"We want to reconstruct the elemental building plan of animals, tracking each cell from very early development until late stages, so that we know everything that has happened in terms of cell movement and cell division," Keller says. "In particular, we want to understand how the nervous system forms. Ultimately, we would like to collect the developmental history of every cell in the nervous system and link that information to the cell's final function. For this purpose, we need to be able to follow individual cells on a fairly large scale and over a long period of time."
It takes more than a week for the nervous system to become functional in an embryonic mouse. Even in the fruit fly, the process takes a day. Following development for that long means Keller's team must image tens of thousands of cells at thousands of time points, and that adds up to terabytes of data. "We can get good image data sets, but if we want to reconstruct them, this is something that we can't really do without help from the computer," Keller says.
Amat, a bioinformatics specialist on Keller's team, and his colleagues have solved that problem with the new computational method that identifies and tracks dividing cells as quickly as their high-speed microscope can capture images. The process is largely automated, but incorporates a manual editing step to improve accuracy for a small percentage of cells that are difficult to track computationally.
Keller's team has been grappling with how to interpret this kind of imaging data since 2010. The problem was challenging not only because of the sheer volume of data his light sheet microscope produced, but also because of the data's complexity. Cells in a developing embryo have different shapes and behaviors and can
|Contact: Jim Keeley|
Howard Hughes Medical Institute