The day he sat in on a developmental biology class and saw Yale geneticist Frank Ruddle diagramming embryogenesis in brightly colored chalk, then high school senior Matt Gibson knew he had found his calling. “Embryology and developmental biology are so visually appealing,” says Gibson, a Stowers Assistant Investigator since 2006. “And there is just something intrinsically captivating about how these processes are encoded by the genetic information in a single nucleus.”
The class had lit a spark, and Gibson began intensive undergraduate research at Yale with Drosophila geneticist Doug Kankel—Ruddle’s co-instructor—and was awarded a BS in biology in 1994. From there Gibson earned a Ph.D. in Zoology with geneticist Gerold Schubiger at University of Washington in 2001, where he studied development and regeneration of Drosophila imaginal discs, larval appendage primordia that ultimately give rise to the eyes, wings and legs of the adult fly.
The delicate structures of a wing cuticle of an adult fruit fly ready to emerge from the pupa were visualized in a scanning electron microscope.
Image: Gibson lab.
The importance of visualizing a biological process—whether in fruit fly wing primordia, the tentacles of a sea anemone, or the skin of a cucumber— has been a common theme in Gibson’s fascination with how dividing cells become regimented into highly organized layers known as epithelia.
“In biology, the first thing I am drawn to is aesthetics,” says Gibson. “From there the major attraction is to understand the genetic, molecular and physical mechanisms underlying the beauty of nature.” That fact is immediately apparent in figures from the Gibson Lab’s publications. Their images depict dynamic changes in the architecture of fluorescently-labeled epithelial cells filling a 3D space. Cell junctions glow green in web-like patterns dotted by royal blue nuclei, amid red markers indicating whether cells are thriving, dying, or growing in the wrong place in a mutant fly or sea anemone embryo.
As a postdoctoral fellow in the lab of renowned Drosophila geneticist Norbert Perrimon at Harvard Medical School, Gibson published a Science paper in 2005 that might have capped any successful postdoc’s career. In it, he demonstrated an unexpected role for the signaling molecule BMP in controlling the shape and fate of epithelial cells that would form the Drosophila wing. But Gibson, a recipient of a Jane Coffin Childs Memorial Fund postdoctoral fellowship, rapidly moved on to a very different venture: to define mathematical principles governing how polygonally-shaped cells pack into a proliferating epithelial sheet. “Hexagonal packing appears over and over in nature, as in honeycombs, but in epithelia we saw what could be a random assortment of polygonal forms,” says Gibson. “We wondered whether there was a cryptic order governing this seemingly random pattern of cell shapes—one that we could understand quantitatively.”
The starlet sea anemone (Nematostella vectensis) is an important model
mechanism for comparative genomics and developmental biology. Here, a juvenile at the 4-tentacle bud stage is shown. Tubulin is green, F-Actin is red, and nuclei are labeled blue.
Image: Gibson lab.
For this interdisciplinary problem, Gibson teamed up with Harvard computer scientist Radhika Nagpal, who he initially identified as a possible collaborator via a Google search. The two have since published a series of studies, starting with a 2006 Nature paper, showing how simple mathematical rules govern the arrangement and sidedness of epithelial cells.
“Our initial work showed that the combined processes of cell adhesion and cell division lead to emergence of a specific topological order,” says Gibson. “What was conceptually interesting is that no set of genes specifically regulates this—and in that sense there is a fundamental mathematical constraint which determines the structure of the biological system.” Nagpal and Gibson are still collaborating, and in 2011 published a theory paper in Cell showing how polygonal cell packing can feed-back and influence the spatial orientation of cell division in tissues as different as fruit fly larvae and cucumber epidermis.
With his lab established at the Stowers Institute, Gibson continues to work on numerous aspects of imaginal disc development, and is also branching out into comparative analysis of epithelial morphogenesis and growth control. For that, his group has turned to the tentacles of a simple metazoan, the sea anemone Nematostella vectensis. Despite the fact that Nematostella occupies a basal phylogenetic position (similar to corals and jellyfish), its genome exhibits a surprising degree of complexity and similarity to the vertebrate genome. With its mass of feeding tentacles glowing red with their own fluorescence, Nematostella also just happens to be highly photogenic.
Thus far the Gibson Lab has published two papers using the Nematostella model system, the most recent a 2011 study in Current Biology showing that shuttling movements of nuclei in dividing epithelial cells in the Nematostella tentacle are comparable to those seen in epithelia of the fly wing imaginal disc and the vertebrate neural tube.
“Doing science is an intensely creative process not totally unlike the arts,” says Gibson, who has written songs on guitar since his high school days. “It requires that you mentally envision a testable hypothesis of how a biological system works long before you know how the final picture is going to appear.”
Asked why he chose Stowers to start his independent career, Gibson immediately cites the unique freedom for a junior investigator to move in new directions. He notes frequent calls for risk-taking in biological research, but conventional funding sources are conservative, making it extremely difficult for a young investigator to try anything new.
“Before I started the Nematostella projects I told (scientific director) Robb Krumlauf that I’d never seen these animals and couldn’t guarantee anything would come of it, and he said, ‘That’s why you are here,’” says Gibson. “Here, risk gets a little more than lip service—it’s actively encouraged.”