Laboratory of David Burgess: Description
Research in the laboratory is in a sub-area of cell biology. Specifically, we are interested in how cells change shape or form and how that is precisely regulated using the cytoskeleton. Molecular motors using cytoskeletal tracks are required for such intracellular movements as cytokinesis, endocytosis, exocytosis, axonal transport and organellar movement in general. Although motors are required, many relatively basic questions are unanswered. Work in the laboratory focuses on two of these systems. A critically important cell shape change under investigation cytokinesis, the division of the cytoplasm during mitosis that is mediated by an actin-myosin based contractile ring in the cleavage furrow. One of the outstanding questions in the study of cell division is how timing and placement of the contractile ring is coupled to mitotic controls. Using micromanipulation, reverse genetics, as well as biochemical approaches in dividing echinoderm eggs, we have sought to determine how the timing of cytokinesis is coupled to the mitotic cycle. These experiments suggest that the timing of cytokinesis is a function of the delivery of a positive cleavage stimulus to the cortical cytoskeleton. Studies are underway to determine the nature of the cleavage stimulus and the response system orchestrating the assembly and dynamics of the contractile ring.
Another central question in cell biology is how the cytoskeleton is polarized in many cells resulting in such structures as the apical brush border microvilli of epithelial cells. The enterocyte serves as a model polarized epithelial cell because of its stereotypical actin and microtubule cytoskeleton and due to its targeted trafficking of Golgi–derived membranes. We studied the assembly of the brush border and microvilli cytoskeleton for many years. In recent years we have studied the targeted movement of membrane organelles in this cell. Proper delivery of sorted membrane proteins is essential to the normal absorptive functions of the intestinal epithelium. Several congenital human diseases of the small intestine, including sucrase–isomaltase deficiency and microvillar atrophy, are likely the result of improper Golgi sorting or delivery. We have used cell fractionation, biochemistry, high-resolution video-enhanced microscopy and electron microscopy to study the roles and regulation of molecular motors on Golgi-derived membranes. The work has involved study of both microtubule- and actin-based motors. It is anticipated that these studies will lead to results applicable to all cell types and will aid in the understanding of specific human diseases.
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