Martin Hetzer, Hearst Endowment associate professor in the Salk Institute's Molecular and Cell Biology Laboratory, has received a 2009 Senior Scholar Award in Aging from the Ellison Medical Foundation. He will receive $150,000 a year for four years to study the mechanisms at work in nuclear pore complexes, channels that mediate molecular traffic between the nucleus and cytoplasm of cells.
Changes in gene activity are part of the cellular aging process; however, the mechanisms that cause age-related alterations in gene expression are poorly understood. Hetzer has recently discovered that nuclear pore complexes, essential channels that shuttle molecules across the nuclear membrane, are extremely long-lived in non-dividing cells and deteriorate over time, causing cytoplasmic proteins to "leak" into the nucleus in neurons.
Because most of the cells in our bodies are non-dividing, he hypothesizes that this deterioration might be a general aging mechanism leading to agerelated defects in nuclear function, such as the loss of youthful gene expression programs. His lab has observed filaments of the cytoplasmic protein tubulin inside the nuclei of old mouse and rat neurons, for example, a phenomenon that has been linked to various neurological disorders, including Parkinson's disease. Based on this finding, he speculates that the deterioration of nuclear pore complexes over time might initiate or contribute to the onset of certain neurodegenerative diseases.
Hetzer will use the Ellison funding to investigate the molecular mechanisms that lead to the observed damage and loss of the proteins that make up the nuclear pore complexes. He also plans to study the physiological consequences of leaky nuclei for cell function and to analyze the consequences of defective nuclear pore complexes in gene expression.