Nutrition & Development Program
An affiliated initiative of the Clinical Nutrition Research Unit at Washington University
Director: Jonathan Gitlin, M.D., Helene B. Roberson Professor of Pediatrics
Jonathan Gitlin, M.D.
Congenital malformations are the leading cause of infant mortality in the United States. Despite recent advances identifying the molecular genetic basis of several human malformations, the genetic determinants of most structural birth defects remain unknown. Epidemiological studies as well as phenotype/genotype analyses now indicate that most birth defects arise from a complex interplay between genetics and nutrition. Moreover, there is clear evidence that suboptimal maternal nutrition is associated with many developmental defects; an elegant example is the association between impaired folate acquisition by the early embryo and incomplete neural tube development. The outcome of such studies has been the prevention of these defects by increased maternal folate intake.
The CNRU plans to enhance research evaluating the role of nutrition in development. Despite the considerable experimental and clinical data indicating a critical role for specific nutrients in early development, the mechanisms and timing of the key developmental events affected by nutrient deficiency are poorly understood. The zebrafish, Danio rerio, provides a powerful system to understand basic developmental processes because of the optical clarity of the developing embryo, its rapid external development and short generation time, the recent progress in zebrafish genetics and genomics, and the potential for forward genetic screens, transgenic models, specific gene disruptions and small-molecule screens. In fact, small molecule screens in zebrafish embryos have already been used to elucidate the logic and timing of vertebrate development, and have recently been used to identify drugs to reverse a model of complex congenital heart disease. The same approach can be used in nutrition to provide a greater understanding of the biological roles of specific nutrients in normal development and to identify where suboptimal nutrition can contribute to human birth defects. Moreover, these types of studies can also lead to the practical development of novel therapeutic approaches to prevent nutrition-related structural birth defects. This robust zebrafish model will provide novel insights into the role of nutrition in early vertebrate development and human disease.
Nutrition & Development is a priority area within the CNRU Pilot and Feasibility Program.
Copper
deficiency and development in humans and zebrafish
