Bolger

Stress is a part of life, even on the cellular level. To survive and adapt to stresses such as nutrient deprivation or temperature shock, cells have to alter gene expression, especially protein translation, and alterations in these responses have been implicated in multiple human pathologies, including cancer and aging. Research in the Bolger lab focuses on understanding translation regulation during steady-state and stress conditions, and its impact on human disease, especially cancer. In particular, we are interested in how the dynamics of mRNA-protein complexes are controlled, focusing on a set of RNA helicase and RNP remodeling enzymes termed the DEAD-box proteins. DEAD-box proteins are required at virtually every step of gene expression to promote appropriate RNA-RNA and RNA-protein interactions, and several of them have been linked to cancer and other diseases. In particular, mutations in a DEAD-box protein, Ded1 in budding yeast and DDX3X in humans, have been strongly linked to medulloblastoma, the most common pediatric brain cancer. We are currently studying the role of Ded1/DDX3X in the translational response to cellular stress, as well as exploring the molecular defects in the cancer-associated mutations. We employ genetic, biochemical, and cell biology techniques, primarily (but not exclusively) utilizing budding yeast as a model organism. Uncovering these mechanisms and expanding this research to other studies of mRNP dynamics will both promote our basic understanding of the regulation of gene expression and elucidate the molecular pathways that influence cancer, aging, and other diseases. Please see the Bolger Lab website (bolgerlab.uga.edu) for more information.