Core Research Projects
One of the most exciting scientific breakthroughs to impact cancer research has been the discovery of the importance of the chromatin structure and the central role of epigenomic modifications in gene expression. A fundamental and long-standing question in cancer research is what happens at the genomic level to change a typical cell from a normal phenotype into a malignant one. The linkage between some types of cancer and gene mutations is apparent, but that phenomenon is not observed in every class of tumor cell. How, then is gene expression so radically altered in tumor cells? The answer may be found by analyzing how biological and environmental factors alter chromosome mechanics and chromatin organization in the nucleus in a way that ultimately lead to the aberrant transcription seen in cancer cells.
CR-PSOC project teams will test the hypothesis that chromatin structure and nuclear organization is critically deranged in in the earliest stages cancer. A series of physical science approaches will examine whether changes in chromatin folding result in aberrant patterns of gene expression that drive cancer progression.
The Center consists of three interrelated project areas, each focused on different aspects of chromatin structure and function. Each project integrates emerging physical science approaches and molecular and cancer cell biology tools, as well as theory and modeling methods from the physical sciences, to achieve a quantitative and predictive understanding of the of deregulation of chromatin mechanics, epigenetic regulatory pathways, gene expression, and the nuclear environment in cancer.
In-depth examination of the physical features of a large molecular assembly such as chromatin, and analysis of the nature of ionic environments in nuclei, have proven difficult because of a lack of ultrasensitive analytical and high resolution imaging capabilities needed to work at these length scales. The CR-PSOC resolves these difficulties by bringing together a unique constellation of physical science, chemical biology, and genetics expertise and couples this expertise with cutting edge analytical instrumentation, specialized sequencing technology, super high resolution imaging modalities, and novel cancer model systems. This combination of expertise and resources enables Center investigators and members of the Physical Sciences Oncology Network to examine the structural and functional aspects of chromatin and nuclear dynamics in cancer at unprecedented depth and breadth.
Center investigators use state-of-the-art technologies to understand how molecular and physiochemical changes in the chromatin micro-environment affect the physical characteristics of chromatin; including elasticity, force, and light scattering. They interrogate a number of key model systems in cancer biology and determine what physical and chemical changes occur in chromatin packaging during the induction of pluripotency in the stem cell and the cancer cell. The extensive translational resources of Northwestern’s Chemistry of Life Processes Institute supports the efforts of Center investigators to identify potential targets for therapeutic intervention and develop new or repurpose existing therapeutics.