“We are delighted to honor Lily and Yuh-Nung Jan with this prize,” said Robert Desimone, director of the McGovern Institute and chair of the selection committee. “They have made major contributions to many areas of neuroscience, and their work exemplifies the power of research on model organisms to answer fundamental questions about the brain. In previous years, we have awarded the prize to a single individual, but that would have been impossible in this case; as a husband-and-wife team, the Jans have been collaborators for over 30 years, and their contributions cannot be separated.”
Their first significant discovery, made when they were postdocs in the laboratory of Stephen Kuffler, was to prove the existence of peptide neurotransmitters. Short secreted peptides were known to function as hormones, circulating throughout the bloodstream and affecting multiple target organs, but the Jans provided the first definitive evidence that a peptide known as LHRH could also be released by nerve terminals in response to neural activity and could regulate the electrical activity of other nearby neurons. This was an important early discovery in what has now become a major field of study; there are now dozens of peptide neurotransmitters known, the subjects of thousands of papers and important targets for drug discovery.
The Jans have been pioneers in the study of potassium channels, which are central to understanding the brain’s electrical properties. These channels, which are found in all organisms including humans, are responsible for terminating electrical activity in neurons. When the Jans began to study them, potassium channels could only be detected indirectly through their electrical effects; efforts to purify these channels biochemically had not been successful and their molecular identity was unknown.
The Jans instead adopted a genetic approach; they studied a mutant strain of fruit flies known as ‘Shaker’ because of their abnormal limb movements, and provided evidence that this abnormality was due to a defective potassium channel. Following a decade-long effort, in 1987 they published a landmark paper reporting the cloning of the shaker gene (a simple task today but a major undertaking at that time) and establishing that it encoded a potassium channel. This discovery opened the floodgates to an entire field of research; potassium channels are now recognized to be the most numerous and diverse class of ion channels in the brain, and over the past 20 years the Jans have continued to contribute many important advances to our understanding of their function.
Genetic research on fruit flies has also been critical to our understanding of embryonic development, and the Jans are also leaders in the field of developmental neuroscience. Their work has helped explain many aspects of brain development, including the process by which undifferentiated cells of the developing embryo become committed to form the nervous system; how a single dividing cell can give rise to two dissimilar daughter cells, thus allowing the generation of an extraordinary diversity of mature neuronal types; and how these neurons develop their distinctive shapes and specializations such as elaborate dendritic arbors, giving rise to the intricate wiring patterns on which the function of the nervous system is based.
The McGovern Institute will award the Scolnick Prize to Drs. Jan and Jan on Friday, May 28, 2010. At 4 p.m. they will deliver a joint lecture entitled "Dendrite morphogenesis and channel regulation: implications for mental health and neurological disorders,” to be followed by a reception, at the McGovern Institute in the Brain and Cognitive Sciences Complex, 43 Vassar St. (building 46, room 3002) in Cambridge. The event is free and open to the public.