Institute for Systems Biology

About: Institute for Systems Biology is a nonprofit organization based out in Seattle, Washington, United States. It is known for research contribution in the topics: Population & Proteomics. The organization has 1277 authors who have published 2777 publications receiving 353165 citations.

Intersection of the Kap123p-Mediated Nuclear Import and Ribosome Export Pathways

Abstract: Kap123p is a yeast beta-karyopherin that imports ribosomal proteins into the nucleus prior to their assembly into preribosomal particles. Surprisingly, Kap123p is not essential for growth, under normal conditions. To further explore the role of Kap123p in nucleocytoplasmic transport and ribosome biogenesis, we performed a synthetic fitness screen designed to identify genes that interact with KAP123. Through this analysis we have identified three other karyopherins, Pse1p/Kap121p, Sxm1p/Kap108p, and Nmd5p/Kap119p. We propose that, in the absence of Kap123p, these karyopherins are able to supplant Kap123p's role in import. In addition to the karyopherins, we identified Rai1p, a protein previously implicated in rRNA processing. Rai1p is also not essential, but deletion of the RAI1 gene is deleterious to cell growth and causes defects in rRNA processing, which leads to an imbalance of the 60S/40S ratio and the accumulation of halfmers, 40S subunits assembled on polysomes that are unable to form functional ribosomes. Rai1p localizes predominantly to the nucleus, where it physically interacts with Rat1p and pre-60S ribosomal subunits. Analysis of the rai1/kap123 double mutant strain suggests that the observed genetic interaction results from an inability to efficiently export pre-60S subunits from the nucleus, which arises from a combination of compromised Kap123p-mediated nuclear import of the essential 60S ribosomal subunit export factor, Nmd3p, and a DeltaRAI1-induced decrease in the overall biogenesis efficiency.

Initial Proteome Analysis of Model Microorganism Haemophilus influenzae Strain Rd KW20

Abstract: The proteome of Haemophilus influenzae strain Rd KW20 was analyzed by liquid chromatography (LC) coupled with ion trap tandem mass spectrometry (MS/MS). This approach does not require a gel electrophoresis step and provides a rapidly developed snapshot of the proteome. In order to gain insight into the central metabolism of H. influenzae, cells were grown microaerobically and anaerobically in a rich medium and soluble and membrane proteins of strain Rd KW20 were proteolyzed with trypsin and directly examined by LC-MS/MS. Several different experimental and computational approaches were utilized to optimize the proteome coverage and to ensure statistically valid protein identification. Approximately 25% of all predicted proteins (open reading frames) of H. influenzae strain Rd KW20 were identified with high confidence, as their component peptides were unambiguously assigned to tandem mass spectra. Approximately 80% of the predicted ribosomal proteins were identified with high confidence, compared to the 33% of the predicted ribosomal proteins detected by previous two-dimensional gel electrophoresis studies. The results obtained in this study are generally consistent with those obtained from computational genome analysis, two-dimensional gel electrophoresis, and whole-genome transposon mutagenesis studies. At least 15 genes originally annotated as conserved hypothetical were found to encode expressed proteins. Two more proteins, previously annotated as predicted coding regions, were detected with high confidence; these proteins also have close homologs in related bacteria. The direct proteomics approach to studying protein expression in vivo reported here is a powerful method that is applicable to proteome analysis of any (micro)organism.

Evolutionary history of Tibetans inferred from whole-genome sequencing.

Abstract: The indigenous people of the Tibetan Plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude. Recent studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high altitude-adaptation and originated in an archaic Denisovan-related population. We sequenced the whole-genomes of 27 Tibetans and conducted analyses to infer a detailed history of demography and natural selection of this population. We detected evidence of population structure between the ancestral Han and Tibetan subpopulations as early as 44 to 58 thousand years ago, but with high rates of gene flow until approximately 9 thousand years ago. The CMS test ranked EPAS1 and EGLN1 as the top two positive selection candidates, and in addition identified PTGIS, VDR, and KCTD12 as new candidate genes. The advantageous Tibetan EPAS1 haplotype shared many variants with the Denisovan genome, with an ancient gene tree divergence between the Tibetan and Denisovan haplotypes of about 1 million years ago. With the exception of EPAS1, we observed no evidence of positive selection on Denisovan-like haplotypes.

Faint High-Latitude Carbon Stars Discovered by the Sloan Digital Sky Survey: Methods and Initial Results

Abstract: We report the discovery of 39 faint high-latitude carbon stars (FHLCs) from Sloan Digital Sky Survey (SDSS) commissioning data The objects, each selected photometrically and verified spectroscopically, range over 166 < r* < 200 and show a diversity of temperatures as judged by both colors and NaD line strengths Although a handful of these stars were previously known, these objects are, in general, too faint and too warm to be effectively identified in other modern surveys such as the Two Micron All Sky Survey, nor are their red/near-IR colors particularly distinctive The implied surface density of FHLCs in this magnitude range is uncertain at this preliminary stage of the survey because of completeness corrections but is clearly greater than 005 deg-2 At the completion of the Sloan survey, there will be many hundred homogeneously selected and observed FHLCs in this sample We present proper-motion measures for each object, indicating that the sample is a mixture of extremely distant (greater than 100 kpc) halo giant stars, useful for constraining halo dynamics, and members of the recently recognized exotic class of very nearby dwarf carbon (dC) stars The broadband colors of the two populations are indistinguishable Motions, and thus dC classification, are inferred for 40%–50% of the sample, depending on the level of statistical significance invoked The new list of dC stars presented here, although selected from only a small fraction of the final SDSS, doubles the number of such objects found by all previous methods The observed kinematics suggest that the dwarfs occupy distinct halo and disk populations The coolest FHLCs with detectable proper motions in our sample also display multiple CaH bands in their spectra It may be that CaH is another long-sought, low-resolution, spectroscopic luminosity discriminant between dC's and distant faint giants, at least for the cooler stars