The compartmentalization of genetic information within the nucleus of eukaryotes promoted the evolution of diverse mechanisms for regulating gene expression and genome stability. Simultaneously, cellular machineries arose to control molecular communication between the cytoplasm and nucleus. The department is actively engaged in examining these diverse mechanisms at both the molecular and organismal level. The ultimate goal is to provide a molecular context for how the cell integrates external and internal inputs to alter the genetic program during development, differentiation and disease.
The department uses a number of genetic model systems including yeasts, Trypanosomes, Drosophila and mice to investigate control of gene expression including the broad roles of RNA within the cell. One focus is geared towards understanding how RNA is folded, and how aberrant RNAs can be recognized and degraded. In addition, diverse gene regulatory mechanisms are being explored, including investigation into the RNAi pathway and the function of non-coding RNAs (such as piRNAs).
In both cases, epigenetic mechanisms within the nucleus and translational control in the cytoplasm contribute to the protein composition of the cell, playing key roles in such processes as stem cell self-renewal. The nucleus is defined by bounding membranes termed the nuclear envelope. In order for proteins and RNAs to cross this barrier, they must pass through massive protein channels called nuclear pore complexes. Interests in the department include understanding the biogenesis of nuclear pore complexes, the passage of nuclear envelope membrane proteins through these channels, and the connection of the nuclear envelope to the cytoskeleton.
In addition to trafficking of macromolecules, additional means of communication also exist between the cytoplasm and nucleus. Other areas of study include the transcriptional consequence of calcium signals arising from massive invaginations in the nuclear envelope and the ability of cytoskeletal forces to alter chromatin structure through complexes embedded in the nuclear envelope.