The Biogenesis and Function of Intracellular Organelles
Differentiated cells all have different internal structures that allow them to carry out their specialized tasks in our bodies. How are these structures built? How do proteins know where to go so that they end up in the correct compartment? How does a living cell adjust the amount of organelles according to need? For the most part, the answers to these questions are unknown. Recently, we have made great progress in deciphering intracellular signaling pathways that allow organelles to affect the gene expression programs in the cell nucleus. The pathways studied have revealed fascinating new ways of propagating signals. One example is the pathway by which the abundance of the endoplasmic reticulum is regulated by the "unfolded protein response" (UPR), which utilizes an mRNA-splicing step that bypasses all of the machinery commonly involved in mRNA splicing. A student will explore mechanistic and physiological aspects of these signaling pathways. The goal is to learn how individual proteins function as molecular switches and how these switches are connected to one another in signaling networks that regulate organelle function and abundance. A combination of genetic, molecular engineering, microscopic, and biochemical techniques will be applied in both mammalian and yeast systems, with increasing emphasis on cancer biology. In particular, we are exploring whether pharmacological UPR modulation can be of therapeutic value in multiple myeloma, a cancer of cells of the immune system. Results obtained in evolutionarily distant cells will be compared to distinguish fundamental aspects of regulation common to all eukaryotic cells from species-specific variations. See our lab page for more details.