An Interview with Professor Gian Garriga on Asymmetric Cell Divisions: Distinct Fates of Daughter Cells

A n I nterview with P rofessor G ian G arriga on A symmetric C ell D ivisions : D istinct F ates of D aughter C ells B S J Manraj Gill, Tiffany Nguyen, Georgia Kirn Dr. Gian Garriga is a Professor of Genetics, Genomics and Development in the department of Molecular and Cell Biology at the University of California, Berkeley. Professor Garriga’s interest in understanding the C. elegans nervous system has led to a study into more fundamental questions of cell biology. In this interview, we talk about one such topic, asymmetric cell division, and discuss not only Figure #1. Professor Gian its molecular basis but also its role Garriga in apoptosis and stem cell differentiation. Berkeley Scientific Journal: How did you first get involved in your field of research? Gian Garriga: After college I was pretty sick of school so I actually did other things for many years and then sort of accidently met some people and ended up going to graduate school. I was a molecular biologist and a biochemist. As a graduate student, I studied RNA splicing. At the end of that, the original plan was to go and get a job in the industry but I thought, “Well, I could put that off.” I looked around for things to do as a post-doc and thought that it would be good fun to work on something that really wasn’t understood at all. At the time, people didn’t really know how the nervous system was developed. It was very different from what I had done previously so I looked at different organisms where people were studying this. And even though I didn’t do genetics as a graduate student, I sort of appreciated it. It was really a choice between doing something in drosophila or C. elegans (Caenorhabditis elegans). C. elegans were this sort of newer organism in the sense that people had only recently been studying it. And it was also very simple and people appreciated that and you could freeze it. [That’s something] you couldn’t do with flies and I’m not that organized so something I could freeze was better. BSJ: And what led to this focus into cell division? GG: That began just when I started working as a post-doc, I worked on a pair of motor neurons that innervated egg- laying muscles and stimulated hermaphrodites to C. elegans. They stimulated hermaphrodites to lay eggs. So, I started to Figure #2. Caenorhabditis elegans screen for mutants that were defective in various aspects of the development of these neurons. We identified genes that were involved in all kinds of aspects: from how the neurons were generated and how cells migrated early in their development to how they later send out axons. Just because of the genes that I found most interesting when I came to Berkeley, I focused on asymmetric cell division. Migrating cells would polarize growth cones, which are the ends of axons that are migrating. And then these cells that divide asymmetrically give rise to different types of cells during development. It’s sort of a polarity issue. Polarity drives all of these processes, so that’s what we’ve been working on pretty much since I’ve been here. Which is a long time… BSJ: Why study C. elegans specifically for this question of cell division? GG: C. elegans is the only animal where we know it’s development in detail. People in the 1970’s and 1980’s began to just follow the divisions of C. elegans because it’s simple and transparent. You didn’t need to have any sort of special methods. And you could observe the cells divide. John Salston, who won a Nobel Prize for this, was able to follow all of the divisions in C. elegans. They’re stereotyped between one organism and the next. The lineage is invariant and you can predict where any cell has been, in terms of its ancestry. You know if it’s a precursor cell, it’s going to divide. And if it’s not, you can tell what type of cell it is: if it a neuron, if it’s a muscle cell, or if it is a cell that’s going to die. One of the things we study is apoptosis. To understand how fate is specified, and understand the process of asymmetric cell division, you really have to understand this lineage and how that’s generated. BSJ: What exactly is asymmetric cell division? GG: You can think of how you specify cells in two different ways. I’m going to pick flies as examples here. When I first came to Berkeley, there was a lot of work in Jerry Rubin’s lab on fly eye development. The way that works is there’s an undifferentiated epithelium as there’s a morphogen that 31 • B erkeley S cientific J ournal • S ymmetry • F all 2015 • V olume 20 • I ssue 1