Last year Shane Hutson received a prestigious award for young researchers from the National Science Foundation to study the physical forces that drive biological development
By David F. Salisbury
The vital process that transforms the identical cells in a fertilized egg into a multi-cellular embryo with a complicated shape and dozens of different cell types involves a surprising amount of movement: As development proceeds, cells move hither and yon in a complex choreography for reasons that largely remain mysterious.
Shane Hutson, assistant professor of physics at Vanderbilt University and fellow with the Vanderbilt Institute for Integrative Biosystem Research and Education, is one of a small group of researchers who are studying the nature of the forces that cause these cell movements. He just received a five-year, $833,000 CAREER award from the National Science Foundation to support his studies of the underlying mechanisms that drive these motions in the development of fruit fly embryos.
The Faculty Early Career Development awards are considered NSF's most prestigious honor for junior faculty members. They are given to exceptionally promising college and university junior faculty who are committed to the integration of research and education and who are most likely to become the academic leaders of the 21st century.
Regarding his research Hutson says, "The ultimate goal is to understand human development, but we can't study these processes in human embryos for both ethical and practical reasons. However, the basic processes appear to be analogous in higher organisms. So there is a tremendous amount we can learn from studying fruit flies.”
Hutson's basic tools are the laser and a special kind of microscope, called a confocal microscope, that is designed to work with fluorescent samples. His subjects are the eggs of special fruit flies (Drosophila) that have been genetically engineered to produce a green fluorescent protein originally extracted from a jellyfish. The glowing protein makes the cells show up clearly in the confocal microscope so he can measure their movements with very high precision.
During the first 24 hours of development, a Drosophila embryo undergoes several major transformations of its basic geometry: First, it forms into a hollow shell of cells known as the blastoderm. Then a furrow forms in the shell and forces some cells into the interior where they form an inner shell (a process called gastrulation). The cells around the exterior of the furrow subsequently develop into a distinct band, called the germ band. This band first extends until it reaches nearly all the way around the embryo's surface and then retracts back to its original size (processes called germ band extension and retraction). Finally, the thin layer of cells remaining on the opposite surface of the embryo are engulfed and replaced by epidermal (or skin) cells in a process known as dorsal closure. The result is a fly larva that is ready to crawl out of the egg in search of its first meal.
In a project that Hutson conducted as a post doctoral fellow at Duke University before coming to Vanderbilt in 2003, he studied the forces that drive one of these transformations: dorsal closure, a process closely related to wound closure. With the CAREER award funding, he will be building on the previous work to investigate the cellular and molecular mechanisms involved in germ band retraction.
The basic process that Hutson uses involves laser microsurgery. He has developed methods to make precise incisions in living fruit fly embryos as they develop. By making cuts in different orientations, at different stages of development and at different locations within an embryo, he can determine the direction and magnitude of the local tension pushing and pulling on the cells. In the simplest cases, a cut perpendicular to the direction of the local force gapes open, while a cut parallel to the direction remains closed.
Hutson also measures inter-cellular forces by using a laser to cut individual cell edges and using the confocal microscope to record the time-dependent recoil of surrounding cells. He uses computer models to solve the inverse problem of relating these recoils to the tension that existed in the cell edge before it was cut. These measurements will eventually allow him to construct a computer simulation of the interplay of forces that drive germ band retraction.