Elizabeth Villa, Ph.D.

Research

My lab is working to develop the tools needed to view the precise conformation of chromosomes as they are packaged inside the nucleus of a living cell. Deep within the cell, DNA molecules are wrapped around nuclear proteins and folded into structures that unfurl and recondense as the cell turns the underlying genes on and off. As a postdoctoral fellow, I developed a method for “micromachining” living cells to produce windows through which this dynamic nuclear architecture can be microscopically viewed in unprecedented detail. Now, combining this technique with advanced methods in molecular and computational biology and cryo-electron tomography, I will develop a set of “tags” that can be attached to proteins of interest, allowing me to visualize—at a three-dimensional, near-atomic level—the basic principles behind how we store and read our genetic information. These findings could eventually lead to the development of new methods to control gene activation—an ability that has potential therapeutic applications across a broad range of human disease.

As an Innovation Fund investigator, Elizabeth Villa, Ph.D., is teaming up with Kimberly Cooper, Ph.D., to resolve how chondrocytes function during bone growth. In mammals, chondrocytes—specialized cells that reside at the ends of bones—swell massively and secrete large proteins that become the scaffold for building bone. This process is the primary contributor to bone elongation. How chondrocytes maintain their function in a swollen state, however, is a mystery, given that fluctuations in cell volume typically trigger protective and adaptive responses. To address this question, the pair will use cryo-electron tomography to examine chondrocytes at a sub-nanometer scale. The project unites two previously unconnected fields of study: Cooper’s extensive experience in skeletal biology and Villa’s expertise in structural cell biology. Together, the researchers will test the hypotheses raised by their preliminary data indicating that the large-scale production of small vesicles drives chondrocyte swelling and protein secretion. This work could elucidate cell functions that are fundamental to the growth of all mammals.