Dr. Shiva Singh
Molecular Genetics of Complex Diseases and Phenotype
FETAL ALCOHOL SYNDROME PROJECT
Alcohol consumption during pregnancy is one of the most common early events known to affect development, and can cause severe physical and neurobehavioural abnormalities that characterize fetal alcohol effects (FAE) and fetal alcohol syndrome (FAS). This project seeks to elucidate the mechanisms through which alcohol acts on the developing brain by examining gene expression changes that occur in response to alcohol exposure at critical developmental stages. We hypothesize that FAS abnormalities are caused by the direct effect of alcohol on differentiating brain cells that are highly sensitive to events causing cellular stress. This results in apoptosis and distorted gene expression. C57BL/6J inbred mouse strain has been established as the standard animal model of FAS. The numerous genetic and phenotypic resources available for this strain makes it an ideal for genetic manipulation and analysis, and it differs with other strains (DBA/2J mice are of particular interest) for a number of alcohol-related phenotypes. These mice also exhibit similar patterns of physiological abnormalities following developmental alcohol exposure as humans.
Our reseach has used microarrays to identify ethanol-respsonsive, strain-specific, and strain-specifically ethanol-responsive genes. A large proportion of those genes identified have roles in cell stress response, apoptosis, and cell cyle control. The experimental objective of this project is to identify genes, biochemical pathways and systems that are critical in alcohol-specific pathophysiology during neurodevelopment, using mice as the model system. We examine the expression and regulation of relevant genes by a variety of bioinformatic and lab-based approaches, with focus on gene interactions and co-regulation, with the goal of elucidating the most logical pathways affected by alcohol. The results will have the potential to lead to the development of treatments that may protect the developing fetus from exposure to alcohol and other insults.