Research Interest:

The ability of a cell to function normally and carry out its specialized functions depends critically on the proper regulation and expression of its genes. This regulation has its roots in the diversity and specificity of interactions between biological macromolecules. At the level of control of transcription this means primarily the interactions between promoter DNA sequences and proteins and the interactions of proteins with each other. We study how these interactions occur and what they do to control the process of gene transcription. We also study what is wrong with these interactions when mutations cause defects in transcription and how certain effectors might influence the expression of the mutant and normal genes.

The approach used relies on comparing transcriptional control in reconstructed systems with that occurring inside cells. We have developed chemistry-based procedures for probing the interactions of proteins with DNA. These are applied to mammalian, yeast and bacterial cells and extracts under conditions where the activity of genes may be controlled by biological means. The results lead to models for what types of nucleoprotein complexes assemble when genes are active and how this changes when they are inactivated by mutation or by biological repression. These models are tested by isolating the regulatory macromolecules from cells and reconstructing the system in vitro. In some cases the isolated proteins are then mutated to learn the roles of specific protein domains in transcriptional regulation. The picture that is emerging promises to contribute significantly to our understanding of what goes wrong when cells specify inappropriate patterns of gene transcription and are converted to the transformed state.

Detailed Biography:

Dr. Jay Gralla is a DNA biochemist with laboratories in the Molecular Biology Institute. His laboratory includes students from the Department of Chemistry and Biochemistry and the the Gene Regulation Program as well as post-doctoral fellows and support staff. Dr. Gralla is well known for basic studies that define the critical biochemical steps that are associated with transcription initiation. These studies are unique in integrating concepts across the biological kingdom from bacteria to yeast to man. He was trained initially at Yale and Harvard Universities and has been a visiting scientist at MIT and the Pasteur Institute.