Erik Jorgensen's enthusiasm for genetics nearly cost him his life. Celebrating the sequencing of the C. elegans genome in 1998, he scrambled to the top of a bookshelf to address his research team. The shelf collapsed and a bracket struck his chest, nearly piercing his heart. He spent weeks in a coma and emerged months later from the hospital. Now he jokes about wearing an inflatable suit around the lab as protection against his next fall.
Jorgensen's enthusiasm hasn't waned, and his brush with death didn't prevent him from setting new standards for rigorous study of the communications networks of the nervous system. Using the humble worm whose recently sequenced genome he recognized as an incredibly powerful research tool, Jorgensen is reconstructing what he calls the nanomachine of the synapse—the junction between two neurons. By defining the molecular components required for neurotransmission, he hopes both to develop drugs to treat defects in the process and to understand how the synapse holds the key to memory.
Most communication within the nervous system occurs when neurons fire off messages to each other at these junctions. When an impulse is generated in the neuron, vesicles packed with neurotransmitters travel to the synaptic membrane, where the vesicle and membrane fuse, releasing the vesicle's contents into the synapse. The neurotransmitters then move across the synaptic cleft to bind to receptors on the adjacent cell. At any given time, millions of neurons are communicating with each other across their synapses.
Jorgensen and his team have found more than 30 genes involved in normal synaptic function. To aid in the search, he devised a method of measuring the strength of the C. elegans neuromuscular junction, and is using this technology to measure how that strength changes with mutations in various genes. C. elegans is well suited to these studies because it can be kept alive even in the absence of a functioning nervous system. It is impossible to test the function of synapse proteins in most organisms, because, as Jorgensen says, most organisms that have defects in their synapses are dead.
