The cell controls its diverse metabolic functions by compartmentalization. For example, DNA is sequestered in the nucleus, separated from the rest of the cell by a membrane barrier termed the nuclear envelope. Likewise, mitochondria are energy producing organelles and the endoplasmic reticulum serves as a transit station for proteins destined to leave the cell. This physical separation of function within the cell provides it with the ability to control processes independently, but demands a highly ordered and efficient transit system to ensure correct protein sorting and organelle assembly. Defects in these transit systems alter the ability of cells to direct proteins to their correct compartments, or to control their gene expression, and can have catastrophic consequences to human health. The Aitchison laboratory seeks to understand how this three-dimensional cellular architecture is maintained and how it imparts control over biological processes.
Research
Using yeast cells as research models, the Aitchison lab focuses on applying systems approaches to two fundamental problems in cell biology.
In the first area, of nucleocytoplasmic exchange, the lab studies how proteins selectively gain access to the DNA in the nucleus. Transport factors, termed karyopherins shepherd cargoes through nuclear pores spread over the surface of the cell nucleus. The pores are occupied by large elaborate protein complexes termed nuclear pore complexes. The Aitchison laboratory examines how nuclear pore complexes govern traffic between the nucleus and cytoplasm and how karyopherins, and their respective cargoes selectively transit the pores. As this process is inextricably linked to regulated gene expression, the Aitchison group also studies how this transit system influences the functioning and development of cells.
The Aitchison laboratory also studies peroxisomes: essential cellular organelles that play diverse metabolic roles. Here, the goal is to understand how external signals trigger the development of peroxisomes and how the cell machinery builds and maintains the organelle. The comprehensive understanding of this dynamic process holds promise to provide insight into the biology of peroxisome biogenesis and into the human disease processes linked to peroxisome dysfunction.
In both of these areas, the Aitchison group is applying and developing new technologies in high throughput biology, functional genomics, proteomics, genetics, and computational biology. The group is devoted to merging these systems biology approaches with more traditional cell biological approaches to obtain new fundamental insights into cell biology.
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