David Brown, PhD

Professor Office: G223 Lab: G223 Office: (601) 984-1849 Email

I have a long-standing interest in the biology of chromatin. Early in my career I investigated core and linker histones in efforts to determine the functional significance of the pronounced heterogeneity of isotypes found in mammalian organisms. By manipulating the levels of individual linker histone isotypes, I was able to demonstrate that individual isotypes have distinct effects on gene expression and cell cycle progression.

In 2000, in collaboration with Tom Misteli, I was able to demonstrate that linker histones bind dynamically to chromatin, exhibiting a behavior in which a molecule of H1 is bound to a given nucleosome for about a minute before dissociating and moving to a new location. This was an extremely surprising observation and lead to a paradigm shift from the previous view that most chromatin was assembled into a static structure. Subsequent studies from my lab and others have confirmed that the dynamic binding of chromatin components is integral to many cellular processes including transcription, development, and the establishment and maintenance of pluripotency in stem cells.

I have since developed expertise in confocal microscopy-based techniques such as Fluorescence Recovery After Photobleaching (FRAP) to address multiple aspects of linker histone structure and function. In the current application, I propose to utilize these techniques and my expertise in chromatin biology to determine the role of linker histone-mediated changes in chromatin conformation on the response of mammalian cells to repair DNA damage.