Eight noted investigators were recently awarded the prestigious Senator Jacob Javits Award in the Neurosciences, which provides for up to seven years of research funding from the National Institute of Neurological Disorders and Stroke (NINDS). A component of the National Institutes of Health, the NINDS is the nation's primary federal sponsor of research on the brain and nervous system.

Authorized by the United States Congress in 1983, the award honors the late U.S. Senator Jacob K. Javits, who was a strong advocate for research on a variety of neurological disorders. Senator Javits suffered from amyotrophic lateral sclerosis, the disabling neurodegenerative disease also known as Lou Gehrig's disease.

The award is presented to investigators who have demonstrated exceptional scientific excellence and productivity in research areas supported by the NINDS and who are expected to conduct cutting-edge research over the next 7 years. It provides guaranteed funding for 4 years, after which 3 additional years may be awarded pending receipt and approval of additional information. Investigators are nominated by NINDS staff, on the recommendation of the National Advisory Neurological Disorders and Stroke Council, from among a pool of competing grant applicants during a given grants cycle. An investigator may receive the Award only once, a policy that began in 1996.

Receiving the Senator Jacob Javits Award in the Neurosciences are:

Lynn W. Enquist, Ph.D., Professor and Chair of Molecular Biology, Princeton University. Dr. Enquist is using the pseudorabies virus (PRV) to identify nerve cell circuits in the intact rat nervous system. He is exploring the factors of PRV that allow it to penetrate and become lethal in the central nervous system, with the goal of identifying the PRV gene products that stimulate neuronal firing. PRV is a member of the herpes virus family and this work is expected to lead to a better understanding of the mechanisms of infection of neurons and the pain caused by these viruses. This work will also provide new insights into the nature of neuronal connections or synapses that lead into the brain and how they differ from neuronal synapses in other parts of the nervous system.

David L. Glanzman, Ph.D., Professor of Physiological Science and Neurobiology, University of California, Los Angeles. Using the marine snail Aplysia to study the cellular and molecular mechanisms of learning and memory, Dr. Glanzman has focused his research mainly on two simple forms of learning: classical conditioning and sensitization. His award will fund a series of innovative experiments that will combine behavioral, electrophysiological, pharmacological, and molecular techniques in investigating the roles of postsynaptic glutamate receptors in classical conditioning. The work will provide new insights into the mechanisms of neural plasticity.

Kristen M. Harris, Ph.D., Professor, Department of Neurobiology, Medical College of Georgia. A pioneer in the field of synaptic plasticity (the variability in the strength of a signal that is transmitted through a synapse), Dr. Harris has developed innovative approaches using a computer-assisted 3-dimensional reconstruction technique to quantitatively measure structural changes along the nerve cell's dendrites at central synapses during plasticity. Previous studies of long-term plasticity involved with in vitro preparations, such as brain slice, have limitations. The Javits Award will allow Dr. Harris to examine changes in synaptic structure and cellular mechanisms of learning and memory in the brains of awake, active animals. Her findings will help to identify synapses that are involved in cognitive processes, such as forming new memories, and may contribute to potential intervention strategies for cognitive dysfunction seen in degenerative neurological diseases.

Brian K. Kobilka, M.D., Professor of Molecular and Cellular Physiology and Medicine, Stanford University Brain Research Institute. Dr. Kobilka has developed sophisticated biochemical and biophysical technologies that have led to major advances in understanding cell-signaling mechanisms. He is a leader in G-protein coupled receptor (GPCR) structure and function, in which molecular structures on the surface of the cell bind to a protein and generate a signal. One of the largest and most important families of receptors in the human genome, GPCRs are involved in cellular responses to the majority of hormones and neurotransmitters and represent an enormously significant target for drug discovery. Dr. Kobilka's Javits Award will allow him to conduct further studies using adrenergic receptors (proteins involved in many neurologic disorders and with drug actions including antidepressants, antiepileptics, and antihistamines) as a model system to characterize GPCRs.

Alex L. Kolodkin, Ph.D., Professor of Neuroscience, Johns Hopkins University School of Medicine. Dr. Kolodkin is studying molecules that guide nerve cells into the brain and mechanisms that move a signal from outside to inside the cell. He is co-discoverer of the semaphorin family of guidance molecules and has identified the complex signaling they use to guide neurons to their correct targets during development. His work is unique in that it successfully combines fly and mouse genetic models to functionally study how axons, the cable-like appendages from nerve cells, reach their target sites. Research findings will further the understanding of how axons navigate, and should yield new insights into mechanisms of axonal regeneration after spinal cord injury, tumor development, and immune system function.

Jeffrey D. Macklis, M.D., Associate Professor of Neurology, Massachusetts General Hospital. Dr. Macklis has made significant contributions to the understanding of neuronal replacement and cellular repair of the brain following injury. His research shows that, contrary to previously held beliefs, the reconstruction of complex networks in the brain's cerebral cortex can be achieved in adulthood. Using a method that he pioneered, Dr. Macklis was the first investigator to demonstrate that, following localized injury, the adult mammalian precortex can be repopulated by new neurons. Some of these new nerve cells send axonal projections long distances into target regions and could potentially contribute to the restoration of function. In his most recent research proposal, Dr. Macklis hopes to identify the best conditions for the integration of neurons into existing networks of the somatosensory cortex, which receives tactile information from the body. His findings may lead to the development of cell replacement therapies to treat brain disorders.

Andrew P. McMahon, Ph.D., the Frank B. Baird, Jr., Professor of Molecular and Cellular Biology, Harvard University. A leader in the field of developmental biology and co-discoverer of the signaling protein named Sonic hedgehog (Shh), Dr. McMahon has made seminal contributions to the understanding of signal transduction pathways that control brain and spinal cord development. His research has established paradigms in the areas of embryonic pattern formation and axon guidance in the mouse and chick, providing a foundation for understanding and treating developmental neurological disorders and certain tumors. His Javits-winning research proposal — which combines embryonic manipulations possible in the chick with genetic methods available in the mouse — will advance our understanding of the development of the neural tube and spinal cord precursor cells, provide insight into Shh-linked tumors, and identify candidate molecular targets for therapeutic intervention for disorders that disturb patterning and cell proliferation.

Jerry Silver, Ph.D., Professor of Neurosciences, Case Western Reserve University School of Medicine. Dr. Silver investigates the role of astrocytes in spinal cord regeneration following injury. His work has established the inhibitory role astrocytes can play in preventing central nervous system (CNS) regeneration. These cells create a cellular and molecular barrier at the site of injury, called the glial scar. Dr. Silver has shown how certain potent axonal growth inhibitors (proteoglycans) contribute to that barrier to regeneration. Proteoglycans play a role in guiding or even blocking axonal growth during development, after injury, and in degenerative diseases. Dr. Silver has created a novel in vitro model of the glial scar, which combines growth-promoting and growth-inhibiting molecules involved in CNS white matter tract injury. His highly innovative research proposal will study the response of sensory and CNS neurons from adult and developing animals to this model system and test combination strategies to promote growth. Finally, he will test these strategies in vivo, attempting to stimulate sensory axons to grow past an inhibitory region at the dorsal root entry zone (the outer margin of the spinal cord). His findings may prove invaluable in developing and testing potential therapies for spinal cord injury.

The NINDS is a component of the NIH within the Department of Health and Human Services and is the nation's primary supporter of biomedical research on the brain and nervous system. More information about the NINDS and its research programs may be found at www.ninds.nih.gov. This release will be posted on the NINDS website at http://www.ninds.nih.gov/news and events/index.htm.