580b482-17f5-4151-b80b-bf83c7deef23/135-2
Smith, Leisha: For people I've had the opportunity to meet, I'm Gavin Perkins, 9580b482-17f5-4151-b80b-bf83c7deef23/135-3
Smith, Leisha: I'm the Dean of Medicine. 9580b482-17f5-4151-b80b-bf83c7deef23/137-0
Smith, Leisha: Here at Warwick and it really is a fantastic opportunity for celebration. 9580b482-17f5-4151-b80b-bf83c7deef23/137-1
Smith, Leisha: Professor Karina Sampath, family, friends and colleagues, 9580b482-17f5-4151-b80b-bf83c7deef23/137-2
Smith, Leisha: welcome to this inaugural lecture. The inaugural lecture is actually 9580b482-17f5-4151-b80b-bf83c7deef23/137-3
Smith, Leisha: something really important, especially represents a key milestone in 9580b482-17f5-4151-b80b-bf83c7deef23/137-4
Smith, Leisha: an academic. 9580b482-17f5-4151-b80b-bf83c7deef23/139-0
Smith, Leisha: Career signifying their promotion to professor. 9580b482-17f5-4151-b80b-bf83c7deef23/139-1
Smith, Leisha: And that promotion to professor is more because it's not just a change in style. 9580b482-17f5-4151-b80b-bf83c7deef23/139-2
Smith, Leisha: It's not something that's bestowed lightly. 9580b482-17f5-4151-b80b-bf83c7deef23/139-3
Smith, Leisha: It's a meticulous process of assessment that someone. 9580b482-17f5-4151-b80b-bf83c7deef23/140-0
Smith, Leisha: Is assessed with their their peers, and it's a profound marker of the respect 9580b482-17f5-4151-b80b-bf83c7deef23/140-1
Smith, Leisha: and admiration that people have through the mistake of the title of assessment, 9580b482-17f5-4151-b80b-bf83c7deef23/140-2
Smith, Leisha: which is a truly exceptional colleague. 9580b482-17f5-4151-b80b-bf83c7deef23/141-0
Smith, Leisha: This honour acknowledges your remarkable contributions and the valuable impact you 9580b482-17f5-4151-b80b-bf83c7deef23/141-1
Smith, Leisha: have not only in your field, but also to the broader higher education 9580b482-17f5-4151-b80b-bf83c7deef23/141-2
Smith, Leisha: sector. It also sets high expectations for the 9580b482-17f5-4151-b80b-bf83c7deef23/141-3
Smith, Leisha: future contributions holding the title of Professor. 9580b482-17f5-4151-b80b-bf83c7deef23/142-0
Smith, Leisha: It implies the responsibility to uphold and champion the principles of 9580b482-17f5-4151-b80b-bf83c7deef23/142-1
Smith, Leisha: collegiality, academic freedom, and the relentless pursuit of knowledge 9580b482-17f5-4151-b80b-bf83c7deef23/142-2
Smith, Leisha: and practice for the betterment of society. 9580b482-17f5-4151-b80b-bf83c7deef23/142-3
Smith, Leisha: We're incredibly fortunate to have Professor Grudius Sampath as one of our 9580b482-17f5-4151-b80b-bf83c7deef23/142-4
Smith, Leisha: colleagues. 9580b482-17f5-4151-b80b-bf83c7deef23/144-0
Smith, Leisha: Her pioneering work over the last 30 years on the fundamental mechanisms that 9580b482-17f5-4151-b80b-bf83c7deef23/144-1
Smith, Leisha: control development and differentiation has seen her work around the world of 9580b482-17f5-4151-b80b-bf83c7deef23/144-2
Smith, Leisha: price making Warwick a home in 2014, your awakening dedication and 9580b482-17f5-4151-b80b-bf83c7deef23/144-3
Smith, Leisha: achievements of service as an inspiration to the wider community. 9580b482-17f5-4151-b80b-bf83c7deef23/146-0
Smith, Leisha: This honour acknowledges your remarkable achievements and the valuable impact that 9580b482-17f5-4151-b80b-bf83c7deef23/146-1
Smith, Leisha: you made on your field at the border landscape in higher education. Bruner, 9580b482-17f5-4151-b80b-bf83c7deef23/146-2
Smith, Leisha: please share where is your noble lecture. How does an egg know where to put the 9580b482-17f5-4151-b80b-bf83c7deef23/146-3
Smith, Leisha: head? 9580b482-17f5-4151-b80b-bf83c7deef23/147-0
Smith, Leisha: Thank you, Kevin. 9580b482-17f5-4151-b80b-bf83c7deef23/148-0
Smith, Leisha: Thank you all for coming today. And to everyone who's online, 9580b482-17f5-4151-b80b-bf83c7deef23/148-1
Smith, Leisha: thank you very much for joining this lecture. 9580b482-17f5-4151-b80b-bf83c7deef23/148-2
Smith, Leisha: I have posted this a couple of times, so in in all fairness, it's, you know, 9580b482-17f5-4151-b80b-bf83c7deef23/148-3
Smith, Leisha: it's my fault this is happening today. 9580b482-17f5-4151-b80b-bf83c7deef23/149-0
Smith, Leisha: But thank you all the same. So I was told that this talk is more 9580b482-17f5-4151-b80b-bf83c7deef23/149-1
Smith, Leisha: about, you know, the journey and how I got to where I am. 9580b482-17f5-4151-b80b-bf83c7deef23/149-2
Smith, Leisha: So there'll be a little bit of science and a lot of, you know, 9580b482-17f5-4151-b80b-bf83c7deef23/149-3
Smith, Leisha: how things came about and and how. 9580b482-17f5-4151-b80b-bf83c7deef23/150-0
Smith, Leisha: We are where we are today. So I've been interested in in the 9580b482-17f5-4151-b80b-bf83c7deef23/150-1
Smith, Leisha: fundamental mechanisms that make the vertebrate body plan. 9580b482-17f5-4151-b80b-bf83c7deef23/150-2
Smith, Leisha: And we care about this because 6% of all newborns globally have a birth defect 9580b482-17f5-4151-b80b-bf83c7deef23/150-3
Smith, Leisha: when they're born and we still don't fully understand what goes wrong. 9580b482-17f5-4151-b80b-bf83c7deef23/151-0
Smith, Leisha: OK. 9580b482-17f5-4151-b80b-bf83c7deef23/152-0
Smith, Leisha: They didn't mind not hearing me. So I'm here. Can you go to that? 9580b482-17f5-4151-b80b-bf83c7deef23/153-0
Smith, Leisha: Go back back on. Where's IT when you need them? 9580b482-17f5-4151-b80b-bf83c7deef23/153-1
Smith, Leisha: Could you go to that pop out there? Is that on your laptop? 9580b482-17f5-4151-b80b-bf83c7deef23/153-2
Smith, Leisha: Can you hit it on that? 9580b482-17f5-4151-b80b-bf83c7deef23/154-0
Smith, Leisha: Oops, there was a little pop up there. 9580b482-17f5-4151-b80b-bf83c7deef23/155-0
Smith, Leisha: I don't know what's happening. 9580b482-17f5-4151-b80b-bf83c7deef23/157-0
Smith, Leisha: I think it was on teams. If you go back onto because look, 9580b482-17f5-4151-b80b-bf83c7deef23/157-1
Smith, Leisha: I hear this one the the lights logo. 9580b482-17f5-4151-b80b-bf83c7deef23/158-0
Sampath, Karuna: Can you hear me now? Yeah. OK. All right. Very good. OK. No, 9580b482-17f5-4151-b80b-bf83c7deef23/159-0
Smith, Leisha: 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
Sampath, Karuna: I didn't need to hear me. 9580b482-17f5-4151-b80b-bf83c7deef23/159-1
Smith, Leisha: because I think they could hear before. 9580b482-17f5-4151-b80b-bf83c7deef23/161-0
Smith, Leisha: This one. Can you hear me now? 9580b482-17f5-4151-b80b-bf83c7deef23/160-0
Sampath, Karuna: This one. 9580b482-17f5-4151-b80b-bf83c7deef23/162-0
Smith, Leisha: Yes. OK. OK, very good. I'll just hold on this. 9580b482-17f5-4151-b80b-bf83c7deef23/162-1
Smith, Leisha: I might minimize that and I'll go back to this. 9580b482-17f5-4151-b80b-bf83c7deef23/163-0
Smith, Leisha: All right, so clearly about 6% of all newborns have 9580b482-17f5-4151-b80b-bf83c7deef23/163-1
Smith, Leisha: a birth defect and we don't really understand what goes wrong. 9580b482-17f5-4151-b80b-bf83c7deef23/163-2
Smith, Leisha: And within the UK, about one in every 43 children that are 9580b482-17f5-4151-b80b-bf83c7deef23/163-3
Smith, Leisha: born have a birth defect. 9580b482-17f5-4151-b80b-bf83c7deef23/164-0
Smith, Leisha: And so that's about 235 per 10,000 births, of which of the 235, 9580b482-17f5-4151-b80b-bf83c7deef23/164-1
Smith, Leisha: 67 actually have heart defects. And I'll come back to this later on. 9580b482-17f5-4151-b80b-bf83c7deef23/164-2
Smith, Leisha: So why should we study a fish at all? And we've been using the fish, 9580b482-17f5-4151-b80b-bf83c7deef23/164-3
Smith, Leisha: the zebra fish as the primary experimental system. 9580b482-17f5-4151-b80b-bf83c7deef23/165-0
Smith, Leisha: to understand the basis of how the body plan gets made. 9580b482-17f5-4151-b80b-bf83c7deef23/165-1
Smith, Leisha: And here's the the beautiful zebrafish shown here below. 9580b482-17f5-4151-b80b-bf83c7deef23/165-2
Smith, Leisha: It's a small tropical fish. It actually goes in fresh waters all 9580b482-17f5-4151-b80b-bf83c7deef23/165-3
Smith, Leisha: across Asia and Southeast Asia from the foothills of the Himalayas all the way 9580b482-17f5-4151-b80b-bf83c7deef23/165-4
Smith, Leisha: through the 9580b482-17f5-4151-b80b-bf83c7deef23/167-0
Smith, Leisha: the Malayan Straits and and Southeast Asia, Singapore, Indonesia, 9580b482-17f5-4151-b80b-bf83c7deef23/167-1
Smith, Leisha: everywhere you can find this. And the reason this was picked up as a as 9580b482-17f5-4151-b80b-bf83c7deef23/167-2
Smith, Leisha: a model of organism is because of its share, surprisingly, 9580b482-17f5-4151-b80b-bf83c7deef23/167-3
Smith, Leisha: it shares 84% of the human disease genes have 9580b482-17f5-4151-b80b-bf83c7deef23/168-0
Smith, Leisha: Counterpart in Fish, the sequence, the genome sequence was done by the 9580b482-17f5-4151-b80b-bf83c7deef23/168-1
Smith, Leisha: Welcome to Sander Center and and and and they found that 84% of human disease 9580b482-17f5-4151-b80b-bf83c7deef23/168-2
Smith, Leisha: genes, even though we look so different, we actually share so many genes in common 9580b482-17f5-4151-b80b-bf83c7deef23/168-3
Smith, Leisha: and the it's a simple word. It goes extremely quickly, 9580b482-17f5-4151-b80b-bf83c7deef23/168-4
Smith, Leisha: so from the time of conception. 9580b482-17f5-4151-b80b-bf83c7deef23/169-0
Smith, Leisha: to uh when the heart beats is only 32 hours, okay. 9580b482-17f5-4151-b80b-bf83c7deef23/169-1
Smith, Leisha: So a day after the egg is fertilized by the sperm, you have a beaching heart, 9580b482-17f5-4151-b80b-bf83c7deef23/169-2
Smith, Leisha: you have a circulatory system, you have the rudiments of most of the 9580b482-17f5-4151-b80b-bf83c7deef23/169-3
Smith, Leisha: major organs. And this allows us, and and all this happens outside, 9580b482-17f5-4151-b80b-bf83c7deef23/170-0
Smith, Leisha: the water, and you can take a single cell solution 9580b482-17f5-4151-b80b-bf83c7deef23/170-1
Smith, Leisha: and keep these eggs, and you can observe how these tissues and 9580b482-17f5-4151-b80b-bf83c7deef23/170-2
Smith, Leisha: organs come together, and you can also manipulate them in many 9580b482-17f5-4151-b80b-bf83c7deef23/170-3
Smith, Leisha: ways. There have been genetic screens done 9580b482-17f5-4151-b80b-bf83c7deef23/170-4
Smith, Leisha: throughout the world, both through classical approaches, 9580b482-17f5-4151-b80b-bf83c7deef23/170-5
Smith, Leisha: and more recently through gene editing. 9580b482-17f5-4151-b80b-bf83c7deef23/171-0
Smith, Leisha: You can also do a lot of other manipulations. You can purify proteins, 9580b482-17f5-4151-b80b-bf83c7deef23/171-1
Smith, Leisha: you can purify complexes because they produce large numbers of eggs in every 9580b482-17f5-4151-b80b-bf83c7deef23/171-2
Smith, Leisha: egg lay. And of course, this is also very valuable for for doing 9580b482-17f5-4151-b80b-bf83c7deef23/171-3
Smith, Leisha: compound pharmaceutical drug screens. 9580b482-17f5-4151-b80b-bf83c7deef23/172-0
Smith, Leisha: Because you get lots of eggs that you can then test for various therapeutic avenues. 9580b482-17f5-4151-b80b-bf83c7deef23/172-1
Smith, Leisha: So I I started my early career, my my education. 9580b482-17f5-4151-b80b-bf83c7deef23/172-2
Smith, Leisha: Early education was in India. We traveled throughout the country. 9580b482-17f5-4151-b80b-bf83c7deef23/172-3
Smith, Leisha: My dad is here today. 9580b482-17f5-4151-b80b-bf83c7deef23/173-0
Smith, Leisha: So he worked for an oil company. So I went through about six or seven 9580b482-17f5-4151-b80b-bf83c7deef23/173-1
Smith, Leisha: different schools by the time I I I completed high school and I did my 9580b482-17f5-4151-b80b-bf83c7deef23/173-2
Smith, Leisha: undergraduate degree at the University of Delhi in in a women's college and then 9580b482-17f5-4151-b80b-bf83c7deef23/173-3
Smith, Leisha: did my masters at the University of Baroda. 9580b482-17f5-4151-b80b-bf83c7deef23/174-0
Smith, Leisha: So this is these are some pictures of of my college and that's my graduating 9580b482-17f5-4151-b80b-bf83c7deef23/174-1
Smith, Leisha: cohort. And this was in in a very classical 9580b482-17f5-4151-b80b-bf83c7deef23/174-2
Smith, Leisha: subject, virology, where we actually looked at specimens and 9580b482-17f5-4151-b80b-bf83c7deef23/174-3
Smith, Leisha: we drew them and and it was really utterly boring. 9580b482-17f5-4151-b80b-bf83c7deef23/175-0
Smith, Leisha: But then I I I joined the university for my master's degree in in biotechnology 9580b482-17f5-4151-b80b-bf83c7deef23/175-1
Smith, Leisha: and this is where really I I got interested in in science because we've 9580b482-17f5-4151-b80b-bf83c7deef23/175-2
Smith, Leisha: had really outstanding lectures. 9580b482-17f5-4151-b80b-bf83c7deef23/176-0
Smith, Leisha: This is Professor Bharat Chittu, who then went on to establish a genomic 9580b482-17f5-4151-b80b-bf83c7deef23/176-1
Smith, Leisha: center there. And you might recognize somebody here who 9580b482-17f5-4151-b80b-bf83c7deef23/176-2
Smith, Leisha: was working as a student in Professor Chittu's lab, 9580b482-17f5-4151-b80b-bf83c7deef23/176-3
Smith, Leisha: who's become then later on a lifelong collaborator. 9580b482-17f5-4151-b80b-bf83c7deef23/177-0
Smith, Leisha: So in addition to Professor, we also had many other very inspiring 9580b482-17f5-4151-b80b-bf83c7deef23/177-1
Smith, Leisha: lecturers, and one of these was Johannes Mandraker, 9580b482-17f5-4151-b80b-bf83c7deef23/177-2
Smith, Leisha: who had just completed his PhD with K S Krishnan at the Tapa Institute of 9580b482-17f5-4151-b80b-bf83c7deef23/177-3
Smith, Leisha: Fundamental Research. 9580b482-17f5-4151-b80b-bf83c7deef23/178-0
Smith, Leisha: He had worked on Drosophila, and about this time there were these 9580b482-17f5-4151-b80b-bf83c7deef23/178-1
Smith, Leisha: really foundational publications from the groups of Young and Baseline Forhard and 9580b482-17f5-4151-b80b-bf83c7deef23/178-2
Smith, Leisha: others where the the body plan of the fruit fly was being walked out. 9580b482-17f5-4151-b80b-bf83c7deef23/178-3
Smith, Leisha: They'd done large scale genetic screens at the. 9580b482-17f5-4151-b80b-bf83c7deef23/179-0
Smith, Leisha: in Germany, and they were just working out what these 9580b482-17f5-4151-b80b-bf83c7deef23/179-1
Smith, Leisha: pathways were. And one of these was a very fundamental 9580b482-17f5-4151-b80b-bf83c7deef23/179-2
Smith, Leisha: and really important piece of work on a protein called Bicoid, 9580b482-17f5-4151-b80b-bf83c7deef23/179-3
Smith, Leisha: which is deposited at the head, what will become the future head end of 9580b482-17f5-4151-b80b-bf83c7deef23/179-4
Smith, Leisha: the fruit fly. 9580b482-17f5-4151-b80b-bf83c7deef23/180-0
Smith, Leisha: And Wolfgang Pieber, who was the student in in Yanni Nies 9580b482-17f5-4151-b80b-bf83c7deef23/180-1
Smith, Leisha: Langvonhardt's lab, who did this work and took up, you know, 9580b482-17f5-4151-b80b-bf83c7deef23/180-2
Smith, Leisha: he basically aspirated the cytoplasm from from the egg at one end and put it into 9580b482-17f5-4151-b80b-bf83c7deef23/180-3
Smith, Leisha: the other end. And this fly now had two heads. I mean, 9580b482-17f5-4151-b80b-bf83c7deef23/180-4
Smith, Leisha: that was such a crude experiment. And I remember thinking, wow, 9580b482-17f5-4151-b80b-bf83c7deef23/180-5
Smith, Leisha: I wish I could do that. 9580b482-17f5-4151-b80b-bf83c7deef23/182-0
Smith, Leisha: And it was really nice to actually meet Wolfgang Wieder later on. 9580b482-17f5-4151-b80b-bf83c7deef23/182-1
Smith, Leisha: And here he is at the European Zebrafish meeting just a few months back in Paris 9580b482-17f5-4151-b80b-bf83c7deef23/182-2
Smith, Leisha: when I was telling him how his work had really influenced what he then went on to 9580b482-17f5-4151-b80b-bf83c7deef23/182-3
Smith, Leisha: to go on to do in in Zebrafish. 9580b482-17f5-4151-b80b-bf83c7deef23/181-0
Jawdoszak, Caroline: The. 9580b482-17f5-4151-b80b-bf83c7deef23/184-0
Smith, Leisha: So we then I went on to the United States, like many people of my generation, 9580b482-17f5-4151-b80b-bf83c7deef23/184-1
Smith, Leisha: to do a PhD in in cell and developmental biology. And I worked with Danny Stewart. 9580b482-17f5-4151-b80b-bf83c7deef23/184-2
Smith, Leisha: He was the first person to actually make a transgenic. 9580b482-17f5-4151-b80b-bf83c7deef23/185-0
Smith, Leisha: Zebrafish way back in the day when there was no fluorescent reporter, 9580b482-17f5-4151-b80b-bf83c7deef23/183-0
Jawdoszak, Caroline: What's up? 9580b482-17f5-4151-b80b-bf83c7deef23/185-1
Smith, Leisha: even had not been identified yet. He used current acetyl transferase as the 9580b482-17f5-4151-b80b-bf83c7deef23/185-2
Smith, Leisha: reporter gene, but he made the first transgenic 9580b482-17f5-4151-b80b-bf83c7deef23/185-3
Smith, Leisha: zebrafish and in his lab I worked on a new class of homeobox genes. 9580b482-17f5-4151-b80b-bf83c7deef23/187-0
Smith, Leisha: Called powdery genes and determine their expression pattern during zebrafish 9580b482-17f5-4151-b80b-bf83c7deef23/187-1
Smith, Leisha: development. And I was introduced to this beautiful 9580b482-17f5-4151-b80b-bf83c7deef23/187-2
Smith, Leisha: organism zebrafish. Following that, I went to Vanderbilt University and there 9580b482-17f5-4151-b80b-bf83c7deef23/187-3
Smith, Leisha: I worked with Chris Wright on on on frog. 9580b482-17f5-4151-b80b-bf83c7deef23/188-0
Smith, Leisha: MBA development and Chris actually was an undergrad in in the School of Life 9580b482-17f5-4151-b80b-bf83c7deef23/188-1
Smith, Leisha: Sciences at Warwick in in the 70s. So my little sweet Warwick actually had 9580b482-17f5-4151-b80b-bf83c7deef23/188-2
Smith, Leisha: had, you know, can be dated back to that time. 9580b482-17f5-4151-b80b-bf83c7deef23/190-0
Smith, Leisha: So Chris had during his early career worked on Hox genes and vertebrates. 9580b482-17f5-4151-b80b-bf83c7deef23/190-1
Smith, Leisha: He was a part of the the team of Eddie de Robertis, 9580b482-17f5-4151-b80b-bf83c7deef23/190-2
Smith, Leisha: who had identified Hox genes in frogs and and other systems. 9580b482-17f5-4151-b80b-bf83c7deef23/190-3
Smith, Leisha: And he then went on to work on one of these, 9580b482-17f5-4151-b80b-bf83c7deef23/190-4
Smith, Leisha: the pancreatic duodenal homine box gene and it's real in pancreas development. 9580b482-17f5-4151-b80b-bf83c7deef23/192-0
Smith, Leisha: But he also had a team of which I was a part of, 9580b482-17f5-4151-b80b-bf83c7deef23/192-1
Smith, Leisha: which worked on signaling growth factor signals using the fraud as a model system. 9580b482-17f5-4151-b80b-bf83c7deef23/192-2
Smith, Leisha: Because again, in those days you could get lots of eggs 9580b482-17f5-4151-b80b-bf83c7deef23/192-3
Smith, Leisha: and you could manipulate them in many different ways and you could. 9580b482-17f5-4151-b80b-bf83c7deef23/195-0
Smith, Leisha: do fundamental embiological work because the frog is actually quite large, 9580b482-17f5-4151-b80b-bf83c7deef23/195-1
Smith, Leisha: so you can manipulate them physically, you can cut out chunks of the embryo, 9580b482-17f5-4151-b80b-bf83c7deef23/195-2
Smith, Leisha: do transplantations, do explant cultures, and so on. Of course, genetically, 9580b482-17f5-4151-b80b-bf83c7deef23/195-3
Smith, Leisha: it's not as amenable as zebrafish. And so this is Chris and Mike Way, who is 9580b482-17f5-4151-b80b-bf83c7deef23/197-0
Smith, Leisha: A research assistant in his lab during my time, 9580b482-17f5-4151-b80b-bf83c7deef23/196-0
Jawdoszak, Caroline: Some students then they leave that we all having issues with it. 9580b482-17f5-4151-b80b-bf83c7deef23/197-1
Smith, Leisha: so I got a chance to to visit them again last year during the Warwick Vanderbilt 9580b482-17f5-4151-b80b-bf83c7deef23/197-2
Smith, Leisha: John Symposium. So that was really very nice to go back 9580b482-17f5-4151-b80b-bf83c7deef23/197-3
Smith, Leisha: and meet all my former colleagues. So in Chris's lab. 9580b482-17f5-4151-b80b-bf83c7deef23/198-0
Smith, Leisha: Within a couple of months of my journey in his lab, in fact, 9580b482-17f5-4151-b80b-bf83c7deef23/198-1
Smith, Leisha: and I remember this was over Thanksgiving weekend, 9580b482-17f5-4151-b80b-bf83c7deef23/198-2
Smith, Leisha: I found that one of the related group factors, 9580b482-17f5-4151-b80b-bf83c7deef23/198-3
Smith, Leisha: so this is a transforming growth factor family member. 9580b482-17f5-4151-b80b-bf83c7deef23/198-4
Smith, Leisha: I found that one of these was expressed in the problem day very early on. 9580b482-17f5-4151-b80b-bf83c7deef23/199-0
Smith, Leisha: In the left side of the embryo. So this is a frog embryo at about early 9580b482-17f5-4151-b80b-bf83c7deef23/199-1
Smith, Leisha: neural stages. We're looking at it from the back. 9580b482-17f5-4151-b80b-bf83c7deef23/199-2
Smith, Leisha: This is the midline. So you can see this is the left and this 9580b482-17f5-4151-b80b-bf83c7deef23/199-3
Smith, Leisha: is the right side and one of the neural genes was expressed in the left side and 9580b482-17f5-4151-b80b-bf83c7deef23/199-4
Smith, Leisha: 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
Smith, Leisha: develop in frog embryos. So what we did. 9580b482-17f5-4151-b80b-bf83c7deef23/200-0
Smith, Leisha: Was to take this neuro related gene and then this expressed it in what would be 9580b482-17f5-4151-b80b-bf83c7deef23/200-1
Smith, Leisha: the future right side of the embryo. And what we were able to do is to then 9580b482-17f5-4151-b80b-bf83c7deef23/200-2
Smith, Leisha: randomize the positioning of both the heart and the gut. 9580b482-17f5-4151-b80b-bf83c7deef23/200-3
Smith, Leisha: So normally in all vertebrates, the heart is positioned on the left side. 9580b482-17f5-4151-b80b-bf83c7deef23/200-4
Smith, Leisha: These embryos were. 9580b482-17f5-4151-b80b-bf83c7deef23/201-0
Smith, Leisha: where we have left-sided nodal expression. Now if you have this expressed nodal on 9580b482-17f5-4151-b80b-bf83c7deef23/201-1
Smith, Leisha: the right side, you randomize the process to a very large 9580b482-17f5-4151-b80b-bf83c7deef23/201-2
Smith, Leisha: number from those, either have right-sided hearts or have 9580b482-17f5-4151-b80b-bf83c7deef23/201-3
Smith, Leisha: hearts that don't know retreatable. And the gut, 9580b482-17f5-4151-b80b-bf83c7deef23/201-4
Smith, Leisha: which normally accords in a counterclockwise fashion in all of us, 9580b482-17f5-4151-b80b-bf83c7deef23/202-0
Smith, Leisha: They're also in the opposite orientation. And of course this is a condition that 9580b482-17f5-4151-b80b-bf83c7deef23/202-1
Smith, Leisha: happens in in human sinus syndromes and and and indeed it was really very nice to 9580b482-17f5-4151-b80b-bf83c7deef23/202-2
Smith, Leisha: see from the work of including that of this Robertson. 9580b482-17f5-4151-b80b-bf83c7deef23/203-0
Smith, Leisha: from Danny Nepson work, Michael King and Hoshi. 9580b482-17f5-4151-b80b-bf83c7deef23/205-0
Smith, Leisha: And in the chick and many groups simultaneously showed that that left 9580b482-17f5-4151-b80b-bf83c7deef23/205-1
Smith, Leisha: sided nodal expression is crucial for positioning of the organs and you see 9580b482-17f5-4151-b80b-bf83c7deef23/205-2
Smith, Leisha: that that this is also present in humans, the human nodal protein when mutated. 9580b482-17f5-4151-b80b-bf83c7deef23/208-0
Smith, Leisha: is associated with cardiovascular malformations. We also see this, 9580b482-17f5-4151-b80b-bf83c7deef23/208-1
Smith, Leisha: you know our work was published in the mid to late 90s, 9580b482-17f5-4151-b80b-bf83c7deef23/208-2
Smith, Leisha: and finding this link to humans took a bit of time, 9580b482-17f5-4151-b80b-bf83c7deef23/208-3
Smith, Leisha: but it was really very gratifying to see that the basis of cardiovascular 9580b482-17f5-4151-b80b-bf83c7deef23/206-0
Jawdoszak, Caroline: OK. 9580b482-17f5-4151-b80b-bf83c7deef23/207-0
Jawdoszak, Caroline: OK. 9580b482-17f5-4151-b80b-bf83c7deef23/208-4
Smith, Leisha: malformations, cytus defects in humans. 9580b482-17f5-4151-b80b-bf83c7deef23/209-0
Smith, Leisha: And. 9580b482-17f5-4151-b80b-bf83c7deef23/210-0
Smith, Leisha: Is often because of mutations in the protein itself, 9580b482-17f5-4151-b80b-bf83c7deef23/210-1
Smith, Leisha: and subsequent work from many groups showed that not only itself, 9580b482-17f5-4151-b80b-bf83c7deef23/210-2
Smith, Leisha: but also its core receptors, the entire signaling cascade downstream 9580b482-17f5-4151-b80b-bf83c7deef23/210-3
Smith, Leisha: of this growth factor signal. So its receptors and intracellular 9580b482-17f5-4151-b80b-bf83c7deef23/210-4
Smith, Leisha: effectors, all of these when mutated. 9580b482-17f5-4151-b80b-bf83c7deef23/212-0
Smith, Leisha: are associated with defects in in not only the the positioning of the heart, 9580b482-17f5-4151-b80b-bf83c7deef23/212-1
Smith, Leisha: they also have other defects, polysphemia, they have heterotaxy and so on. 9580b482-17f5-4151-b80b-bf83c7deef23/212-2
Smith, Leisha: So this filamental work that we did in frogs and subsequently 9580b482-17f5-4151-b80b-bf83c7deef23/211-0
Jawdoszak, Caroline: It will be large. 9580b482-17f5-4151-b80b-bf83c7deef23/213-0
Smith, Leisha: And I went on to work in Singapore. So about this time, 9580b482-17f5-4151-b80b-bf83c7deef23/213-1
Smith, Leisha: Livan was recruited to a newly formed institute in Singapore. 9580b482-17f5-4151-b80b-bf83c7deef23/213-2
Smith, Leisha: 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
Smith, Leisha: in Vanderbilt itself identified. 9580b482-17f5-4151-b80b-bf83c7deef23/215-0
Smith, Leisha: Nutritionally related genes. So then I I carried this on in in 9580b482-17f5-4151-b80b-bf83c7deef23/215-1
Smith, Leisha: Singapore in collaboration with Chris Wright and also with Lila Sovieta Kresel 9580b482-17f5-4151-b80b-bf83c7deef23/215-2
Smith, Leisha: and Marnie Halpern who was at the Carnegie Institute. 9580b482-17f5-4151-b80b-bf83c7deef23/215-3
Smith, Leisha: Lila had just joined Vanderbilt as a new faculty member. 9580b482-17f5-4151-b80b-bf83c7deef23/214-0
Jawdoszak, Caroline: It's cool. 9580b482-17f5-4151-b80b-bf83c7deef23/216-0
Smith, Leisha: So what I found was the zebrofish related genes were disrupted in a classical 9580b482-17f5-4151-b80b-bf83c7deef23/216-1
Smith, Leisha: mutant called cyclops, which had been identified in Eugenian 9580b482-17f5-4151-b80b-bf83c7deef23/216-2
Smith, Leisha: organ in the 80s in the lab of Chuck Hendel and others. 9580b482-17f5-4151-b80b-bf83c7deef23/216-3
Smith, Leisha: And this was done by classical mutagenesis. 9580b482-17f5-4151-b80b-bf83c7deef23/217-0
Smith, Leisha: gamma rays and and subsequently also by by chemical mutagenesis. 9580b482-17f5-4151-b80b-bf83c7deef23/217-1
Smith, Leisha: And the basis for this mutant was not known, 9580b482-17f5-4151-b80b-bf83c7deef23/217-2
Smith, Leisha: so as the name indicates in cyclops mutants, 9580b482-17f5-4151-b80b-bf83c7deef23/217-3
Smith, Leisha: the eyes are fused together similar to the Greek mythological character, 9580b482-17f5-4151-b80b-bf83c7deef23/217-4
Smith, Leisha: character cyclops. 9580b482-17f5-4151-b80b-bf83c7deef23/218-0
Smith, Leisha: So what I found was one of the normal genes was actually absent in the deletion 9580b482-17f5-4151-b80b-bf83c7deef23/218-1
Smith, Leisha: mutant of of fatlux and the expression pattern is altered in these mutant 9580b482-17f5-4151-b80b-bf83c7deef23/218-2
Smith, Leisha: embryos. And in collaborative work with all these 9580b482-17f5-4151-b80b-bf83c7deef23/218-3
Smith, Leisha: groups, we then showed that the the venture 9580b482-17f5-4151-b80b-bf83c7deef23/218-4
Smith, Leisha: forebrain. 9580b482-17f5-4151-b80b-bf83c7deef23/219-0
Smith, Leisha: And and the therefore the basis of cyclopia is because of defects in the 9580b482-17f5-4151-b80b-bf83c7deef23/219-1
Smith, Leisha: zebrafish nodal growth factor. So this is of course relevant to human 9580b482-17f5-4151-b80b-bf83c7deef23/219-2
Smith, Leisha: congenital birth defects. So I I need to give you an alert that 9580b482-17f5-4151-b80b-bf83c7deef23/219-3
Smith, Leisha: there's a. 9580b482-17f5-4151-b80b-bf83c7deef23/220-0
Smith, Leisha: horrible picture coming up. So you can see there's this human 9580b482-17f5-4151-b80b-bf83c7deef23/220-1
Smith, Leisha: condition called holoprosencephaly where you know these these fetuses don't make 9580b482-17f5-4151-b80b-bf83c7deef23/220-2
Smith, Leisha: it determined. They're often you know lost even before 9580b482-17f5-4151-b80b-bf83c7deef23/220-3
Smith, Leisha: that. And this is very similar to the human, 9580b482-17f5-4151-b80b-bf83c7deef23/220-4
Smith, Leisha: this human condition is very similar to the zebu fish cyclops. 9580b482-17f5-4151-b80b-bf83c7deef23/221-0
Smith, Leisha: Location. 9580b482-17f5-4151-b80b-bf83c7deef23/222-0
Smith, Leisha: You can see the eyes are close together. In other mutations, 9580b482-17f5-4151-b80b-bf83c7deef23/222-1
Smith, Leisha: there's a single eye with a single lens. And uh many of these hiliprosencephalin 9580b482-17f5-4151-b80b-bf83c7deef23/222-2
Smith, Leisha: mutations were later on found to be because of the defects in the human model 9580b482-17f5-4151-b80b-bf83c7deef23/222-3
Smith, Leisha: and pathway components of the human gene. 9580b482-17f5-4151-b80b-bf83c7deef23/223-0
Smith, Leisha: So I continue to to be very close and I was really inspired by by these, 9580b482-17f5-4151-b80b-bf83c7deef23/223-1
Smith, Leisha: these really inspiring women scientists. This is Nelia Somizakresa when she 9580b482-17f5-4151-b80b-bf83c7deef23/223-2
Smith, Leisha: visited us a few years back and Marnie Halpin, 9580b482-17f5-4151-b80b-bf83c7deef23/223-3
Smith, Leisha: who I met last year at a fish meeting in in California. 9580b482-17f5-4151-b80b-bf83c7deef23/224-0
Smith, Leisha: They're both, you know, very prominent in the field and also 9580b482-17f5-4151-b80b-bf83c7deef23/224-1
Smith, Leisha: chairs of their departments in the medical school at Washington. 9580b482-17f5-4151-b80b-bf83c7deef23/224-2
Smith, Leisha: Mila just stepped down, and Lani is the chair of the Geser School 9580b482-17f5-4151-b80b-bf83c7deef23/224-3
Smith, Leisha: of Medicine at Dartmouth Village. 9580b482-17f5-4151-b80b-bf83c7deef23/225-0
Smith, Leisha: So I've been very fortunate to have worked with really inspiring 9580b482-17f5-4151-b80b-bf83c7deef23/225-1
Smith, Leisha: collaborators and and inspiring women scientists throughout my career. 9580b482-17f5-4151-b80b-bf83c7deef23/225-2
Smith, Leisha: So following this work, I I became a fellow at the Institute of 9580b482-17f5-4151-b80b-bf83c7deef23/225-3
Smith, Leisha: Molecular Agrobiology in Singapore. 9580b482-17f5-4151-b80b-bf83c7deef23/226-0
Smith, Leisha: And like many others in the field, I tried to work out the reduction 9580b482-17f5-4151-b80b-bf83c7deef23/226-1
Smith, Leisha: components of the identified model, which is a group factor signal. 9580b482-17f5-4151-b80b-bf83c7deef23/226-2
Smith, Leisha: We wanted to see what it it how it transduces its signal inside the cell. 9580b482-17f5-4151-b80b-bf83c7deef23/227-0
Smith, Leisha: And I spent about a year doing this and I was scooped left, 9580b482-17f5-4151-b80b-bf83c7deef23/227-1
Smith, Leisha: right and centre by very large teams across the world. 9580b482-17f5-4151-b80b-bf83c7deef23/227-2
Smith, Leisha: This was a very hot area, transforming group factor beta signalling 9580b482-17f5-4151-b80b-bf83c7deef23/227-3
Smith, Leisha: was being studied by many groups both in the UK and the United States. 9580b482-17f5-4151-b80b-bf83c7deef23/228-0
Smith, Leisha: And I wasn't making any progress. Any progress I would make would be would 9580b482-17f5-4151-b80b-bf83c7deef23/228-1
Smith, Leisha: show up in the next issue of of Nature or Cell. And so at this point, 9580b482-17f5-4151-b80b-bf83c7deef23/228-2
Smith, Leisha: the director of the Institute of Pond Biologist by the name Sundar put me out 9580b482-17f5-4151-b80b-bf83c7deef23/228-3
Smith, Leisha: and said, why are you doing what everybody else is 9580b482-17f5-4151-b80b-bf83c7deef23/228-4
Smith, Leisha: doing? This is really you shouldn't be doing 9580b482-17f5-4151-b80b-bf83c7deef23/228-5
Smith, Leisha: what everybody is doing. 9580b482-17f5-4151-b80b-bf83c7deef23/229-0
Smith, Leisha: You should really be doing something that's unique and distinctive and gives 9580b482-17f5-4151-b80b-bf83c7deef23/229-1
Smith, Leisha: you room to grow. And I think this is really very good 9580b482-17f5-4151-b80b-bf83c7deef23/229-2
Smith, Leisha: advice. And I was able to actually benefit from 9580b482-17f5-4151-b80b-bf83c7deef23/229-3
Smith, Leisha: this because I also found about that time that one of the little related RNAs 9580b482-17f5-4151-b80b-bf83c7deef23/230-0
Smith, Leisha: is actually expressed not only in the embryo, 9580b482-17f5-4151-b80b-bf83c7deef23/230-1
Smith, Leisha: 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
Smith, Leisha: And so RNA is being localized in the egg and early embryo in Drosophila and in C. 9580b482-17f5-4151-b80b-bf83c7deef23/230-3
Smith, Leisha: elegans. 9580b482-17f5-4151-b80b-bf83c7deef23/232-0
Smith, Leisha: had been found to be very important for positioning various cells and tissues in 9580b482-17f5-4151-b80b-bf83c7deef23/232-1
Smith, Leisha: neutral embryogenesis. So, fortunately, the institute advisory board comprised of 9580b482-17f5-4151-b80b-bf83c7deef23/232-2
Smith, Leisha: very eminent scientists, Daniel Lirard, who was the director of the Curie 9580b482-17f5-4151-b80b-bf83c7deef23/232-3
Smith, Leisha: Institute at the time, and 9580b482-17f5-4151-b80b-bf83c7deef23/233-0
Smith, Leisha: who was the director general of EMBL Hyderabad. And incidentally, 9580b482-17f5-4151-b80b-bf83c7deef23/233-1
Smith, Leisha: Fertlis is also the founding president. He established the European Research 9580b482-17f5-4151-b80b-bf83c7deef23/233-2
Smith, Leisha: Council, which many people throughout Europe 9580b482-17f5-4151-b80b-bf83c7deef23/233-3
Smith, Leisha: benefit from to this day. So these people could be in touch with 9580b482-17f5-4151-b80b-bf83c7deef23/233-4
Smith, Leisha: Ana Frithi. 9580b482-17f5-4151-b80b-bf83c7deef23/234-0
Smith, Leisha: who was at EMBL and arranged for me to visit her lab. 9580b482-17f5-4151-b80b-bf83c7deef23/234-1
Smith, Leisha: So Anne's lab had been working on localized RNAs in the fly egg. 9580b482-17f5-4151-b80b-bf83c7deef23/234-2
Smith, Leisha: She had been working on oscar mRNA, which is localized to the posterior core 9580b482-17f5-4151-b80b-bf83c7deef23/234-3
Smith, Leisha: of the drosophila egg. And it's crucial for finding the germline, 9580b482-17f5-4151-b80b-bf83c7deef23/234-4
Smith, Leisha: the reproductive structures of the fly. 9580b482-17f5-4151-b80b-bf83c7deef23/235-0
Smith, Leisha: So I was sent off to Ann's lab, and Ann is really a fantastic person and 9580b482-17f5-4151-b80b-bf83c7deef23/235-1
Smith, Leisha: a really another inspiring scientist. She's in fact retiring. 9580b482-17f5-4151-b80b-bf83c7deef23/235-2
Smith, Leisha: Her retiring symposium is tomorrow, which I am unfortunately going to miss. 9580b482-17f5-4151-b80b-bf83c7deef23/235-3
Smith, Leisha: I had to send her my regrets. 9580b482-17f5-4151-b80b-bf83c7deef23/236-0
Smith, Leisha: 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
Smith, Leisha: localized to one end, how do they generate, in this case, 9580b482-17f5-4151-b80b-bf83c7deef23/236-2
Smith, Leisha: the germline of the fruit fly. So Eden was working on on a zebrafish. 9580b482-17f5-4151-b80b-bf83c7deef23/237-0
Smith, Leisha: Army. I was sent there for about for a couple 9580b482-17f5-4151-b80b-bf83c7deef23/237-1
Smith, Leisha: of months and it was really a very nice atmosphere because I could learn, 9580b482-17f5-4151-b80b-bf83c7deef23/237-2
Smith, Leisha: I could see what techniques they were using and then adapt them and to 9580b482-17f5-4151-b80b-bf83c7deef23/237-3
Smith, Leisha: zebrafish. And so I came back and then started my 9580b482-17f5-4151-b80b-bf83c7deef23/237-4
Smith, Leisha: own program looking at localization of these armies. 9580b482-17f5-4151-b80b-bf83c7deef23/238-0
Smith, Leisha: In zebrafish eggs and about this time also our son was born shown here and the 9580b482-17f5-4151-b80b-bf83c7deef23/238-1
Smith, Leisha: institute did not have a child care facility. 9580b482-17f5-4151-b80b-bf83c7deef23/238-2
Smith, Leisha: So I was very fortunate to lean on our parents. 9580b482-17f5-4151-b80b-bf83c7deef23/238-3
Smith, Leisha: So this is Mohan's parents and here are my parents, my dad. 9580b482-17f5-4151-b80b-bf83c7deef23/239-0
Smith, Leisha: here today for childcare. And because the institute didn't have a 9580b482-17f5-4151-b80b-bf83c7deef23/239-1
Smith, Leisha: daycare facility, I then tried to to set up one, 9580b482-17f5-4151-b80b-bf83c7deef23/239-2
Smith, Leisha: but it just took, you know, finding the money, the approvals, 9580b482-17f5-4151-b80b-bf83c7deef23/239-3
Smith, Leisha: everything took so long. My son was five years old by the time 9580b482-17f5-4151-b80b-bf83c7deef23/239-4
Smith, Leisha: that that I was actually able to do this. Yeah, even in Singapore, 9580b482-17f5-4151-b80b-bf83c7deef23/239-5
Smith, Leisha: these things take time. 9580b482-17f5-4151-b80b-bf83c7deef23/240-0
Smith, Leisha: But I think I I'd like to think that, you know, whatever I do in science, 9580b482-17f5-4151-b80b-bf83c7deef23/240-1
Smith, Leisha: you know, this is perhaps, you know, more important because it enabled a lot 9580b482-17f5-4151-b80b-bf83c7deef23/240-2
Smith, Leisha: of young people to actually be able to continue working in in those early stages 9580b482-17f5-4151-b80b-bf83c7deef23/240-3
Smith, Leisha: of their career when they need so much support. 9580b482-17f5-4151-b80b-bf83c7deef23/241-0
Smith, Leisha: OK. And so then in my new lab, I started to look at little limb RNAs and 9580b482-17f5-4151-b80b-bf83c7deef23/241-1
Smith, Leisha: how they are distributed in in early eggs and embryos. 9580b482-17f5-4151-b80b-bf83c7deef23/241-2
Smith, Leisha: So here's a nodal RNA that we found distributed in two daughter cells at the 9580b482-17f5-4151-b80b-bf83c7deef23/241-3
Smith, Leisha: four cell stage. And I have to say I had some really 9580b482-17f5-4151-b80b-bf83c7deef23/241-4
Smith, Leisha: fantastic students and postdocs. 9580b482-17f5-4151-b80b-bf83c7deef23/242-0
Smith, Leisha: who then really drove this direction. And Anike, 9580b482-17f5-4151-b80b-bf83c7deef23/242-1
Smith, Leisha: who's who was the first student to actually join the lab, 9580b482-17f5-4151-b80b-bf83c7deef23/242-2
Smith, Leisha: the first PhD student, he's currently working, 9580b482-17f5-4151-b80b-bf83c7deef23/242-3
Smith, Leisha: he's leading the entire East Coast of the United States for Oxford Manipore. 9580b482-17f5-4151-b80b-bf83c7deef23/244-0
Smith, Leisha: So he's really gone on to be very successful. 9580b482-17f5-4151-b80b-bf83c7deef23/244-1
Smith, Leisha: So he generated synthetic little mRNA. We saw some tags on it. 9580b482-17f5-4151-b80b-bf83c7deef23/244-2
Smith, Leisha: And because zebrafish eggs are very amenable to experimental manipulation, 9580b482-17f5-4151-b80b-bf83c7deef23/244-3
Smith, Leisha: he injected it and using the transparency of the zebrafish, 9580b482-17f5-4151-b80b-bf83c7deef23/243-0
Jawdoszak, Caroline: No. 9580b482-17f5-4151-b80b-bf83c7deef23/244-4
Smith, Leisha: we could then do live imaging. 9580b482-17f5-4151-b80b-bf83c7deef23/246-0
Smith, Leisha: and see that the synthetic RNA also went to two daughter cells at the four cell 9580b482-17f5-4151-b80b-bf83c7deef23/245-0
Jawdoszak, Caroline: Yeah. 9580b482-17f5-4151-b80b-bf83c7deef23/246-1
Smith, Leisha: stage. So what are these these cells that 9580b482-17f5-4151-b80b-bf83c7deef23/246-2
Smith, Leisha: inherit this RNA? So to test that, what we did was to actually inject that 9580b482-17f5-4151-b80b-bf83c7deef23/246-3
Smith, Leisha: fluorescence reporter and then actually dissect out normally using an eyelash 9580b482-17f5-4151-b80b-bf83c7deef23/246-4
Smith, Leisha: tool, removing the cells 9580b482-17f5-4151-b80b-bf83c7deef23/247-0
Smith, Leisha: Contain the fluorescent RNA. And normally this is what a little fish 9580b482-17f5-4151-b80b-bf83c7deef23/247-1
Smith, Leisha: egg looks 24 hours after conception. There's the eye, there's the brain. 9580b482-17f5-4151-b80b-bf83c7deef23/247-2
Smith, Leisha: The heart would be beating here and there's the spinal cord. OK, 9580b482-17f5-4151-b80b-bf83c7deef23/247-3
Smith, Leisha: but then in these embolos where we have removed those two cells, 9580b482-17f5-4151-b80b-bf83c7deef23/247-4
Smith, Leisha: we actually don't have a head. OK, these embolos. 9580b482-17f5-4151-b80b-bf83c7deef23/248-0
Smith, Leisha: Black anterior and dorsal structures. So the cells that contain the RNA are 9580b482-17f5-4151-b80b-bf83c7deef23/248-1
Smith, Leisha: crucial for the feet of these anterior dorsal structures, the head. 9580b482-17f5-4151-b80b-bf83c7deef23/248-2
Smith, Leisha: And this is shown with marker genes. So here is Sonic hedgehog expression in 9580b482-17f5-4151-b80b-bf83c7deef23/248-3
Smith, Leisha: the fore, mid, hindbrain and spinal cord. 9580b482-17f5-4151-b80b-bf83c7deef23/249-0
Smith, Leisha: you can see in these quintremoved cells, there's hardly any or no expression of 9580b482-17f5-4151-b80b-bf83c7deef23/249-1
Smith, Leisha: Sonic hedgehog. So these RNAs have to be inherited by 9580b482-17f5-4151-b80b-bf83c7deef23/249-2
Smith, Leisha: these cells to form these important head and anterior structures. 9580b482-17f5-4151-b80b-bf83c7deef23/249-3
Smith, Leisha: So this was work we published 9580b482-17f5-4151-b80b-bf83c7deef23/250-0
Smith, Leisha: in nature and and Anika and Patrick were really crucial for this work and also 9580b482-17f5-4151-b80b-bf83c7deef23/250-1
Smith, Leisha: Albert Chung who was a technician in the lab. 9580b482-17f5-4151-b80b-bf83c7deef23/250-2
Smith, Leisha: This was again done collaboratively with Shingo Maigawa in Eric Rivenberg's lab at 9580b482-17f5-4151-b80b-bf83c7deef23/250-3
Smith, Leisha: Penn. So I was very fortunate to have very good 9580b482-17f5-4151-b80b-bf83c7deef23/250-4
Smith, Leisha: collaborators who actually helped us 9580b482-17f5-4151-b80b-bf83c7deef23/251-0
Smith, Leisha: out this work. Patrick came from a lab that had been 9580b482-17f5-4151-b80b-bf83c7deef23/251-1
Smith, Leisha: looking at you know evolutionary conservation of of regulatory elements in 9580b482-17f5-4151-b80b-bf83c7deef23/251-2
Smith, Leisha: the mouse and and food and other species. So he basically went to a fish market in 9580b482-17f5-4151-b80b-bf83c7deef23/251-3
Smith, Leisha: Singapore and the next thing I knew 9580b482-17f5-4151-b80b-bf83c7deef23/253-0
Smith, Leisha: The lab was full of like little pots of like all kinds of fish swimming about and 9580b482-17f5-4151-b80b-bf83c7deef23/253-1
Smith, Leisha: this is really something that he could do very easily there. 9580b482-17f5-4151-b80b-bf83c7deef23/253-2
Smith, Leisha: He could just walk through a market, buy a bunch of different species, 9580b482-17f5-4151-b80b-bf83c7deef23/253-3
Smith, Leisha: 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
Smith, Leisha: isolate DNA and RNA from these and then looked at the little sequences in all 9580b482-17f5-4151-b80b-bf83c7deef23/253-5
Smith, Leisha: these different fish. 9580b482-17f5-4151-b80b-bf83c7deef23/254-0
Smith, Leisha: And by by aligning them with zebrafish, he was able to identify signatures that 9580b482-17f5-4151-b80b-bf83c7deef23/254-1
Smith, Leisha: seem to be present in in all these fish species. OK, 9580b482-17f5-4151-b80b-bf83c7deef23/254-2
Smith, Leisha: so he then also compared this. Sorry, I went a bit fast. 9580b482-17f5-4151-b80b-bf83c7deef23/255-0
Smith, Leisha: He also found that some of these were found also in human dogs and chill 9580b482-17f5-4151-b80b-bf83c7deef23/255-1
Smith, Leisha: sequences that other people had had previously published. 9580b482-17f5-4151-b80b-bf83c7deef23/255-2
Smith, Leisha: So he was able to find these signatures and. 9580b482-17f5-4151-b80b-bf83c7deef23/256-0
Smith, Leisha: Usually this region which have these signatures sequences. 9580b482-17f5-4151-b80b-bf83c7deef23/256-1
Smith, Leisha: So these are sort of like pin codes in your mail at mailing address. OK, 9580b482-17f5-4151-b80b-bf83c7deef23/256-2
Smith, Leisha: so if we say CB47AL, we know our mails shouldn't come here, 9580b482-17f5-4151-b80b-bf83c7deef23/256-3
Smith, Leisha: but then if you scramble this code and you need to see B7AL4. 9580b482-17f5-4151-b80b-bf83c7deef23/257-0
Smith, Leisha: I don't know where in Coventry it's going to end up. OK, 9580b482-17f5-4151-b80b-bf83c7deef23/257-1
Smith, Leisha: or you could delete out regions in between. You could be on the C&L, 9580b482-17f5-4151-b80b-bf83c7deef23/257-2
Smith, Leisha: you know, the post office doesn't know what to do 9580b482-17f5-4151-b80b-bf83c7deef23/257-3
Smith, Leisha: with your meal. And essentially that's what happens with 9580b482-17f5-4151-b80b-bf83c7deef23/257-4
Smith, Leisha: these sequences as well. These are recognized by the similar 9580b482-17f5-4151-b80b-bf83c7deef23/257-5
Smith, Leisha: machinery, sorted and then putting them into the 9580b482-17f5-4151-b80b-bf83c7deef23/257-6
Smith, Leisha: right. 9580b482-17f5-4151-b80b-bf83c7deef23/258-0
Smith, Leisha: cells at the right time. And Patrick essentially identified the 9580b482-17f5-4151-b80b-bf83c7deef23/258-1
Smith, Leisha: key protein that recognizes these elements by purifying the complex that 9580b482-17f5-4151-b80b-bf83c7deef23/258-2
Smith, Leisha: binds to this RNA. And through this, we were able to identify the key protein 9580b482-17f5-4151-b80b-bf83c7deef23/258-3
Smith, Leisha: VIBOX1, which we work on in my lab to this day. 9580b482-17f5-4151-b80b-bf83c7deef23/259-0
Smith, Leisha: in BiBox 1 actually result in the RNA instead of going to two daughter cells, 9580b482-17f5-4151-b80b-bf83c7deef23/259-1
Smith, Leisha: 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
Smith, Leisha: cells, right time. We also made other mutations to remove 9580b482-17f5-4151-b80b-bf83c7deef23/259-3
Smith, Leisha: the the pin code itself. And we also found the sorting machinery 9580b482-17f5-4151-b80b-bf83c7deef23/260-0
Smith, Leisha: the main key components, the microtubule cytoskeleton, 9580b482-17f5-4151-b80b-bf83c7deef23/260-1
Smith, Leisha: which transmits the RNA to the hood order cell. 9580b482-17f5-4151-b80b-bf83c7deef23/260-2
Smith, Leisha: So I'm I'm actually summarizing probably many, 9580b482-17f5-4151-b80b-bf83c7deef23/260-3
Smith, Leisha: many years of work by many talented students in the lab. So here's Shinin, 9580b482-17f5-4151-b80b-bf83c7deef23/260-4
Smith, Leisha: who made the mutations in the little three prime UTR, and that's the 9580b482-17f5-4151-b80b-bf83c7deef23/261-0
Smith, Leisha: Cake she got when her paper was published, showing the two daughter cells there. 9580b482-17f5-4151-b80b-bf83c7deef23/261-1
Smith, Leisha: Yeah, my lab's always been partial to desserts 9580b482-17f5-4151-b80b-bf83c7deef23/261-2
Smith, Leisha: and cake in particular. So this is a very long standing tradition 9580b482-17f5-4151-b80b-bf83c7deef23/261-3
Smith, Leisha: and Pooja did the work on Y box 1. So following Patrick's work, 9580b482-17f5-4151-b80b-bf83c7deef23/261-4
Smith, Leisha: she she studied the the genome editing mutants. 9580b482-17f5-4151-b80b-bf83c7deef23/262-0
Smith, Leisha: umm in AMI box 1 and showed that the RNA is mislocalized and then Tran identified 9580b482-17f5-4151-b80b-bf83c7deef23/262-1
Smith, Leisha: the the microtubule tracks through which the RNA is actually transported and sent 9580b482-17f5-4151-b80b-bf83c7deef23/262-2
Smith, Leisha: to the correct location. So essentially the the the the poster 9580b482-17f5-4151-b80b-bf83c7deef23/262-3
Smith, Leisha: machinery is that if you will. 9580b482-17f5-4151-b80b-bf83c7deef23/263-0
Smith, Leisha: And here they are as graduates. And this is Shijie, 9580b482-17f5-4151-b80b-bf83c7deef23/263-1
Smith, Leisha: who is actually working on a different JiJie beta signal, the signaling, 9580b482-17f5-4151-b80b-bf83c7deef23/263-2
Smith, Leisha: and how it's regulated in the early embryo. 9580b482-17f5-4151-b80b-bf83c7deef23/263-3
Smith, Leisha: So we had identified a crucial pin code, which allows the 9580b482-17f5-4151-b80b-bf83c7deef23/264-0
Smith, Leisha: Signal RNA to be turned on to the right place, right time. 9580b482-17f5-4151-b80b-bf83c7deef23/264-1
Smith, Leisha: It also sends it to the correct location. So it's these RNAs are made in the 9580b482-17f5-4151-b80b-bf83c7deef23/264-2
Smith, Leisha: nucleus, but they need to be distributed in these 9580b482-17f5-4151-b80b-bf83c7deef23/264-3
Smith, Leisha: two daughter cells because if you remove these cells, you don't have a head, OK. 9580b482-17f5-4151-b80b-bf83c7deef23/265-0
Smith, Leisha: And we also need to keep it in a certain seat. You need to, 9580b482-17f5-4151-b80b-bf83c7deef23/265-1
Smith, Leisha: 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
Smith, Leisha: right time. And that's what that that complex that 9580b482-17f5-4151-b80b-bf83c7deef23/265-3
Smith, Leisha: Patrick had purified does. You turn it on at the right place, 9580b482-17f5-4151-b80b-bf83c7deef23/265-4
Smith, Leisha: right time and then allow the signal to to be distributed. 9580b482-17f5-4151-b80b-bf83c7deef23/266-0
Smith, Leisha: So if you turn it on too soon, you actually also create problems with 9580b482-17f5-4151-b80b-bf83c7deef23/266-1
Smith, Leisha: the embryo. They start to differentiate in ways that 9580b482-17f5-4151-b80b-bf83c7deef23/266-2
Smith, Leisha: they would normally not do, and I'll come back to this later. 9580b482-17f5-4151-b80b-bf83c7deef23/266-3
Smith, Leisha: If you don't have any signal, that's also a problem. 9580b482-17f5-4151-b80b-bf83c7deef23/266-4
Smith, Leisha: You get cycloplas and you miss chunks of the spinal cord, 9580b482-17f5-4151-b80b-bf83c7deef23/266-5
Smith, Leisha: and that also leads to illegality. 9580b482-17f5-4151-b80b-bf83c7deef23/268-0
Smith, Leisha: So I think you need to have these turn on at the right place, 9580b482-17f5-4151-b80b-bf83c7deef23/268-1
Smith, Leisha: right time and the right level. So what controls this? 9580b482-17f5-4151-b80b-bf83c7deef23/268-2
Smith, Leisha: So this is something that we will then spend some time trying to work out. 9580b482-17f5-4151-b80b-bf83c7deef23/268-3
Smith, Leisha: So these are all group factor signals. They're made by one cell and then somehow 9580b482-17f5-4151-b80b-bf83c7deef23/268-4
Smith, Leisha: sent out and then another cell should then receive this and then. 9580b482-17f5-4151-b80b-bf83c7deef23/269-0
Smith, Leisha: the song. So how how does this happen? And of course, we got from the, 9580b482-17f5-4151-b80b-bf83c7deef23/269-1
Smith, Leisha: we know from the really similar work that that the the concentration, 9580b482-17f5-4151-b80b-bf83c7deef23/269-2
Smith, Leisha: the amount of of a morphogen, of a growth factor signal is very crucial. 9580b482-17f5-4151-b80b-bf83c7deef23/269-3
Smith, Leisha: For cells that are very close to the source, we receive very high amounts 9580b482-17f5-4151-b80b-bf83c7deef23/271-0
Smith, Leisha: And as we go further and further away from the source, 9580b482-17f5-4151-b80b-bf83c7deef23/271-1
Smith, Leisha: we'll see less and less of it. And that actually has an impact on how 9580b482-17f5-4151-b80b-bf83c7deef23/271-2
Smith, Leisha: the cells respond and how what they turn into. So how does this happen? 9580b482-17f5-4151-b80b-bf83c7deef23/271-3
Smith, Leisha: So we know that the levels are important because if you have neuronal signal, 9580b482-17f5-4151-b80b-bf83c7deef23/271-4
Smith, Leisha: you basically get cyclopent. 9580b482-17f5-4151-b80b-bf83c7deef23/272-0
Smith, Leisha: Here. 9580b482-17f5-4151-b80b-bf83c7deef23/273-0
Smith, Leisha: We have a little bit. You get eyes that are close together, 9580b482-17f5-4151-b80b-bf83c7deef23/273-1
Smith, Leisha: but not completely fused. But they're also not normal because 9580b482-17f5-4151-b80b-bf83c7deef23/273-2
Smith, Leisha: they're lacking parts of the ventral brain, and so on and so forth. 9580b482-17f5-4151-b80b-bf83c7deef23/273-3
Smith, Leisha: And similarly, if we put too much of nodal, 9580b482-17f5-4151-b80b-bf83c7deef23/273-4
Smith, Leisha: that also leads to problems. So you're basically instead of having 9580b482-17f5-4151-b80b-bf83c7deef23/273-5
Smith, Leisha: this nice French flag, you actually have too much. 9580b482-17f5-4151-b80b-bf83c7deef23/274-0
Smith, Leisha: or too little of of one or other color, which is devastating for the embryo 9580b482-17f5-4151-b80b-bf83c7deef23/274-1
Smith, Leisha: itself. So when does the signal get turned on? 9580b482-17f5-4151-b80b-bf83c7deef23/274-2
Smith, Leisha: This was figured out by Pinjin, a student in the lab. 9580b482-17f5-4151-b80b-bf83c7deef23/274-3
Smith, Leisha: And I was really very pleased to see her then go on to to establish her own 9580b482-17f5-4151-b80b-bf83c7deef23/274-4
Smith, Leisha: research group in China. 9580b482-17f5-4151-b80b-bf83c7deef23/275-0
Smith, Leisha: And there she is with her students, where she's continuing to work on on 9580b482-17f5-4151-b80b-bf83c7deef23/275-1
Smith, Leisha: fundamentally fundamental problems in in development, 9580b482-17f5-4151-b80b-bf83c7deef23/275-2
Smith, Leisha: not only in in the zebrafish but also in the mouse. 9580b482-17f5-4151-b80b-bf83c7deef23/275-3
Smith, Leisha: And here's another trainee from my lab. This is Ruan Hua and this is actually. 9580b482-17f5-4151-b80b-bf83c7deef23/276-0
Smith, Leisha: Wan Zhang was in Lun's lab, so they've all gone back to lead their 9580b482-17f5-4151-b80b-bf83c7deef23/276-1
Smith, Leisha: own teams in China as group leaders. So Wan was part of a large scale 9580b482-17f5-4151-b80b-bf83c7deef23/276-2
Smith, Leisha: midgenesis school. So in addition to studying these pathways, 9580b482-17f5-4151-b80b-bf83c7deef23/276-3
Smith, Leisha: we also developed a lot of tools along the way which were not present, 9580b482-17f5-4151-b80b-bf83c7deef23/276-4
Smith, Leisha: so using the. 9580b482-17f5-4151-b80b-bf83c7deef23/277-0
Smith, Leisha: ACDS plant transfers on system. We generated a bank of meetings and was 9580b482-17f5-4151-b80b-bf83c7deef23/277-1
Smith, Leisha: part of the team that that worked on this very large effort by many, many groups. 9580b482-17f5-4151-b80b-bf83c7deef23/277-2
Smith, Leisha: And I again had a chance to collaborate with her in in looking at another 9580b482-17f5-4151-b80b-bf83c7deef23/277-3
Smith, Leisha: civilian pathway. 9580b482-17f5-4151-b80b-bf83c7deef23/278-0
Smith, Leisha: Has signaling and it's real in in fertilization in the egg some years later. 9580b482-17f5-4151-b80b-bf83c7deef23/278-1
Smith, Leisha: So we we also looked at how the the nodal growth factor itself is is distributed 9580b482-17f5-4151-b80b-bf83c7deef23/278-2
Smith, Leisha: and this was work done by by a student on in collaboration with. 9580b482-17f5-4151-b80b-bf83c7deef23/279-0
Smith, Leisha: um who's a biophysicist, and and he helped us to determine not 9580b482-17f5-4151-b80b-bf83c7deef23/279-1
Smith, Leisha: only the the diffusivity of this growth factor in vivo in living embryos, 9580b482-17f5-4151-b80b-bf83c7deef23/279-2
Smith, Leisha: we also looked at the binding affinity to its receptors in the living embryo, 9580b482-17f5-4151-b80b-bf83c7deef23/279-3
Smith, Leisha: and we were able to to model this computationally. 9580b482-17f5-4151-b80b-bf83c7deef23/280-0
Smith, Leisha: as well. So this was work that we did together 9580b482-17f5-4151-b80b-bf83c7deef23/280-1
Smith, Leisha: with Thorsten and we continue to collaborate with him. 9580b482-17f5-4151-b80b-bf83c7deef23/280-2
Smith, Leisha: We have a paper that we hope will come out very soon in communications, 9580b482-17f5-4151-b80b-bf83c7deef23/280-3
Smith, Leisha: following up on this work we did on the gradient. So this work was 9580b482-17f5-4151-b80b-bf83c7deef23/281-0
Smith, Leisha: It's also complemented by by other technological advances that we were 9580b482-17f5-4151-b80b-bf83c7deef23/281-1
Smith, Leisha: contributing towards. So we generated genome editing deletions 9580b482-17f5-4151-b80b-bf83c7deef23/281-2
Smith, Leisha: in targeted regions of the genome, and this was published in Genome Biology 9580b482-17f5-4151-b80b-bf83c7deef23/281-3
Smith, Leisha: and you can see one in a shim. 9580b482-17f5-4151-b80b-bf83c7deef23/282-0
Smith, Leisha: Celebrating this with this publication with their cake. 9580b482-17f5-4151-b80b-bf83c7deef23/282-1
Smith, Leisha: So around this time the lab was getting ready to room. 9580b482-17f5-4151-b80b-bf83c7deef23/282-2
Smith, Leisha: 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
Smith, Leisha: at that time and some of you might recognize. 9580b482-17f5-4151-b80b-bf83c7deef23/283-0
Smith, Leisha: Mr. 9580b482-17f5-4151-b80b-bf83c7deef23/284-0
Smith, Leisha: I had a woman here, Pavly Vrlichak, who then came to to Warwick to 1st set up 9580b482-17f5-4151-b80b-bf83c7deef23/284-1
Smith, Leisha: the lab. So I was very fortunate that some of the 9580b482-17f5-4151-b80b-bf83c7deef23/284-2
Smith, Leisha: team that was in Singapore could come here and help me set up the new lab in 9580b482-17f5-4151-b80b-bf83c7deef23/284-3
Smith, Leisha: this new place. So Pavly was part of the the large scale 9580b482-17f5-4151-b80b-bf83c7deef23/284-4
Smith, Leisha: lab. 9580b482-17f5-4151-b80b-bf83c7deef23/285-0
Smith, Leisha: gene screen that we did in the ACDS transposon. So, 9580b482-17f5-4151-b80b-bf83c7deef23/285-1
Smith, Leisha: Helen was the lead for the functional analysis. 9580b482-17f5-4151-b80b-bf83c7deef23/285-2
Smith, Leisha: Harvey essentially mapped where these sensations were. 9580b482-17f5-4151-b80b-bf83c7deef23/285-3
Smith, Leisha: And we did this in collaboration with Sean Burgess, 9580b482-17f5-4151-b80b-bf83c7deef23/285-4
Smith, Leisha: who's the head of functional genomics 9580b482-17f5-4151-b80b-bf83c7deef23/286-0
Smith, Leisha: At NIH, not a very easy job these days, but he helped us with this work. 9580b482-17f5-4151-b80b-bf83c7deef23/286-1
Smith, Leisha: So Parde was the first person who moved across. 9580b482-17f5-4151-b80b-bf83c7deef23/286-2
Smith, Leisha: So while we were wiping the lab down in Singapore and things were being shipped, 9580b482-17f5-4151-b80b-bf83c7deef23/286-3
Smith, Leisha: he just sat and did this computation lab. 9580b482-17f5-4151-b80b-bf83c7deef23/287-0
Smith, Leisha: Analysis was really very, very helpful and this was published in G3 9580b482-17f5-4151-b80b-bf83c7deef23/287-1
Smith, Leisha: as back-to-back papers and we took this whole collection of hundreds of mutant 9580b482-17f5-4151-b80b-bf83c7deef23/287-2
Smith, Leisha: lines and deposited them with the European Zebra Fish Resource Center and 9580b482-17f5-4151-b80b-bf83c7deef23/287-3
Smith, Leisha: I'm very grateful to the White Impact Fund which allowed us. 9580b482-17f5-4151-b80b-bf83c7deef23/288-0
Smith, Leisha: To to actually deposit this collection as a resource that can be used freely by the 9580b482-17f5-4151-b80b-bf83c7deef23/288-1
Smith, Leisha: worldwide community. So Sadesh Kumar really helped us get 9580b482-17f5-4151-b80b-bf83c7deef23/288-2
Smith, Leisha: these funds. So we have to build a new fish facility 9580b482-17f5-4151-b80b-bf83c7deef23/288-3
Smith, Leisha: here and this was enabled by a Wellcome Trust International Award to Mohan. 9580b482-17f5-4151-b80b-bf83c7deef23/289-0
Smith, Leisha: Which also allowed us to to to to match with funds from Warwick to build this 9580b482-17f5-4151-b80b-bf83c7deef23/289-1
Smith, Leisha: museum for facility. This is the early days of the facility. 9580b482-17f5-4151-b80b-bf83c7deef23/289-2
Smith, Leisha: You might recognize some of the people from that time. 9580b482-17f5-4151-b80b-bf83c7deef23/289-3
Smith, Leisha: Ian and Sarah are still there. So this was and we celebrated this of 9580b482-17f5-4151-b80b-bf83c7deef23/289-4
Smith, Leisha: course with the symposium and this key was actually built. 9580b482-17f5-4151-b80b-bf83c7deef23/290-0
Smith, Leisha: by by Lavinia Sivasanmukkal. You can see the lovely fish here. 9580b482-17f5-4151-b80b-bf83c7deef23/290-1
Smith, Leisha: They were all species, but it was still delicious. So at Warwick, 9580b482-17f5-4151-b80b-bf83c7deef23/290-2
Smith, Leisha: what did we do? So building on our findings in the 9580b482-17f5-4151-b80b-bf83c7deef23/290-3
Smith, Leisha: zebrafish models, by we I mean Jan Gorotkin at the Center 9580b482-17f5-4151-b80b-bf83c7deef23/290-4
Smith, Leisha: for Non-coding RNAs in Copenhagen. 9580b482-17f5-4151-b80b-bf83c7deef23/291-0
Smith, Leisha: Looked at all the mammalian sequences and tried to see where these pin codes that 9580b482-17f5-4151-b80b-bf83c7deef23/291-1
Smith, Leisha: we'd identified in zebrafish fell. And then this was work done by Andreas 9580b482-17f5-4151-b80b-bf83c7deef23/291-2
Smith, Leisha: Salker and Agnieszka in collaboration with Jan Brosnans. 9580b482-17f5-4151-b80b-bf83c7deef23/291-3
Smith, Leisha: What we did was to then look at the complex. 9580b482-17f5-4151-b80b-bf83c7deef23/292-0
Smith, Leisha: Look. 9580b482-17f5-4151-b80b-bf83c7deef23/293-0
Smith, Leisha: Take human nodal pin code sequences, put them into zebrafish and lo and behold, 9580b482-17f5-4151-b80b-bf83c7deef23/293-1
Smith, Leisha: those pin codes from here still make it to the correct address in zebrafish. 9580b482-17f5-4151-b80b-bf83c7deef23/293-2
Smith, Leisha: So this machinery is concerned and recognized by the cellular factors. 9580b482-17f5-4151-b80b-bf83c7deef23/293-3
Smith, Leisha: We also made genome editing mutants in the component protein that recognizes the 9580b482-17f5-4151-b80b-bf83c7deef23/293-4
Smith, Leisha: pin code. 9580b482-17f5-4151-b80b-bf83c7deef23/294-0
Smith, Leisha: And and in humans we see that there's elevation of the protein translation in 9580b482-17f5-4151-b80b-bf83c7deef23/294-1
Smith, Leisha: in human cells as well. So this machinery that we had identified 9580b482-17f5-4151-b80b-bf83c7deef23/294-2
Smith, Leisha: in zoofish appears to be conserved and it seems to to utilize similar elements and 9580b482-17f5-4151-b80b-bf83c7deef23/294-3
Smith, Leisha: we published this and of course. 9580b482-17f5-4151-b80b-bf83c7deef23/295-0
Smith, Leisha: This was celebrated with cake, as always. So around that time, 9580b482-17f5-4151-b80b-bf83c7deef23/295-1
Smith, Leisha: we also had some new students joining. Some of you may recognize Finn Lambert 9580b482-17f5-4151-b80b-bf83c7deef23/295-2
Smith, Leisha: here, who was in the Warwick. So the key work was done by Adreish and 9580b482-17f5-4151-b80b-bf83c7deef23/295-3
Smith, Leisha: Andreas, and Finn actually was part of the Warwick 9580b482-17f5-4151-b80b-bf83c7deef23/295-4
Smith, Leisha: Arab doctorate. 9580b482-17f5-4151-b80b-bf83c7deef23/296-0
Smith, Leisha: Program, which also you know I was able to to lead 9580b482-17f5-4151-b80b-bf83c7deef23/296-1
Smith, Leisha: first with Rob Cross and then with Mia and with the fantastic support of our PGR 9580b482-17f5-4151-b80b-bf83c7deef23/296-2
Smith, Leisha: team. So these are some of the students who I 9580b482-17f5-4151-b80b-bf83c7deef23/296-3
Smith, Leisha: went to to meet in Singapore a couple of years back and you recognize Selena here. 9580b482-17f5-4151-b80b-bf83c7deef23/297-0
Smith, Leisha: And there's Edgar, who was in my lab, and there's Paulina. 9580b482-17f5-4151-b80b-bf83c7deef23/297-1
Smith, Leisha: So in addition to my lab, it's been really nice to see these young 9580b482-17f5-4151-b80b-bf83c7deef23/297-2
Smith, Leisha: people on their journeys. So the pin code that we identified in 9580b482-17f5-4151-b80b-bf83c7deef23/297-3
Smith, Leisha: noodle is found not only in in the growth factor itself, but also in. 9580b482-17f5-4151-b80b-bf83c7deef23/298-0
Smith, Leisha: its inhibitor, its receptor, and intracellular components. So, 9580b482-17f5-4151-b80b-bf83c7deef23/298-1
Smith, Leisha: there's a shared pin code in all these proper components, 9580b482-17f5-4151-b80b-bf83c7deef23/298-2
Smith, Leisha: suggesting that they might be regulated together uh in some way. So, 9580b482-17f5-4151-b80b-bf83c7deef23/298-3
Smith, Leisha: we then try to understand how this works, and this is very recent work by Adminshka 9580b482-17f5-4151-b80b-bf83c7deef23/298-4
Smith, Leisha: and 9580b482-17f5-4151-b80b-bf83c7deef23/299-0
Smith, Leisha: Andreas again. So they looked at this mutant Y box one 9580b482-17f5-4151-b80b-bf83c7deef23/299-1
Smith, Leisha: where this left-sided expression of noodle is altered in the mutant. 9580b482-17f5-4151-b80b-bf83c7deef23/299-2
Smith, Leisha: So it becomes either right-sided or bilateral and what that means for these 9580b482-17f5-4151-b80b-bf83c7deef23/299-3
Smith, Leisha: for these embryos. So essentially that that French flag is 9580b482-17f5-4151-b80b-bf83c7deef23/299-4
Smith, Leisha: altered. 9580b482-17f5-4151-b80b-bf83c7deef23/300-0
Smith, Leisha: The pattern is altered in this way, and what that means is that the heart, 9580b482-17f5-4151-b80b-bf83c7deef23/300-1
Smith, Leisha: in addition to having the wrong position, and I'm trying to find my mouse here. 9580b482-17f5-4151-b80b-bf83c7deef23/301-0
Smith, Leisha: How do I? 9580b482-17f5-4151-b80b-bf83c7deef23/302-0
Smith, Leisha: Find my mouse off. There it is. So normally you would have blood flow 9580b482-17f5-4151-b80b-bf83c7deef23/302-1
Smith, Leisha: from the A. 9580b482-17f5-4151-b80b-bf83c7deef23/304-0
Smith, Leisha: There we go. So this is the fish part at about five 9580b482-17f5-4151-b80b-bf83c7deef23/304-1
Smith, Leisha: days. Um There's the atrium, there's the ventricle, 9580b482-17f5-4151-b80b-bf83c7deef23/304-2
Smith, Leisha: and here is the AV canal. You can see individual blood cells moving 9580b482-17f5-4151-b80b-bf83c7deef23/304-3
Smith, Leisha: through, and normally the valve would get shut. 9580b482-17f5-4151-b80b-bf83c7deef23/304-4
Smith, Leisha: But in these mutants, in the proteins. 9580b482-17f5-4151-b80b-bf83c7deef23/306-0
Smith, Leisha: Team that recognizes the pin code. You can see that the blood flows, 9580b482-17f5-4151-b80b-bf83c7deef23/306-1
Smith, Leisha: flows back and it flushes back and forth and it appears like we have a heart valve 9580b482-17f5-4151-b80b-bf83c7deef23/306-2
Smith, Leisha: defect and then Adnishka then went on to do analysis. 9580b482-17f5-4151-b80b-bf83c7deef23/307-0
Smith, Leisha: And this was work done together with Michael Smith and his group. 9580b482-17f5-4151-b80b-bf83c7deef23/307-1
Smith, Leisha: And actually this is very similar to human valve defects. 9580b482-17f5-4151-b80b-bf83c7deef23/307-2
Smith, Leisha: And so this was collaborative work that we did. 9580b482-17f5-4151-b80b-bf83c7deef23/307-3
Smith, Leisha: Jan Grocken helped us identify the PIN code. One way did the functional analysis 9580b482-17f5-4151-b80b-bf83c7deef23/308-0
Smith, Leisha: those elements. And Mike's let me help us with a lot of 9580b482-17f5-4151-b80b-bf83c7deef23/308-1
Smith, Leisha: the heart genesis analysis. So this element and this paper that we 9580b482-17f5-4151-b80b-bf83c7deef23/308-2
Smith, Leisha: found in is present in multiple components of the pathway, 9580b482-17f5-4151-b80b-bf83c7deef23/308-3
Smith, Leisha: and is crucial not only for positioning of the heart, 9580b482-17f5-4151-b80b-bf83c7deef23/308-4
Smith, Leisha: but also for for development of the and function. 9580b482-17f5-4151-b80b-bf83c7deef23/309-0
Smith, Leisha: Of the of the mouth. So and this is of course the cake that we 9580b482-17f5-4151-b80b-bf83c7deef23/309-1
Smith, Leisha: had following this. So this this. 9580b482-17f5-4151-b80b-bf83c7deef23/310-0
Smith, Leisha: This pin code that we found in in zebrafish noodles is crucial not only for 9580b482-17f5-4151-b80b-bf83c7deef23/310-1
Smith, Leisha: for zebrafish, it's found all the way to humans. Second, 9580b482-17f5-4151-b80b-bf83c7deef23/310-2
Smith, Leisha: this pin code is is shared by multiple components of the pathway noodle itself, 9580b482-17f5-4151-b80b-bf83c7deef23/310-3
Smith, Leisha: it's it's inhibitors, receptors and also the enzymes that 9580b482-17f5-4151-b80b-bf83c7deef23/310-4
Smith, Leisha: cleave it. 9580b482-17f5-4151-b80b-bf83c7deef23/311-0
Smith, Leisha: So all this builds on an initial transcriptional switch which actually 9580b482-17f5-4151-b80b-bf83c7deef23/311-1
Smith, Leisha: turns on synthesis of these RNAs and then these pin codes kick in and these allow 9580b482-17f5-4151-b80b-bf83c7deef23/311-2
Smith, Leisha: tuning of gene expression levels and this is crucial and it's also for sorting and 9580b482-17f5-4151-b80b-bf83c7deef23/311-3
Smith, Leisha: and transporting these signals to the right place. 9580b482-17f5-4151-b80b-bf83c7deef23/312-0
Smith, Leisha: OK, so they act at the right time. So this element that we identified 9580b482-17f5-4151-b80b-bf83c7deef23/312-1
Smith, Leisha: controls not only the distribution of the RNA, but also where it gets made, 9580b482-17f5-4151-b80b-bf83c7deef23/312-2
Smith, Leisha: how much gets made. And this is very crucial for patterning 9580b482-17f5-4151-b80b-bf83c7deef23/312-3
Smith, Leisha: of the embryo. So what happens if you have too much 9580b482-17f5-4151-b80b-bf83c7deef23/312-4
Smith, Leisha: model too soon? 9580b482-17f5-4151-b80b-bf83c7deef23/313-0
Smith, Leisha: And what happens is, so this is a little fish embryo at about 9580b482-17f5-4151-b80b-bf83c7deef23/313-1
Smith, Leisha: a day old. If you have too much noodle too soon, 9580b482-17f5-4151-b80b-bf83c7deef23/313-2
Smith, Leisha: so in our mutant where the RNA fails to get to the correct address and stays 9580b482-17f5-4151-b80b-bf83c7deef23/313-3
Smith, Leisha: stuck, you have too much noodle being made too 9580b482-17f5-4151-b80b-bf83c7deef23/313-4
Smith, Leisha: soon. And what happens there is that we have 9580b482-17f5-4151-b80b-bf83c7deef23/313-5
Smith, Leisha: very few embryonic progenitive cells. 9580b482-17f5-4151-b80b-bf83c7deef23/314-0
Smith, Leisha: Instead, you have a lot of extramurionic cells. 9580b482-17f5-4151-b80b-bf83c7deef23/314-1
Smith, Leisha: So what that means is you have a very small fetus and a very large placenta. 9580b482-17f5-4151-b80b-bf83c7deef23/314-2
Smith, Leisha: And of course this is not going to survive. 9580b482-17f5-4151-b80b-bf83c7deef23/314-3
Smith, Leisha: And this is where I'm the students who work here. 9580b482-17f5-4151-b80b-bf83c7deef23/314-4
Smith, Leisha: So Leo Wong and Becky Leach were the key people who did this. 9580b482-17f5-4151-b80b-bf83c7deef23/315-0
Smith, Leisha: You identified another mutant within this pathway where instead of having a single 9580b482-17f5-4151-b80b-bf83c7deef23/315-1
Smith, Leisha: layer of nuclei that formed the extra-ending neonic tissue, and again, 9580b482-17f5-4151-b80b-bf83c7deef23/315-2
Smith, Leisha: you know, because you can see how this 9580b482-17f5-4151-b80b-bf83c7deef23/315-3
Smith, Leisha: placenta-like structure forms in living embryos in real time, 9580b482-17f5-4151-b80b-bf83c7deef23/315-4
Smith, Leisha: we are having to do any invasive experiments, whereas. 9580b482-17f5-4151-b80b-bf83c7deef23/316-0
Smith, Leisha: You know, if you were bucking with a mammal or with 9580b482-17f5-4151-b80b-bf83c7deef23/316-1
Smith, Leisha: humans, you'd be doing very invasive work. So this allows us to study this process 9580b482-17f5-4151-b80b-bf83c7deef23/316-2
Smith, Leisha: in a very simplified system, but in vivo in real time as it's 9580b482-17f5-4151-b80b-bf83c7deef23/316-3
Smith, Leisha: happening. And these are the key people who did the 9580b482-17f5-4151-b80b-bf83c7deef23/316-4
Smith, Leisha: early work. And this has been continued with our 9580b482-17f5-4151-b80b-bf83c7deef23/316-5
Smith, Leisha: postdoc Heda, who I'm very pleased with one of the best 9580b482-17f5-4151-b80b-bf83c7deef23/317-0
Smith, Leisha: Talk award last week at the LA Nest symposium. 9580b482-17f5-4151-b80b-bf83c7deef23/317-1
Smith, Leisha: So she's looking at how membranes and the cytoskeletonal remodel perform this extra 9580b482-17f5-4151-b80b-bf83c7deef23/317-2
Smith, Leisha: embryonic cell type and our collaborators in this work are listed here and we 9580b482-17f5-4151-b80b-bf83c7deef23/317-3
Smith, Leisha: continue to work on this problem. 9580b482-17f5-4151-b80b-bf83c7deef23/318-0
Smith, Leisha: So we've been looking at these mechanisms that control cell fate, how tissues form, 9580b482-17f5-4151-b80b-bf83c7deef23/318-1
Smith, Leisha: how signals are distributed. So these things happen at the right place, 9580b482-17f5-4151-b80b-bf83c7deef23/318-2
Smith, Leisha: right time, mostly in the embryo, but a lot of our our current work is also 9580b482-17f5-4151-b80b-bf83c7deef23/318-3
Smith, Leisha: looking at. 9580b482-17f5-4151-b80b-bf83c7deef23/319-0
Smith, Leisha: Oh goodness, there we go. So we're also looking at the germline and 9580b482-17f5-4151-b80b-bf83c7deef23/319-1
Smith, Leisha: I'm showing you a beautiful movie taken by Elias Zalka where he's looking at how 9580b482-17f5-4151-b80b-bf83c7deef23/319-2
Smith, Leisha: the germline, the cells that will give rise to the next 9580b482-17f5-4151-b80b-bf83c7deef23/319-3
Smith, Leisha: generation, how do they get, how do they form and how do you? 9580b482-17f5-4151-b80b-bf83c7deef23/320-0
Smith, Leisha: How do RNAs control this process? So this is work that Andreas and Maria 9580b482-17f5-4151-b80b-bf83c7deef23/320-1
Smith, Leisha: have been trying to work out. Again, using the power of live imaging in 9580b482-17f5-4151-b80b-bf83c7deef23/320-2
Smith, Leisha: zebrafish, manipulating the cytoskeleton, looking at many of these mutants that we 9580b482-17f5-4151-b80b-bf83c7deef23/320-3
Smith, Leisha: have generated over the years. 9580b482-17f5-4151-b80b-bf83c7deef23/321-0
Smith, Leisha: Understand how the GM line seems at the right place, right time. 9580b482-17f5-4151-b80b-bf83c7deef23/321-1
Smith, Leisha: How do you give rise to the next generation? OK, and we're also looking at. 9580b482-17f5-4151-b80b-bf83c7deef23/321-2
Smith, Leisha: So there's Andreas. In addition to establishing imaging and 9580b482-17f5-4151-b80b-bf83c7deef23/321-3
Smith, Leisha: the tools, he's also been crucial for training 9580b482-17f5-4151-b80b-bf83c7deef23/321-4
Smith, Leisha: people not only in my own lab, but also. 9580b482-17f5-4151-b80b-bf83c7deef23/322-0
Smith, Leisha: All the visitors that we've had through the years, here he is with Azan, 9580b482-17f5-4151-b80b-bf83c7deef23/322-1
Smith, Leisha: who is a visitor from Qatar University who came to us this summer to learn how 9580b482-17f5-4151-b80b-bf83c7deef23/322-2
Smith, Leisha: to image and he's been very helpful. So Andreas is is looking at how does the 9580b482-17f5-4151-b80b-bf83c7deef23/322-3
Smith, Leisha: germline get established, how does it form and they're 9580b482-17f5-4151-b80b-bf83c7deef23/322-4
Smith, Leisha: collaborating with with. 9580b482-17f5-4151-b80b-bf83c7deef23/323-0
Smith, Leisha: at the Engineering Department at Cambridge University and the Rouse who's 9580b482-17f5-4151-b80b-bf83c7deef23/323-1
Smith, Leisha: a joint student and they're using both experimental and mathematical approaches 9580b482-17f5-4151-b80b-bf83c7deef23/323-2
Smith, Leisha: to understand how the shape of forces or free of cytosol influences the 9580b482-17f5-4151-b80b-bf83c7deef23/324-0
Smith, Leisha: Distribution of these granules that are important for forming the germline in the 9580b482-17f5-4151-b80b-bf83c7deef23/324-1
Smith, Leisha: next generation. And last but not the least, 9580b482-17f5-4151-b80b-bf83c7deef23/324-2
Smith, Leisha: 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
Smith, Leisha: key structure in this in early oocytes. In all vertebrates at early stages, 9580b482-17f5-4151-b80b-bf83c7deef23/324-4
Smith, Leisha: there's a structure called the Balbiani body which is. 9580b482-17f5-4151-b80b-bf83c7deef23/325-0
Smith, Leisha: Discovered 160 years ago, we don't really understand what it does 9580b482-17f5-4151-b80b-bf83c7deef23/325-1
Smith, Leisha: and how it functions. And many of the components in the 9580b482-17f5-4151-b80b-bf83c7deef23/325-2
Smith, Leisha: biogenic body then get distributed either to the germ plasm or similar to neuron 9580b482-17f5-4151-b80b-bf83c7deef23/325-3
Smith, Leisha: get distributed to specific locations in the eggs. 9580b482-17f5-4151-b80b-bf83c7deef23/325-4
Smith, Leisha: So we basically moved the clock back. We're now going back. 9580b482-17f5-4151-b80b-bf83c7deef23/326-0
Smith, Leisha: to the very beginning, early stages of when eggs are made to 9580b482-17f5-4151-b80b-bf83c7deef23/326-1
Smith, Leisha: understand how these RNAs get to where they are and how they function later on 9580b482-17f5-4151-b80b-bf83c7deef23/326-2
Smith, Leisha: in in the egg and the embryo. We're also taking a comparative approach. 9580b482-17f5-4151-b80b-bf83c7deef23/326-3
Smith, Leisha: Our newest model organism is the mangrove kidney fish. 9580b482-17f5-4151-b80b-bf83c7deef23/327-0
Smith, Leisha: And this is work being done by a new student in the lab. 9580b482-17f5-4151-b80b-bf83c7deef23/327-1
Smith, Leisha: And together we hope to understand the basis of how oocytes develop and how the 9580b482-17f5-4151-b80b-bf83c7deef23/327-2
Smith, Leisha: Indianic axis forms. And perhaps I'll be able to go back to 9580b482-17f5-4151-b80b-bf83c7deef23/327-3
Smith, Leisha: address that original question that I had. 9580b482-17f5-4151-b80b-bf83c7deef23/328-0
Smith, Leisha: What is normal RNA doing in the egg anyway? 9580b482-17f5-4151-b80b-bf83c7deef23/328-1
Smith, Leisha: And what does that have to do with how you put put the egg? 9580b482-17f5-4151-b80b-bf83c7deef23/328-2
Smith, Leisha: So how is this relevant? Well, the balbani body is present in humans as 9580b482-17f5-4151-b80b-bf83c7deef23/328-3
Smith, Leisha: well. And of course we can't do these 9580b482-17f5-4151-b80b-bf83c7deef23/328-4
Smith, Leisha: manipulations in in human research, but the fish is very accessible to these 9580b482-17f5-4151-b80b-bf83c7deef23/328-5
Smith, Leisha: and we have all the 9580b482-17f5-4151-b80b-bf83c7deef23/329-0
Smith, Leisha: now. So I'll give you some of the the lab 9580b482-17f5-4151-b80b-bf83c7deef23/329-1
Smith, Leisha: outings that we've had over the years here at work. 9580b482-17f5-4151-b80b-bf83c7deef23/329-2
Smith, Leisha: We can see Christmas over the years, some lab trips to the to the Maldon Hills, 9580b482-17f5-4151-b80b-bf83c7deef23/329-3
Smith, Leisha: Camembert Castle, Coventry Cathedral, and of course we're a lab that eats well. 9580b482-17f5-4151-b80b-bf83c7deef23/330-0
Smith, Leisha: And here are all the talented people who make this possible. 9580b482-17f5-4151-b80b-bf83c7deef23/330-1
Smith, Leisha: So here are the students, their examiners, collaborators without whom all of this 9580b482-17f5-4151-b80b-bf83c7deef23/330-2
Smith, Leisha: would be impossible. The many trainees who've come through the 9580b482-17f5-4151-b80b-bf83c7deef23/330-3
Smith, Leisha: lab over the years and. 9580b482-17f5-4151-b80b-bf83c7deef23/331-0
Smith, Leisha: You know, I I also want to acknowledge the 9580b482-17f5-4151-b80b-bf83c7deef23/331-1
Smith, Leisha: community, not just here at work and the UK, 9580b482-17f5-4151-b80b-bf83c7deef23/331-2
Smith, Leisha: but also throughout the world, who've been very supportive of our work, 9580b482-17f5-4151-b80b-bf83c7deef23/331-3
Smith, Leisha: very generous in sharing their relations. And you know, 9580b482-17f5-4151-b80b-bf83c7deef23/331-4
Smith, Leisha: when I started out as a student, I never learned that I would one day be 9580b482-17f5-4151-b80b-bf83c7deef23/331-5
Smith, Leisha: the president of the international 9580b482-17f5-4151-b80b-bf83c7deef23/332-0
Smith, Leisha: Society. I just got elected last month. This is a society with about 1100 overall 9580b482-17f5-4151-b80b-bf83c7deef23/332-1
Smith, Leisha: members in 60 labs worldwide. So this has really been quite a journey 9580b482-17f5-4151-b80b-bf83c7deef23/332-2
Smith, Leisha: and I'm really very pleased that that I've had all these people that I could 9580b482-17f5-4151-b80b-bf83c7deef23/332-3
Smith, Leisha: lean on throughout every stage of my career. 9580b482-17f5-4151-b80b-bf83c7deef23/333-0
Smith, Leisha: And I should also leave you with the names of all the people who've actually 9580b482-17f5-4151-b80b-bf83c7deef23/333-1
Smith, Leisha: done all the work, the funders in Singapore, 9580b482-17f5-4151-b80b-bf83c7deef23/333-2
Smith, Leisha: and I've got many, many collaborators and of course. 9580b482-17f5-4151-b80b-bf83c7deef23/334-0
Smith, Leisha: Warwick there you know we are continuing to work on these the you know there are 9580b482-17f5-4151-b80b-bf83c7deef23/334-1
Smith, Leisha: many, many collaborators not just in Singapore 9580b482-17f5-4151-b80b-bf83c7deef23/334-2
Smith, Leisha: but worldwide and and and at Warwick the main facilities most of all the fish 9580b482-17f5-4151-b80b-bf83c7deef23/334-3
Smith, Leisha: facility but also the imaging, I mean the outstanding imaging facilities 9580b482-17f5-4151-b80b-bf83c7deef23/334-4
Smith, Leisha: that we have. 9580b482-17f5-4151-b80b-bf83c7deef23/335-0
Smith, Leisha: Potomax and the others. And you know, we were very fortunate to have next door 9580b482-17f5-4151-b80b-bf83c7deef23/335-1
Smith, Leisha: and and Teresa in particular has been like really superb in in helping us every 9580b482-17f5-4151-b80b-bf83c7deef23/335-2
Smith, Leisha: step of the way. Bernardo helped us with imaging men in 9580b482-17f5-4151-b80b-bf83c7deef23/335-3
Smith, Leisha: the in the early years as well. So all these people and of course all our 9580b482-17f5-4151-b80b-bf83c7deef23/335-4
Smith, Leisha: funders over the years, we were. 9580b482-17f5-4151-b80b-bf83c7deef23/336-0
Smith, Leisha: and DBSRC have supported my work and in the early stages of the Welcome Upwork 9580b482-17f5-4151-b80b-bf83c7deef23/336-1
Smith, Leisha: Quantitative Biomedicine program also the seed grants. 9580b482-17f5-4151-b80b-bf83c7deef23/336-2
Smith, Leisha: You know we don't see enough of these anymore and it would be really nice to 9580b482-17f5-4151-b80b-bf83c7deef23/336-3
Smith, Leisha: see those kinds of small grants that would then allow you to to start new 9580b482-17f5-4151-b80b-bf83c7deef23/336-4
Smith, Leisha: projects and then 9580b482-17f5-4151-b80b-bf83c7deef23/337-0
Smith, Leisha: Take them to the next level, the medical and life sciences research 9580b482-17f5-4151-b80b-bf83c7deef23/337-1
Smith, Leisha: fund, the many doctoral programs at work and of 9580b482-17f5-4151-b80b-bf83c7deef23/337-2
Smith, Leisha: course. 9580b482-17f5-4151-b80b-bf83c7deef23/339-0
Smith, Leisha: 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
Smith, Leisha: IBRB third floor. And you know we have this great lab rats 9580b482-17f5-4151-b80b-bf83c7deef23/339-2
Smith, Leisha: team which is very competitive and we we like to to compete in the tri-grade 9580b482-17f5-4151-b80b-bf83c7deef23/339-3
Smith, Leisha: events and where's that cup? It's going. 9580b482-17f5-4151-b80b-bf83c7deef23/340-0
Smith, Leisha: OK. We're very proud of our, our, our tri-made binning cups. 9580b482-17f5-4151-b80b-bf83c7deef23/340-1
Smith, Leisha: So come see that on the third floor when you have a chance. So, 9580b482-17f5-4151-b80b-bf83c7deef23/340-2
Smith, Leisha: so thank you very much. It's been a pleasure to work with 9580b482-17f5-4151-b80b-bf83c7deef23/340-3
Smith, Leisha: everyone and I look forward to many more years of of trying to figure out. 9580b482-17f5-4151-b80b-bf83c7deef23/341-0
Smith, Leisha: Are the animals how to put the head? So thank you. 9580b482-17f5-4151-b80b-bf83c7deef23/343-0
Smith, Leisha: Fantastic and inspiring talk. We've got time for a couple of questions. 9580b482-17f5-4151-b80b-bf83c7deef23/343-1
Smith, Leisha: I'm going to take Dean's prerogative to start off with the first question and 9580b482-17f5-4151-b80b-bf83c7deef23/343-2
Smith, Leisha: it's really I think I took three things away from your. 9580b482-17f5-4151-b80b-bf83c7deef23/344-0
Smith, Leisha: You know, firstly the complexity, the depth and the excellence of the 9580b482-17f5-4151-b80b-bf83c7deef23/344-1
Smith, Leisha: science that you're doing. Secondly, the collaboration of the networks came 9580b482-17f5-4151-b80b-bf83c7deef23/344-2
Smith, Leisha: through really powerful. And thirdly, the role that you've played as a mentor 9580b482-17f5-4151-b80b-bf83c7deef23/344-3
Smith, Leisha: for the generation of scientists that that will follow you. 9580b482-17f5-4151-b80b-bf83c7deef23/344-4
Smith, Leisha: So picking the middle one of those. 9580b482-17f5-4151-b80b-bf83c7deef23/345-0
Smith, Leisha: Around collaboration is how have you managed to create and sustain such 9580b482-17f5-4151-b80b-bf83c7deef23/345-1
Smith, Leisha: networks and what pace would you have for colleagues in terms of emulating like 9580b482-17f5-4151-b80b-bf83c7deef23/345-2
Smith, Leisha: that? Yeah. So in the early years, of course, 9580b482-17f5-4151-b80b-bf83c7deef23/345-3
Smith, Leisha: collaboration is happening because of the environment I was in, you know, Chris, 9580b482-17f5-4151-b80b-bf83c7deef23/345-4
Smith, Leisha: as soon as he saw. 9580b482-17f5-4151-b80b-bf83c7deef23/346-0
Smith, Leisha: Our left side of gene expression who got on the phone because that's what you did 9580b482-17f5-4151-b80b-bf83c7deef23/346-1
Smith, Leisha: those days and talk to people who are working on on the mouse and so on. 9580b482-17f5-4151-b80b-bf83c7deef23/346-2
Smith, Leisha: And we could, you know, that just happened because of where I was. 9580b482-17f5-4151-b80b-bf83c7deef23/346-3
Smith, Leisha: And then I initiated the work on zebrafish and then carried that on and 9580b482-17f5-4151-b80b-bf83c7deef23/346-4
Smith, Leisha: then worked collaboratively with the people in the state. 9580b482-17f5-4151-b80b-bf83c7deef23/348-0
Smith, Leisha: And also in Singapore to take that forward. And of course, again, 9580b482-17f5-4151-b80b-bf83c7deef23/348-1
Smith, Leisha: the environment played a role because I was in this institute which forteously 9580b482-17f5-4151-b80b-bf83c7deef23/348-2
Smith, Leisha: had people who were working as advisors who could then put me in touch with that. 9580b482-17f5-4151-b80b-bf83c7deef23/348-3
Smith, Leisha: So I think it's really a combination of one is we cannot do everything alone. 9580b482-17f5-4151-b80b-bf83c7deef23/350-0
Smith, Leisha: 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
Smith, Leisha: people who can add value to your own work, really things that you cannot do. 9580b482-17f5-4151-b80b-bf83c7deef23/350-2
Smith, Leisha: And together you solve more than you would never be able to alone. 9580b482-17f5-4151-b80b-bf83c7deef23/351-0
Smith, Leisha: And and I guess these days you do need to be interdisciplinary. 9580b482-17f5-4151-b80b-bf83c7deef23/351-1
Smith, Leisha: Now I come from a classical zoology training. 9580b482-17f5-4151-b80b-bf83c7deef23/351-2
Smith, Leisha: What do I know about simulations and modeling? 9580b482-17f5-4151-b80b-bf83c7deef23/351-3
Smith, Leisha: So I do see these this expertise out and that has really worked and yeah, 9580b482-17f5-4151-b80b-bf83c7deef23/351-4
Smith, Leisha: I mean circumstances. 9580b482-17f5-4151-b80b-bf83c7deef23/352-0
Smith, Leisha: Not knowing enough. And then of course the environment. 9580b482-17f5-4151-b80b-bf83c7deef23/352-1
Smith, Leisha: And Warwick's a great place to do collaborative interdisciplinary work, 9580b482-17f5-4151-b80b-bf83c7deef23/352-2
Smith, Leisha: 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
Smith, Leisha: questions in the audience. 9580b482-17f5-4151-b80b-bf83c7deef23/353-0
Smith, Leisha: Not sure if Claire or colleagues consider that Leslie has one Leslie. 9580b482-17f5-4151-b80b-bf83c7deef23/355-0
Smith, Leisha: Just because there's been a non my amendments, 9580b482-17f5-4151-b80b-bf83c7deef23/355-1
Smith, Leisha: 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
Smith, Leisha: just the president-elect of the executive prime. However, 9580b482-17f5-4151-b80b-bf83c7deef23/355-3
Smith, Leisha: I'm aware that obviously the government has been expansion of the number of 9580b482-17f5-4151-b80b-bf83c7deef23/355-4
Smith, Leisha: publications. 9580b482-17f5-4151-b80b-bf83c7deef23/356-0
Smith, Leisha: In the last decade using zebrafish models, but zebrafish and tropical fish. 9580b482-17f5-4151-b80b-bf83c7deef23/356-1
Smith, Leisha: So from a climate perspective, maintaining them costs more than 9580b482-17f5-4151-b80b-bf83c7deef23/356-2
Smith, Leisha: maintaining coal to fish. So my question is. 9580b482-17f5-4151-b80b-bf83c7deef23/357-0
Smith, Leisha: Why? Why have we not identified the more 9580b482-17f5-4151-b80b-bf83c7deef23/357-1
Smith, Leisha: climate friendly alternative? No, no, no. I'll just join another society. 9580b482-17f5-4151-b80b-bf83c7deef23/357-2
Smith, Leisha: Easier to do that. 9580b482-17f5-4151-b80b-bf83c7deef23/358-0
Smith, Leisha: Actually, when we go to the fish meetings, we welcome other fish as well. 9580b482-17f5-4151-b80b-bf83c7deef23/358-1
Smith, Leisha: So we recently started working on this mangrove killifish, 9580b482-17f5-4151-b80b-bf83c7deef23/358-2
Smith, Leisha: which has a wide geographical range and is extremely tolerant of of a temperature 9580b482-17f5-4151-b80b-bf83c7deef23/358-3
Smith, Leisha: range. So it grows in mangroves all the way from 9580b482-17f5-4151-b80b-bf83c7deef23/358-4
Smith, Leisha: freshwater to the ocean. 9580b482-17f5-4151-b80b-bf83c7deef23/359-0
Smith, Leisha: Wide tolerance and this is our climate change model going into the future. 9580b482-17f5-4151-b80b-bf83c7deef23/359-1
Smith, Leisha: And because we just know so much about zebrafish, 9580b482-17f5-4151-b80b-bf83c7deef23/359-2
Smith, Leisha: we're using that for comparative studies and use that as sort of a foundation. 9580b482-17f5-4151-b80b-bf83c7deef23/359-3
Smith, Leisha: But yes, I fully appreciate your question and we 9580b482-17f5-4151-b80b-bf83c7deef23/359-4
Smith, Leisha: are thinking about this, so going forward. 9580b482-17f5-4151-b80b-bf83c7deef23/360-0
Smith, Leisha: We are going to look at, you know, what does climate change do to the body 9580b482-17f5-4151-b80b-bf83c7deef23/360-1
Smith, Leisha: plan, to the reproductive system? You know, 9580b482-17f5-4151-b80b-bf83c7deef23/360-2
Smith, Leisha: fish are the most important source of protein in the world, 9580b482-17f5-4151-b80b-bf83c7deef23/360-3
Smith, Leisha: and all these changes are impacting fish populations worldwide. 9580b482-17f5-4151-b80b-bf83c7deef23/360-4
Smith, Leisha: And we want to look at how these extremophiles are somehow able to to. 9580b482-17f5-4151-b80b-bf83c7deef23/361-0
Smith, Leisha: Take this on board and still maintain their reproductive capacity and maintain 9580b482-17f5-4151-b80b-bf83c7deef23/361-1
Smith, Leisha: continuity. 9580b482-17f5-4151-b80b-bf83c7deef23/362-0
Smith, Leisha: So hopefully learning more from a comparative approach, yeah. 9580b482-17f5-4151-b80b-bf83c7deef23/363-0
Smith, Leisha: Lovely. Thank you, Leslie. I'm not seeing hands raised elsewhere. 9580b482-17f5-4151-b80b-bf83c7deef23/363-1
Smith, Leisha: We're getting clash. I think we've got one more. Yeah, judging. 9580b482-17f5-4151-b80b-bf83c7deef23/363-2
Smith, Leisha: I'm going to bring them out just for the help of the people that are online. 9580b482-17f5-4151-b80b-bf83c7deef23/364-0
Smith, Leisha: Thanks for that. You know, relationship. But is more and more. Thankfully, 9580b482-17f5-4151-b80b-bf83c7deef23/364-1
Smith, Leisha: as you say about climate change. 9580b482-17f5-4151-b80b-bf83c7deef23/366-0
Smith, Leisha: And because you know the heart of the is this idea that you have these these 9580b482-17f5-4151-b80b-bf83c7deef23/366-1
Smith, Leisha: proteins that connect together to form a physical and. 9580b482-17f5-4151-b80b-bf83c7deef23/367-0
Smith, Leisha: And I'm just wondering what happened when you look at killfish, 9580b482-17f5-4151-b80b-bf83c7deef23/367-1
Smith, Leisha: these different temperature, what happens to this in the works. 9580b482-17f5-4151-b80b-bf83c7deef23/367-2
Smith, Leisha: That is something that that that May has starting to explore. 9580b482-17f5-4151-b80b-bf83c7deef23/367-3
Smith, Leisha: She's looking at what happens to germline RNA complexes and yeah, that's. 9580b482-17f5-4151-b80b-bf83c7deef23/369-0
Smith, Leisha: In fact, she had a summer high school student work 9580b482-17f5-4151-b80b-bf83c7deef23/369-1
Smith, Leisha: with her looking at two different temperatures. 9580b482-17f5-4151-b80b-bf83c7deef23/369-2
Smith, Leisha: So this is ongoing right now. Yeah. 9580b482-17f5-4151-b80b-bf83c7deef23/370-0
Smith, Leisha: Thank you. 9580b482-17f5-4151-b80b-bf83c7deef23/372-0
Smith, Leisha: 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
Smith, Leisha: I'm going to present to you shortly, but just for you, you know, 9580b482-17f5-4151-b80b-bf83c7deef23/372-2
Smith, Leisha: many congratulations. Thank you. Thank you very much. 9580b482-17f5-4151-b80b-bf83c7deef23/373-0
Smith, Leisha: It is yours. 9580b482-17f5-4151-b80b-bf83c7deef23/376-0
Smith, Leisha: You've been waiting for. Thank you. It's very beautiful all the same. 9580b482-17f5-4151-b80b-bf83c7deef23/376-1
Smith, Leisha: Thank you. 9580b482-17f5-4151-b80b-bf83c7deef23/379-0
Smith, Leisha: OK. 9580b482-17f5-4151-b80b-bf83c7deef23/380-0
Smith, Leisha: You. 9580b482-17f5-4151-b80b-bf83c7deef23/382-0
Smith, Leisha: Yeah, yeah.