Science Seen; Models and Targets; Interdisciplinary Research

Front Page | Science Seen; Models and Targets; Interdisciplinary Research SCIENCE SEEN Courtesy of Science Photo Library ROCKETTES MATERIAL? This diatom, belonging to the Bacillariophyceae class of minute planktonic unicellular or colonial algae, could be called the daddy longlegs of the unicellular marine world. Found in plankton, this Bacteriastrum delicatulum has very ornate cell walls made of silica; its legs may aid flotation. Plankton forms the basis for the entire marine food chain. This colored image was captured by a scanning electron microscope. MODELS AND TARGETS HIC-down Johns Hopkins School of Medicine researchers developed a murine model to investigate the role of the HIC1 gene, which encodes a zinc-finger transcription factor. HIC1 is hypermethylated (in cancer) and therefore transcriptionally silent in many cancer types. HIC1-/- mice were not viable. But, heterozygotes developed normally for about a year, and then a variety of sex-dependent tumors arose. Males displayed epithelial cancers and females developed lymphomas and sarcomas. In most tumor tissue, researchers found at least one promoter of the wild-type HIC1 allele to be hypermethylated. The scientists postulate that HIC1 is the first hypermethylated tumor-suppressor candidate to have been demonstrated with a murine knockout (W.Y. Chen et al., "Heterozygous disruption of the Hic1 predisposes mice to a gender dependent spectrum of malignant tumors," Nat Gen, 33:197-202, February 2003). DEP-ressed Salt Lake City's Myriad Genetics is following up on a yet unpublished study of 400 Utah families with histories of major depression. The investigation implicated a gene temporarily called DEP1 (not the transmembrane protein tyrosine phosphatase involved in cell adhesion). While Myriad researchers are careful not to tip their hand, they say this DEP1 appears to affect a depression pathway independent of the one targeted by the most common class of drugs. These are the selective serotonin re-uptake inhibitors that include Prozac®, Zoloft®, and Paxil®. Myriad is currently using protein interaction analyses to identify targets within the DEP1 pathway. Abbott Laboratories of Abbott Park, Ill. paid Myriad $1 million (US) for drug development rights. --Brendan A. Maher INTERDISCIPLINARY RESEARCH These papers were selected from multiple disciplines of the Faculty of 1000, a Web-based literature awareness tool. (www.facultyof1000.com) S.H. Shi et al., "Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity," Cell, 112:63-75, Jan. 10, 2003. "In hippocampal neurons, axonal polarity results from phosphatidyl-inositol 3-kinase directing the localization of the polarity proteins mPar3 and mPar6 to one of a group of neurites that the cell initially extends....The resulting axon contains most of the mPar3 and mPar6 protein. Expressing mPar3 unbiquitously throughout these cells blocks the ability of these cells to specify an axon." --Gordon J. Fishell R.S. Kamath et al., "Systematic functional analysis of the Caenorhabditis elegans genome using RNAi," Nature, 421:231-7, Jan. 16, 2003. "... functional tests were performed on 86% of all 19,427 currently predicted genes in C. elegans, using the method of RNA interference by bacterial feeding.... 1722 genes were observed to give mutant phenotypes, which could be grouped into some 20 broad classes. Evidence was obtained for large-scale functional clustering in many regions of the genome and for sex chromosome differentiation." --Jonathan Hodgkin T.I. Lee et al., "Transcriptional regulatory networks in Saccharomyces cerevisiae," Science, 298:799-804, Oct 25, 2002. "Using S. cerevisiae as a model system, this paper identifies recurrent network motifs: autoregulation, multicomponent loops (i.e., indirect autoregulation), feedforward loops, single input (one regulator controls several targets), multiinput (several regulators cooperate to control several targets), and regulatory chains (cascades). It is demonstrated how these motifs are combined to coordinate cell cycle, metabolism, environmental responses, or development." --Regine Hengge-Aronis

Science Seen; Models and Targets; Interdisciplinary Research

Front Page | Science Seen; Models and Targets; Interdisciplinary Research

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