Nucleus – ER link
Nucleus – ER link
The disassembly and assembly of the nuclear membrane during mitosis is intimately choreographed by the separation of the nuclear and ER membrane. Differences in the cellular environment and cell-specific roles within an organism create diverse demands on the ER, an organelle that plays crucial roles in protein and lipid synthesis. When demands on the ER exceed its capacity, collectively referred to as ER stress, signaling ensues to promote adaptive pathways. Communication between the ER and nucleus occurs via the unfolded protein response (UPR), which leads to new transcriptional programs (see Research Area: UPR section). This is clearly vital, but is only part of the picture. In collaboration with Dr. Katie Ullman’s lab, we will broaden our investigation into the communication between the ER and the nucleus to include probing the crosstalk that takes place at the level of organelle architecture adaptations and, in turn, function. We will use a range of strategies to determine how the ER responds to specific changes in the nuclear architecture. These studies will provide a framework for understanding human diseases in which the ER must adapt to heightened demands for protein production, protein folding, and/or lipogenesis, as well as those in which malformations of the nucleus are prevalent, such as cancer.
This project is funded by the Paul Allen Frontiers Group.