How is the brain wired to produce behaviors critical for life? This is one of the central scientific questions being addressed at the Janelia Farm campus of the Howard Hughes Medical Institute (HHMI). The HHMI scientists are making amazing progress at Janelia Farm, working in multidiscplinary teams are using both bottom-up and top-down approaches, in a new state-of-the-art $500M facility.
The ultimate aim, of course, is to understand behaviors of the human brain, but the sheer complexity of our brain makes this a daunting challenge. Instead, the HHMI scientists are studying organisms, such as fruit flies and C. elegans (a type of microscopic worm), with relatively simpler nervous systems. Since evolution tends to conserve form and function across species, lessons learned by studying the brains and behaviors of these animals can be used to understand that of humans.
Broadly speaking, the problem is being attacked from two directions. In the bottom-up approach, Drs. Scheffer, Chklovskii, and others are trying to map the fly and worm brains in very high detail. With the wiring diagram of brain in hand, these scientists can ask what behaviors the neural circuitry can produce and regulate, or test existing theories about the relationship between brain structure and function. In the top-down approach, Drs. Leonardo, Reiser, Branson, and others are quantifying animal behavior, such as the ability to sense the direction of gravity, detect motion, or to track and catch prey. By comparing normal animals versus animals with targeted brain alterations, these scientists can identify and further analyze the circuitry underlying the behavior of interest.
Neurobiology is one of the great scientific frontiers, in part because we lack the sophisticated tools to address even the simplest of questions about the brain. So, I was really blown away to hear about the scale of available resources and type of technology being invented at HHMI to enable the research. For example, the brain maps are created using several (!) electron microscopes customized on-site for high throughput imaging of thin sections of brain. The resulting stack of images are used to create a 3D reconstruction of the individual neurons and their connections.
In another example, in order to study how dragonflies are able to capture smaller flies in mid-air, Dr. Leonardo and his team spent two years building and optimizing a controlled experimental room that simulates the natural world (complete with forest and wildflower wallpaper). This room is equipped with high speed, high resolution cameras to image, and triangulate in 3D, the position of the dragonfly and orientation of the individual wings. Even more mind boggling, the dragonflies are wired to a tiny microchip so that the activity of individual neurons can also be recorded in mid-flight!
Not surprisingly, developing and using such advanced technology requires a really special environment that HHMI has carefully fostered. Engineers, computer scientists, and mathematicians work in tight collaboration with the neuroscientists to advance the state of the art and enable experiments that were not previously possible. They are actively recruiting creative and motivated minds with any of these professional backgrounds. Also, everything about the cloistered, soothing environment of Janelia Farm is designed to encourage thinking across the traditional disciplines, and the facility tour left no doubt that HHMI scientists are more than adequately equipped with the resources to rapidly pursue the creative ideas that emerge.
One a personal note, as a new Siebel Scholar, it was great to finally meet other Siebel Scholars in person, especially those in the area and those with interests in biology and medicine who flew in from various locations. Thanks also to Nitsa and Karen for coming (it was great to catch up) and to them, Jenny, Tom and everyone else who made this fantastic event possible!