Grant: Discovery Grants Program - Individual

Every cell within a multicellular organism, such as a human, contains the same genetic blueprint - so what makes a blood cell different from a muscle cell? The answer is how the genetic material is activated. Different cell types activate different sets of genes to make proteins that are specific for the function of the particular cell. For example, a blood cell would produce a protein for carrying oxygen through the body, while a muscle cell would produce a protein that is used for cell contraction. The process of this differential gene activation is referred to as gene expression. The control of gene expression occurs at many levels within a cell but the most common level of control is at the initiation of transcription. Transcription is the mechanism that makes 'photocopies' of particular genes. These copies are called messenger RNA (mRNA), and they serve as the instructions for the production of proteins. The initiation of transcription is tightly controlled through the orderly assembly of specific factors that recognize and bind to specific DNA sequences in regions called promoters, which precede the beginning of each gene. I am interested in studying gene expression, in particular the regulation of transcription initiation in the single cell protozoan, Giardia lamblia. This organism is the most common cause of infectious diarrhea in humans worldwide, and is a frequent contaminant of freshwaters in Canada. Giardia is an eukaryote, like a human cell, because its genes are located in a special compartment within the cell called the nucleus. However, the regulatory regions for the control of transcription initiation in Giardia are smaller and less complex than those in a human cell, and the number of factors that are required to assemble at these regions before transcription can initiate appears to be greatly reduced in Giardia compared to a human cell. Therefore, the study of transcription and gene expression in Giardia would be an opportunity to identify the bare essentials of these processes in a streamlined biological system. Moreover, these studies may identify unique aspects of these pathways in Giardia that can be exploited to develop improved and more effective treatments of Giardia infections.