Purdue University

It is becoming increasingly clear that genetic mutations alone cannot fully account for devastating chronic adult-onset diseases, neurological disorders and cancer.  Rather, environmental assaults also contribute significantly to disease etiology and pathology.  Environmental factors act on epigenetic processes in a cell to alter gene expression without causing a genetic mutation.  This gives the cell plasticity to respond to the environment without causing permanent damage to its DNA.  Understanding how epigenetic marks govern gene expression at the single cell level will foster development of intervention strategies to change cell fate by inducing or reversing epigenetic modifications.  However, current knowledge of how these marks function is limited by existing technologies.  To break through this critical limitation, the research group will create, refine and validate a set of technologies that will enable researchers to identify, examine and even alter epigenetic marks in a locus-specific manner at the single cell level.  They will test this system in a neural stem cell differentiation model and validate it in a 3D breast epithelial tissue culture system.  This toolkit will be designed to enable users to customize strategies to identify and alter epigenetic processes at a single gene in individual cells to reset key events during neural differentiation or tumor formation.