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Daniel P Zimmer

Publications and source records attributed to Daniel P Zimmer.

4 recordsLinked to original sources
PubMed2004

Genome image programs: visualization and interpretation of Escherichia coli microarray experiments.

We have developed programs to facilitate analysis of microarray data in Escherichia coli. They fall into two categories: manipulation of microarray images and identification of known biological relationships among lists of genes. A program in the first category arranges spots from glass-slide DNA microarrays according to their position in the E. coli genome and displays them compactly in genome order. The resulting genome image is presented in a web browser with an image map that allows the user to identify genes in the reordered image. Another program in the first category aligns genome images from two or more experiments. These images assist in visualizing regions of the genome with common transcriptional control. Such regions include multigene operons and clusters of operons, which are easily identified as strings of adjacent, similarly colored spots. The images are also useful for assessing the overall quality of experiments. The second category of programs includes a database and a number of tools for displaying biological information about many E. coli genes simultaneously rather than one gene at a time, which facilitates identifying relationships among them. These programs have accelerated and enhanced our interpretation of results from E. coli DNA microarray experiments. Examples are given.

Chromosome Mapping↗
PubMed2003

Structural origins of adenine-tract bending.

DNA sequences containing short adenine tracts are intrinsically curved and play a role in transcriptional regulation. Despite many high-resolution NMR and x-ray studies, the origins of curvature remain disputed. Long-range restraints provided by 85 residual dipolar couplings were measured for a DNA decamer containing an adenine (A)(4)-tract and used to refine the structure. The overall bend in the molecule is a result of in-phase negative roll in the A-tract and positive roll at its 5' junction, as well as positive and negative tilt inside the A-tract and near its junctions. The bend magnitude and direction obtained from NMR structures is 9.0 degrees into the minor groove in a coordinate frame located at the third AT base pair. We evaluated long-range and wedge models for DNA curvature and concluded that our data for A-tract curvature are best explained by a "delocalized bend" model. The global bend magnitude and direction of the NMR structure are in excellent agreement with the junction model parameters used to rationalize gel electrophoretic data and with preliminary results of a cyclization kinetics assay from our laboratory.

Adenine↗
PubMed2003

Integrating transcriptional and metabolite profiles to direct the engineering of lovastatin-producing fungal strains.

We describe a method to decipher the complex inter-relationships between metabolite production trends and gene expression events, and show how information gleaned from such studies can be applied to yield improved production strains. Genomic fragment microarrays were constructed for the Aspergillus terreus genome, and transcriptional profiles were generated from strains engineered to produce varying amounts of the medically significant natural product lovastatin. Metabolite detection methods were employed to quantify the polyketide-derived secondary metabolites lovastatin and (+)-geodin in broths from fermentations of the same strains. Association analysis of the resulting transcriptional and metabolic data sets provides mechanistic insight into the genetic and physiological control of lovastatin and (+)-geodin biosynthesis, and identifies novel components involved in the production of (+)-geodin, as well as other secondary metabolites. Furthermore, this analysis identifies specific tools, including promoters for reporter-based selection systems, that we employed to improve lovastatin production by A. terreus.

Aspergillus↗