In fall 2015, ASCB awarded the first-ever ASCB-Gibco Emerging Leader Prizes to three cell biology researchers. ASCB introduced the prizes to honor not-yet-tenured independent investigators with outstanding scientific accomplishments and strong publication track records. The prizes were underwritten by Gibco, a brand of Thermo Fisher Scientific.
ASCB President Peter Walter invited each of the prize winners and each of the seven additional finalists to contribute an essay to the ASCB Newsletter. The writers were encouraged to provide a personal statement that articulates who they are, their science, and how they got into it; to describe their major scientific accomplishments; and to discuss their “dream results” and where they see themselves in the next five years.
This issue of the Newsletter features the essay of finalist Guangshuo Ou. Three essays appeared in the March/April 2016 issue and others will be published in coming issues.
Guangshuo Ou
I am an associate professor in the School of Life Sciences, Tsinghua University in Beijing, where I study neuroblast development using the nematode Caenorhabditis elegans as a model organism.
Guangshuo Ou
Tsinghua University
Neuroblast development typically involves asymmetric cell division, migration, apoptosis, and neurite growth, defects in which are implicated in neuronal disorders. My laboratory tackles old problems in neuroblast development with modern imaging, genetic, and biochemical approaches. We work on the C. elegans Q neuroblast lineage, which was initially described by Sulston and Horvitz in the 1970s and subsequently studied by Cynthia Kenyon and others using classic genetics to identify genes in the pathway. With the aid of my prior expertise in time-lapse microscopy of C. elegans neuronal cilia, I began to study Q cell development when I was a postdoctoral fellow with Ron Vale. I showed that we could learn still more about the Q cell by making movies to follow the dynamics of GFP-tagged molecular markers over time. Since 2011, my group has developed new tools to study the Q cell and advanced our understanding of cell migration and asymmetric division.
My lab devised efficient, rapid, and cost-effective methods to generate conditional knockouts in somatic cell lineages by expressing the programmable endonuclease TALEN or Cas9 with an inducible or tissue-specific promoter. These platforms facilitated the study of cell migration, cell division, neurite outgrowth, axonal transport, epithelial development, and ciliogenesis, showing that the platforms are versatile tools with which to address cell biological questions in live animals. The methodology enables the functional analysis of embryonically lethal genes in postembryonic cellular processes and provides the capacity to separate the manifold roles of a single gene in multiple cellular events.
We study how extracellular signals are transduced to the actin cytoskeleton during cell migration. We have uncovered a novel pathway in which Anillin transduces the RhoG signal to the actin cytoskeleton. Originally characterized as a cytokinetic scaffold protein, Anillin is redistributed to the leading edge and stabilizes F-actin by antagonizing the F-actin–severing activity of Cofilin, indicating that stabilization of the actin network is important for coherent motility. Using a similar strategy, we discovered that another actin-binding protein, Coronin, promotes F-actin disassembly in migrating cells of C. elegans. To understand the directionality of cell migration, we identified an evolutionarily conserved membrane protein, MIG-13, that functions autonomously to guide anterior Q cell migration, and we have recently uncovered two parallel pathways that respectively transduce the MIG-13 signal to WASP and the WAVE complex for Arp2/3 activation.
Our studies of Q cell asymmetric division showed that asymmetric accumulation of myosin II on one pole of a dividing Q cell can govern asymmetry in the size and fate of daughter cells, and we have isolated mutations defective in myosin asymmetry. We addressed the fate of the midbody after cell division in live animals. Q cell midbodies are released and subsequently internalized and degraded by a neighboring epithelial cell. This process requires apoptotic cell engulfment genes, and the externalized phosphatidylserine mediates the recognition between midbody and phagocyte. Interestingly, the midbody generated by the first division of the C. elegans embryo is subject to a similar mechanism for degradation, implying a common fate for midbodies in C. elegans.
Taken together, we have developed imaging and genetic tools to study Q cell development and obtained new information regarding cell migration and asymmetric cell division. In the course of our study of the Q cell, we realized that each cell shares common mechanisms but also has unique features in live animals. We will use similar strategies to extend our study to other cell types in C. elegans and hope to uncover the novel molecular and cellular pathways underlying metazoan development.
