Grant: Project Grant

Genetic material in our cells is sequestered within the cell nucleus. The access of various molecules to the DNA is tightly controlled by special molecular "biomachines" known as the Nuclear Pore Complexes. These Nuclear Pore Complexes shuttle millions of molecules in both directions and control which molecules get to pass through, and when. Nuclear Pore Complexes are central to a vast number of health and disease processes in the cell and in the organism. Their malfunction or disregulation is implicated in a large number of diseases - from viral infections to cancer and neurodegenerative disease. The unique internal architecture and composition of the Nuclear Pore Complexes makes it hard to directly study the mechanisms of their function. In the past several years, combinations of experimental investigations and multi-scale computational studies have emerged as powerful tools for the understanding of the organization and the function of this biological biomachine. The purpose of this proposal is to develop a comprehensive computational model of the Nuclear Pore Complex, and validate it with experimental measurements. The results of the study will serve as a stepping stone for future clinical applications for better understanding of disease mechanisms and development of better treatments for cancer, neurodegenerative diseases and other diseases.