Learning from worms
H. Robert Horvitz has devoted much of his career to studying the nematode worm Caenorhabditis elegans. Only 1 mm long and containing fewer than 1000 cells, C. elegans has proved to be remarkably informative for studying many biological problems, including the genetic control of development and behavior and the mechanisms that underlie neurodegenerative disease.
A simple nervous system
Horvitz's work has influenced many areas of biology over the years, but neuroscience has always been a central interest. By hunting for genetic mutations that affect C. elegans behaviors, Horvitz has revealed much about the genetic control of brain function, including how neural circuits control specific behaviors and how behavior is modulated by environment and experience. Many of the chemical signals used by the worm's nervous system are also present in the human brain. For example, Horvitz showed that serotonin, a neurotransmitter implicated in the control of human mood and appetite, also regulates the movement of worms. This finding has led to several new genes that affect serotonin signaling, which could help to identify potential targets for human drug development.
Another major theme of Horvitz's work is cell death. Apoptosis, or cell death, is a central feature of human neurodegenerative disease. Horvitz has shown that cell death is often an active process, and that many of the genes that control the deaths of worm neurons have counterparts in the human brain. Understanding how these genes operate has provided new insights into normal brain development as well as the pathological processes involved in many brain disorders. His discoveries might lead to new treatments for certain retinal degenerative diseases as well as for Alzheimer's, Parkinson's and Huntington's diseases, stroke and traumatic brain injury. Horvitz has recently begun to study the genetic basis of aging, and one of his aims is to understand how aging drives the degenerative process in conditions such as Alzheimer's disease.
In October 2002, the Nobel Prize in Physiology or Medicine was awarded to Horvitz, Sydney Brenner, and John El Sulston "for their discoveries concerning genetic regulation of organ development and programmed cell death." Watch Horvitz's Nobel lecture below.
Searching for human disease genes
In addition to his work on C. elegans, Horvitz also has a longstanding interest in human neurodegenerative disease. He was a principal member of the team that in 1993 identified the first gene to cause familial ALS (Lou Gehrig's disease), and in collaboration with colleagues at Massachusetts General Hospital he continues to work on the search for additional ALS genes.
H. Robert Horvitz, a founding member of the McGovern Institute, is the David Koch Professor in the Department of Biology, and an investigator at the Howard Hughes Medical Institute. Horvitz received his Ph.D. from Harvard University in 1974 and has been a faculty member at MIT's Department of Biology since 1978. He is a member of the National Academy of Sciences, and in 2002 he shared the Nobel Prize in Physiology or Medicine for discovering and characterizing the genes controlling cell death in the nematode worm Caenorhabditis elegans. He is a Fellow of the American Academy of Arts and Sciences, and a recipient of the Gairdner Foundation International Award, the Alfred P. Sloan, Jr. Prize from the General Motors Cancer Research Foundation, and the Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience. In 2005, he was awarded the James R. Killian Faculty Achievement Award which recognizes extraordinary professional accomplishment by full-time members of the MIT faculty.
Image: Kent Dayton