Top image

EMBL/EMBO Joint Conference 2004

Mario Capecchi, University of Utah, USA

Biography

Mario R. Capecchi was born in Verona, Italy, in 1937. He received his B.S. in chemistry and physics from Antioch College in 1961 and his Ph.D. in biophysics from Harvard University in 1967. He completed his thesis work under the guidance of Dr. James D. Watson. From 1967-69 he was a Junior Fellow of the Society of Fellows at Harvard University. In 1969, he became an Assistant Professor in the Department of Biochemistry, Harvard School of Medicine, and was promoted to Associate Professor in 1971. In 1973, he joined the faculty at the University of Utah as a Professor of Biology. Since 1988, Dr. Capecchi has been an investigator at the Howard Hughes Medical Institute; since 1989, a Professor of Human Genetics at the University of Utah School of Medicine; and since 1993, Distinguished Professor of Human Genetics and Biology. He is also co-chairman of the Department of Human Genetics. Dr. Capecchi is best known for pioneering the technology of gene targeting in mouse embryo-derived stem cells that allows scientists to create mice with mutations in any desired gene by choosing which gene to mutate and how to mutate it. This gives the investigator virtually complete freedom in manipulating the DNA sequences in the genome of living mice, and allows detailed evaluation of any geneës function during its development or post-developmental phase. Research interests include the molecular genetic analysis of early mouse development, neural development in mammals, production of murine models of human genetic diseases, cancer and factors affecting life expectancy, homologous recombination and programmed genomic rearrangements in the mouse. Dr. Capecchi is a member of the National Academy of Sciences (1991) and the European Academy of Sciences (2002). His prestigious awards include the Bristol-Myers Squibb Award (1992), Gairdner Foundation International Award (1993), General Motors Corporation's Alfred P. Sloan Jr. Prize (1994), German Molecular Bioanalytics Prize (1996), Kyoto Prize in Basic Sciences (1996), Baxter Award for Distinguished Research in the Biomedical Sciences (1998), Colby Presidential Endowed Chair (1999), Italian Premio Phoenix-Anni Verdi Award (2000), Spanish Jimínez-Diáz Prize (2001), Albert Lasker Award (2001), National Medal of Science (2001), John Scott Medal Award (2002), Massry Prize (2002), Pezcoller Foundation-AACR International Award for Cancer Research (2003) and Wolf Prize in Medicine (2002/03).

Abstract

Use of the mouse to study human longevity

Gene targeting provides the means for creating strains of mice with designed alteration in any chosen genetic locus. This technology permits the evaluation of the functions of genes in the intact mammal and the systematic dissection of the most complex biological processes from embryogenesis to aging. With virtually complete control over how a gene's DNA sequence is modified, the investigator can disrupt the gene in the germline, and as a consequence, every cell of the mouse carries the disrupted gene, or the modification can be implemented conditionally, thereby restricting the function of the gene in chosen tissues and/or temporal periods of the animal, including adulthood. Of all of the model organisms, the mouse's genome and physiology is most similar to ours, so it would appear that this creature is likely to be the most informative experimental organism to evaluate the multiple facets that affect the process of aging and permit evaluation of the genetic and environmental factors that most significantly alter the aging process. Is it reasonable to anticipate that the lifespan of the laboratory mouse can be significantly changed through genetic manipulations? Comparisons among the life spans of different mammalian species of comparable size and physiology suggest that it should be. For example, the average life span of the laboratory mouse is approximately two years. However, the microbat species Myotis lucifugus readily attains a life expectancy of thirty years. These two species are nearly identical in size and have very similar physiological parameters such as heart rates, blood pressure, body temperatures and metabolic rates. It is not unreasonable to assume that such enormous differences in life expectancies between these two species is determined in part by genetic differences. We will explore technologies that use the mouse as a surrogate and may allow the identification of such genetic determinants.