Grant: Discovery Grants Program - Individual

The chemical modification of DNA by methylation is thought to play an important role in controlling gene expression during the development of vertebrates.  Also, a number of human diseases and syndromes are recognized as being caused by, or associated with, alterations in the amount or pattern of DNA methylation.  Methylation is now thought to be playing an equally important role in vertebrate aging as well and changes in methylation during aging may be involved in producing the increased incidence of cancer as we get older.  Consequently, an understanding of DNA methylation and the methyltransferases (those enzymes that add the methylation to DNA) is important to our understanding of normal and abnormal development and aging in all vertebrates up to and including humans. The zebrafish provides an excellent model for the study of methylation at both the beginning and end of life because they are easy to keep, breed and manipulate.  At the same time they are similar enough to other vertebrates to make extrapolations possible .  We are, therefore, attempting to use this model system to more precisely define the role of the DNA methylation in development in order to understand how the developmental process is controlled.  We are also using this system to determine the role of methylation in aging in order to understand how aging in vertebrates occurs.   With a better understanding of the causes of aging we may be better able to minimize the debilitating effects of the process.