Center for 3D Structure and Physics of the Genome

We are very excited to be invited to participate in the 4D Nucleome Project organized by Dr. Job Dekker. In support of this project we will use our extensive knowledge and expertise in analyzing the nuclear phenotypes of cells derived from dermal biopsies of patients afflicted with Hutchinson-Gilford Progeria Syndrome (HGPS). We have been studying these cells since 2004 when it was discovered that the mutation causing the typical form of this premature aging disease resides in the nuclear lamin A gene. It should be noted that we have been studying the nuclear lamins since ~1984, when we reported that the lamin isoforms are members of the intermediate filament family of proteins. Our role in this project will be to determine the changes in nuclear architecture which take place as HGPS fibroblasts are “aged” in culture until they prematurely senesce. We will monitor the structural changes in HGPS cell nuclei using super-resolution microscopic techniques and coordinate these changes with the changes in chromatin organization analyzed by Dr. Dekker and other members of the project. These structural changes have been established in our laboratory. They will be analyzed using super-resolution microscopic techniques and at appropriate times in culture we will prepare them for analyses by other members of this project.