James Nuñez, Ph.D.

Research

My lab will probe the mechanisms by which cells prevent transposable genetic elements from jumping around the genome. Half of the human genome is composed of parasitic fragments of DNA that have embedded themselves in our chromosomes. Many of these elements retain the capacity to move from one site to another, relocation that can disrupt gene activity. To suppress this movement, cells can chemically modify both DNA and its associated proteins in a way that keeps the chromosome tightly packaged. Recently, I discovered that the proteasome—a molecular machine that breaks down unwanted proteins—plays an unexpected role in this packaging. Now, using a suite of cutting-edge techniques in protein-DNA interaction mapping, super-resolution microscopy, and gene editing, I will assess whether proteasomes cluster preferentially on genes or sequences that are chemically modified, and determine what happens to embedded transposable elements when proteasome activity is incrementally eliminated. Because spontaneous relocation of transposable elements is associated with conditions such as neurodegenerative disease and cancer, my work could lead to novel therapeutics that act by keeping these genetic elements in their place.