Jay D. Gralla
Jay D. Gralla
Boyer Hall 436
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.
DNA Biochemistry and Gene Regulation
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.
Harvard University Jane Coffin Childs Fellow in Molecular Biology
Pasteur Institute, France EMBO Fellow in Biochemical Oncology
UCLA Seaborg Award
Tran Khiem, Gralla Jay D The TFIIB tip domain couples transcription initiation to events involved in RNA processing J Biol Chem. 2010 Dec 17;285(51):39580-7.
Gralla Jay D, Huo Yi-Xin Remodeling and activation of Escherichia coli RNA polymerase by osmolytes. Biochemistry. 2008 Dec 16;47(50):13189-96.
Gralla Jay D, Huo Yi-Xin Remodeling and activation of Escherichia coli RNA polymerase by osmolytes. Biochemistry, 2008; 47(50): 13189-96.
Huo Yi-Xin, Rosenthal Adam Z, Gralla Jay D General stress response signalling: unwrapping transcription complexes by DNA relaxation via the sigma38 C-terminal domain. Molecular microbiology, 2008; 70(2): 369-78.
Tran Khiem, Gralla Jay D Control of the timing of promoter escape and RNA catalysis by the transcription factor IIb fingertip. The Journal of biological chemistry, 2008; 283(23): 15665-71.
Rosenthal Adam Z, Kim Youngbae, Gralla Jay D Regulation of transcription by acetate in Escherichia coli: in vivo and in vitro comparisons. Mol. Microbiol., 2008; 68(4): 907-17.
Rosenthal Adam Z, Kim Youngbae, Gralla Jay D Poising of Escherichia coli RNA polymerase and its release from the sigma 38 C-terminal tail for osmY transcription. J. Mol. Biol., 2008; 376(4): 938-49.
Kim Youngbae, Lew Chih M, Gralla Jay D Escherichia coli pfs transcription: regulation and proposed roles in autoinducer-2 synthesis and purine excretion. J. Bacteriol., 2006; 188(21): 7457-63.
Gralla Jay D, Vargas David R Potassium glutamate as a transcriptional inhibitor during bacterial osmoregulation. EMBO J., 2006; 25(7): 1515-21.
Rosenthal Adam Z, Hu Minshan, Gralla Jay D Osmolyte-induced transcription: -35 region elements and recognition by sigma38 (rpoS). Mol. Microbiol., 2006; 59(3): 1052-61.
Lin Yin C, Gralla Jay D Stimulation of the XPB ATP-dependent helicase by the beta subunit of TFIIE. Nucleic Acids Res., 2005; 33(9): 3072-81.
Lin Yin Chun, Choi Wai S, Gralla Jay D TFIIH XPB mutants suggest a unified bacterial-like mechanism for promoter opening but not escape. Nat. Struct. Mol. Biol., 2005; 12(7): 603-7.
Gralla Jay D Escherichia coli ribosomal RNA transcription: regulatory roles for ppGpp, NTPs, architectural proteins and a polymerase-binding protein. Mol. Microbiol., 2005; 55(4): 973-7.
Lew Chih M, Gralla Jay D Nucleotide-dependent isomerization of Escherichia coli RNA polymerase. Biochemistry, 2004; 43(39): 12660-6.
Choi Wai S, Lin Yin C, Gralla Jay D The Schizosaccharomyces pombe open promoter bubble: mammalian-like arrangement and properties. J. Mol. Biol., 2004; 340(5): 981-9.
Lew Chih M, Gralla Jay D Mechanism of stimulation of ribosomal promoters by binding of the +1 and +2 nucleotides. J. Biol. Chem., 2004; 279(19): 19481-5.
Lee Shun Jin, Gralla Jay D Osmo-regulation of bacterial transcription via poised RNA polymerase. Mol. Cell, 2004; 14(2): 153-62.