I. Regulation of Centriole Duplication. Errors in chromosome segregation during cell division can result in the production of aneuploid daughter cells. This is particularly devastating during development, as aneuploidy is an underlying cause of miscarriage, birth defects, and cancers. During cell division, the accurate transmission of replicated chromosomes depends on the assembly of a bipolar spindle which is facilitated by the presence of centrioles, tiny organelles that help generate and organize spindle microtubules. Normally cells contain a single centriole pair, each duplicating only once prior to entering cell division. However, these mother centrioles have the capacity to assemble multiple daughters simultaneously. If cells assemble excess daughter centrioles (known as centriole amplification), then multipolar spindle assembly can ensue, leading to aneuploidy and increased risk for miscarriage/birth defects and cancer. In normal cells, what limits mother centrioles to assemble only a single daughter is unknown. It is known, however, that Polo-like kinase 4 (Plk4), the conserved master-initiator of centriole assembly, plays a key role in the duplication process. Therefore, a major goal of the Rogers lab is discovering how Plk4 works and how Plk4's activity is regulated.
II. Nuclear Organization During Interphase. A cell must organize its chromatin to accommodate the active transcription of genes and -- for those cells progressing through the cell cycle -- the replication of the cell's genome. One aspect of chromatin organization is its degree of compaction: while chromatin clearly undergoes extreme compaction during mitosis, the chromatin within interphase cells is also compacted but at a more moderate level. Importantly, interphase chromatin compaction is required for normal cellular function. In collaboration with Dr. Gio Bosco (Dartmouth), my lab is interested in understanding the regulation and physiological significance of interphase nuclear organization, particularly at the level of chromatin compaction.