OUR RESEARCH
In the IJL Lab, we are interested in understanding how the cells remodel their nuclear envelopes and the consequences of defective nuclear envelope remodeling.
Why do we study nuclear envelope remodeling?
The nuclear envelope (NE) is the double membrane bilayer that separates the chromatin from the rest of the cell in eukaryotes. The integrity of the NE is critical to the function and stability of the genome. Defects in the NE result in various diseases including myopathies and progeria, and are also frequently observed in cancers and ageing cells. Loss of NE integrity may also trigger innate immune response or allow for nuclear entry of the viral genome, critical for some viruses' reproduction.
To establish and maintain NE integrity, any remodeling of NE requires intricate orchestration. In the cell, NE remodeling could be part of a normal cellular process (e.g. biogenesis of the nuclear pore complex) or a response to external insults (e.g. after nuclear rupture resulted from excess mechanic force). NE remodeling at the right place and right time is crucial to the integrity of the NE.
How do we study nuclear envelope remodeling?
We utilize a unique fission yeast called Schizosaccharomyces japonicus (S. japonicus) to be a genetic model system for NE remodeling. Unlike other established yeast model systems, S. japonicus undergoes partial NE disassembly during mitosis and therefore requires NE reassembly and sealing afterwards. Taking advantage of this characteristics, we designed and performed a 3-tier genetic screen, followed by next-generation sequencing, to identify factors that can enhance NE integrity. We identified both gain-of-function mutants of proteins that promote NE assembly and loss-of-function mutants of proteins that impair with NE assembly in the absence of CHMP7, a key protein in NE sealing. Next, we will use genetics, biochemistry, and live-cell microscopy to further dissect molecular mechanisms required to establish and maintain NE integrity.
Current projects
Mechanisms for NE assembly after mitosis
Assembly of higher-order structures on the NE
Conservation of NE remodeling machinery