Weinzierl, Robert - Imperial College London - Department of Life Sciences, Biochemistry and Biotechnology

个人简介

Dr. Weinzierl's research focuses on the structure and function of archaeal and eukaryotic RNA polymerases. Archaeal RNA polymerases are very similar to eukaryotic RNA polymerase II and provide one of the best model systems for discovering more about gene regulatory mechanisms operating in eukaryotic organisms. In a technical tour de force the group has recently succeeded in assembling an active archaeal RNA polymerase from 12 different recombinant subunits. The synthetic enzyme is capable of carrying out all known functions, including promoter-specific transcription and responding to transcriptional activators. It is therefore possible to use this unique experimental system to study the effects of mutations on various aspects of RNA polymerase function. The laboratory currently focuses on the development of robotic high-throughput systems capable of producing and assaying recombinant RNA polymerases containing a variety of targeted mutations in key regions of the enzyme. Such approaches will provide new insights into a central process of gene regulation.

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Scholes NS, Weinzierl ROJ, 2016, Molecular Dynamics of "Fuzzy" Transcriptional Activator-Coactivator Interactions, PLOS COMPUTATIONAL BIOLOGY, Vol: 12, ISSN: 1553-734X Wiesler SC, Weinzierl RO, 2015, Robotic high-throughput purification of affinity-tagged recombinant proteins., Methods Mol Biol, Vol: 1286, Pages: 97-106 Nicod SS, Weinzierl ROJ, Burchell L, Escalera-Maurer A, James EH, Wigneshweraraj Set al., 2014, Systematic mutational analysis of the LytTR DNA binding domain of Staphylococcus aureus virulence gene transcription factor AgrA, NUCLEIC ACIDS RESEARCH, Vol: 42, Pages: 12523-12536, ISSN: 0305-1048 Weinzierl ROJ, 2013, The RNA Polymerase Factory and Archaeal Transcription, CHEMICAL REVIEWS, Vol: 113, Pages: 8350-8376, ISSN: 0009-2665 Wiesler SC, Weinzierl ROJ, Buck M, 2013, An aromatic residue switch in enhancer-dependent bacterial RNA polymerase controls transcription intermediate complex activity, NUCLEIC ACIDS RESEARCH, Vol: 41, Pages: 5874-5886, ISSN: 0305-1048 Wiesler SC, Werner F, Weinzierl RO, 2013, Promoter independent abortive transcription assays unravel functional interactions between TFIIB and RNA polymerase., Methods Mol Biol, Vol: 977, Pages: 217-227 Wiesler SC, Weinzierl ROJ, 2012, High-throughput Purification of Affinity-tagged Recombinant Proteins, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X Heindl H, Greenwell P, Weingarten N, Kiss T, Terstyanszky G, Weinzierl ROJet al., 2011, Cation-pi interactions induce kinking of a molecular hinge in the RNA polymerase bridge-helix domain, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 39, Pages: 31-35, ISSN: 0300-5127 Jovanovic M, Burrows PC, Bose D, Camara B, Wiesler S, Zhang X, Wigneshweraraj S, Weinzierl ROJ, Buck Met al., 2011, Activity Map of the Escherichia coli RNA Polymerase Bridge Helix, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 14469-14479, ISSN: 0021-9258 Weinzierl RO, Wiesler SC, 2011, Revealing the functions of TFIIB., Transcription, Vol: 2, Pages: 254-257 Weinzierl ROJ, 2011, The Bridge Helix of RNA Polymerase Acts as a Central Nanomechanical Switchboard for Coordinating Catalysis and Substrate Movement, ARCHAEA-AN INTERNATIONAL MICROBIOLOGICAL JOURNAL, ISSN: 1472-3646 Wiesler SC, Weinzierl ROJ, 2011, The linker domain of basal transcription factor TFIIB controls distinct recruitment and transcription stimulation functions, NUCLEIC ACIDS RESEARCH, Vol: 39, Pages: 464-474, ISSN: 0305-1048 Cámara B, Liu M, Reynolds J, Shadrin A, Liu B, Kwok K, Simpson P, Weinzierl R, Severinov K, Cota E, Matthews S, Wigneshweraraj SRet al., 2010, T7 phage protein Gp2 inhibits the Escherichia coli RNA polymerase by antagonizing stable DNA strand separation near the transcription start site., Proc Natl Acad Sci USA, Vol: 107, Pages: 2247-2252 Weinzierl RO, 2010, Chromatin Topology, 0116453.2 Weinzierl RO, Axton JM, Ghysen A, Akam Met al., 2010, Ultrabithorax mutations in constant and variable regions of the protein coding sequence., Genes & Dev., Vol: 1, Pages: 386-397 Weinzierl ROJ, 2010, Nanomechanical constraints acting on the catalytic site of cellular RNA polymerases, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 38, Pages: 428-432, ISSN: 0300-5127 Weinzierl ROJ, 2010, The nucleotide addition cycle of RNA polymerase is controlled by two molecular hinges in the Bridge Helix domain, BMC BIOLOGY, Vol: 8, ISSN: 1741-7007 Xiao Y, Wigneshweraraj SR, Weinzierl R, Wang YP, Buck Met al., 2010, Construction and functional analyses of a comprehensive sigma54 site-directed mutant library using alanine-cysteine mutagenesis., Nucleic Acids Res., Vol: 37, Pages: 4482-4497 Nottebaum S, Tan L, Trzaska D, Carney HC, Weinzierl ROJet al., 2008, The RNA polymerase factory: a robotic in vitro assembly platform for high-throughput production of recombinant protein complexes, NUCLEIC ACIDS RESEARCH, Vol: 36, Pages: 245-252, ISSN: 0305-1048 Tan L, Wiesler S, Trzaska D, Carney HC, Weinzierl ROet al., 2008, Bridge helix and trigger loop perturbations generate superactive RNA polymerases., J Biol, Vol: 7