Jay D. Gralla, Ph.D.

Laboratory Address:
Paul Boyer Hall 422

Work Address:
Paul Boyer Hall 440

Lab Director, Gralla Lab
Professor, Chemistry and Biochemistry, Biochemistry, Molecular Biology
Administrator, Chemistry and Biochemistry
Member, Graduate Program in Biochemistry, Molecular and Structural Biology, JCCC Gene Regulation Program Area, Molecular Biology Institute
Researcher, Biochemistry, Development and Gene Regulation
Research Interests
The overall goal is to define and understand critical protein-DNA and protein-protein interactions that occur during regulation of transcription and other processes that require the opening of duplex DNA. Emphasis is placed on merging genetic and biochemical information. Particular attention is paid to integration to identify unifying concepts in different organisms and systems. One current project involves the biochemistry of the multi-protein complex TFIIH. TFIIH is a master regulator of DNA transactions and is needed for control of DNA transcription and repair and for replication timing. Defects in TFIIH lead to several human diseases including cancer and premature aging. Most diseases track to one of the 2 helicases that are needed to open DNA during transcription or repair. Recent data point to a critical role of the XPB helicase in coupling transcription initiation to RNA processing and this is a primary focus of current attention. Another project involves studying the transcription responses induced by stresses encountered during bacterial pathogenesis. The emphasis is on identifying the components required and learning how they interact. This involves both protein and DNA components. The current focus is on learning how bacteria adapt to the weak acid and osmotic shocks encountered in the gut and the crowded population that typically precedes pathogenesis. Cross-comparisons of these 2 seemingly different systems are used to learn unifying principles and well as important differences.

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.


A selected list of publications:

Tran Khiem, Gralla Jay D   The TFIIB tip domain couples transcription initiation to events involved in RNA processing The Journal of biological chemistry, 2010; 285(51): 39580-7.
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.
Fenton Mike S, Gralla Jay D   Roles for inhibitory interactions in the use of the -10 promoter element by sigma 70 holoenzyme J. Biol. Chem, 2003; 278(41): 39669-74.
Fenton Mike S, Gralla Jay D   Effect of DNA bases and backbone on sigma70 holoenzyme binding and isomerization using fork junction probes Nucleic Acids Res, 2003; 31(11): 2745-50.
Lee Shun Jin, Gralla Jay D   Open complex formation in vitro by sigma38 (rpoS) RNA polymerase: roles for region 2 amino acids J. Mol. Biol, 2003; 329(5): 941-8.
Lee Shun Jin, Gralla Jay D   Promoter use by sigma 38 (rpoS) RNA polymerase. Amino acid clusters for DNA binding and isomerization The Journal of biological chemistry, 2002; 277(49): 47420-7.
Lew Chih M, Gralla Jay D   New roles for conserved regions within a sigma 54-dependent enhancer-binding protein The Journal of biological chemistry, 2002; 277(44): 41517-24.
Choi Wai S, Yan Ming, Nusinow Dmitri, Gralla Jay D   In vitro transcription and start site selection in Schizosaccharomyces pombe Journal of molecular biology, 2002; 319(5): 1005-13.