JIC Student Brings Home New Expertise To Answer Question In
Working out the structure of a complex formed when a protein binds to DNA has proved to be key in understanding how an antibiotic-producing organism controls resistance to its own antibiotic, and may be an example of how other antibiotic producers regulate export to prevent self-toxicity.
The natural production of antibiotics by certain microorganisms is a complex and highly regulated process, not least because the organism making these compounds must protect itself from their toxic effects. Researchers at the John Innes Centre, which is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), have been studying the production of simocyclinone, produced by Streptomyces antibioticus, and in particular how the production of this potent antibiotic triggers an efficient pumping mechanism that exports the antibiotic from the cell.
Much of the work elucidating this protection mechanism has been carried out by Tung Le, a Vietnamese PhD student enrolled in the JIC's four-year rotation PhD programme. Tung, working under the supervision of Mark Buttner and David Lawson, showed that SimR, the protein Streptomyces antibioticus uses to regulate antibiotic export, can bind either to DNA or to the antibiotic itself, but crucially cannot bind to both. This means that when the antibiotic is around, SimR releases the DNA, which allows the expression of a gene that encodes a pump responsible for removing simocyclinone from the cell.
"This provides a mechanism that couples the potentially lethal biosynthesis of the antibiotic to its export, which has wider implications for resistance to clinically important antibiotics," commented Prof. Buttner. "However, we needed to know more detail about the interaction between SimR and DNA."
In this latest research, published in the journal Nucleic Acids Research, they show that the SimR protein has a novel ‘arm' and that cutting off this arm unexpectedly weakened SimR binding to DNA. To determine the function of this arm, the researchers needed to work out the crystal structure of the protein bound to DNA, something which hadn't been achieved in Norwich before.
To overcome this skills gap, Tung won both a Korner Travelling Fellowship and an EMBO Short-Term Travel Fellowship to visit the University of Texas M.D. Anderson Cancer Center, home to one of the leading laboratories specialising in this technique. Tung spent three months working in the labs of Richard Brennan and Maria Schumacher, learning how to solve the structures of protein-DNA complexes. He was then able to apply this to his own project.
Nucleic Acids Research - News
The invention also relates to methods of using such polypeptides, nucleic acids, or derivatives thereof, eg, in therapeutics, diagnostics, and as research tools. Another aspect of the present invention involves antibodies and other ligands which
In this latest research, published in the journal Nucleic Acids Research, they show that the SimR protein has a novel 'arm' and that cutting off this arm unexpectedly weakened SimR binding to DNA. To determine the function of this arm, the researchers
Viral breakdown of host cells converts particulate material to suspended or dissolved materials such as amino acids and nucleic acids, effectively resulting in the retention of nitrogen, phosphorous, and iron within the surface water.
basic calculations and the preparation of solutions; aseptic techniques; microscopy techniques; cell fractionation ; spectrophotometry; chromatography of small and large molecules: electrophoresis of proteins and nucleic acids and data analysis.
"It's robust and will provide a means to study biological protein-nucleic acid interactions." Work already is underway to modify the experimental instrumentation in the UO's stable and temperature-controlled High Stability Optics Lab to apply the
This Week in Nucleic Acids Research | The Daily Scan | GenomeWeb
This week, a team led by investigators at the New Jersey Medical School, present an "impartial evaluation of measurements of leukocyte telomere length by Southern blot of the terminal restriction fragments and quantitative PCR of telomere DNA content, expressed as the ratio of telomeric product [to] single copy gene product." In addition to presenting the results of its measurements of leukocyte telomere length assessments using this approach, the team also discusses "the ramifications of these findings with regard to measurements of telomere length/DNA content in epidemiological/clinical circumstances."
The University of Zurich's Nicole Wilson and Esther Stoeckli this week report their generation of "novel plasmid vectors that contain cell type-specific promoters/enhancers to drive the expression of a fluorescent marker," which, when followed directly by a miR30-RNAi transcript, "allow for direct tracing of cells experiencing gene silencing by the bright fluorescence." Further, the team suggests that the level of knockdown achieved using this vector-based approach "is sufficient to reproduce the expected pathfinding defects upon perturbation of genes with known axon guidance functions."
In another Nucleic Acids Research study, the team found that the "inactivation of DNA-PK [DNA-dependent protein kinase] and/or ATM led to reduced PNKP [polynucleotide kinase/phosphatase] at DNA damage sites."
Researchers in Taiwan show that, by integrating three experimental data sets — "including cap analysis of gene expression tags, TSS [transcriptional start sites] Seq libraries, and H3K4me3 chromatin signature derived from high-throughput sequencing analysis of gene initiation" — they were able to identify 847 human miRNA transcriptional start sites . The team also presents a "machine learning-based Support Vector Machine model ... to systematically identify representative TSSs for each miRNA gene," in its recent Nucleic Acids Research Fischer's group is seeking to understand the molecular mechanisms underlying learning and memory processes under physiological and pathological conditions. They are particularly interested in elucidating cognitive impairment associated with normal aging as well as the pathogenesis of mental and neurodegenerative diseases, such as anxiety disorders and Alzheimer’s disease. Using mice as models, Fischer and his team are attempting identify therapeutic strategies that would help to reinstate neuroplasticity, learning behavior, and the retrieval of lost long-term memories in patients.
RT @: Our microRNA body map paper is out in Nucleic Acids Research. It allows to predict miRNA functions.
RT @: Our microRNA body map paper is out in Nucleic Acids Research. It allows to predict miRNA functions.
Our microRNA body map paper is out in Nucleic Acids Research. It allows to predict miRNA functions.
This Week in Nucleic Acids Research
This Week in Nucleic Acids Research | The Daily Scan | GenomeWeb Nucleic Acids Research - Bookshelf
Nucleic acids research
Nucleic acids research
Nucleic acids research, Database issue
Methods in nucleic acids research
Biochemists, molecular biologists, immunologists, cell biologists, and geneticists will find this book invaluable for their research.Nucleic acids in chemistry and biology
1.2 THE ORIGINS OF NUCLEIC ACIDS RESEARCH Friedrich Miescher started his research career in Tübingen by looking into the physiology of human lymph cells. ...Day-to-day Report Directory
Nucleic Acids Research
Results of leading edge research into physical, chemical, biochemical and biological aspects of nucleic acids and proteins involved in nucleic acid metabolism and/or ...
Archive of "Nucleic Acids Research".
Nucleic Acids Research. Vols. 1 to 39; 1974 to 2011. Vol. 39. 2011. v.39 ... Articles from Nucleic Acids Research are provided here courtesy of. Oxford University ...
Nucleic Acids Research
Nucleic Acids Research - Wikipedia, the free encyclopedia
It covers research on nucleic acids, such as DNA and RNA, and related work. Some of its content is available under an open access license. ...
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The Nucleic Acid Database (NDB) is appropriate for atomic co-ordinate ... protein sequences that are the result of translation of nucleic acid sequences. ...