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.

Systems Level Insights Into the Stress Response to UV Radiation in the Halophilic Archaeon Halobacterium NRC-1

Abstract: We report a remarkably high UV-radiation resistance in the extremely halophilic archaeon Halobacterium NRC-1 withstanding up to 110 J/m2 with no loss of viability. Gene knockout analysis in two putative photolyase-like genes (phr1 and phr2) implicated only phr2 in photoreactivation. The UV-response was further characterized by analyzing simultaneously, along with gene function and protein interactions inferred through comparative genomics approaches, mRNA changes for all 2400 genes during light and dark repair. In addition to photoreactivation, three other putative repair mechanisms were identified including d(CTAG) methylation-directed mismatch repair, four oxidative damage repair enzymes, and two proteases for eliminating damaged proteins. Moreover, a UV-induced down-regulation of many important metabolic functions was observed during light repair and seems to be a phenomenon shared by all three domains of life. The systems analysis has facilitated the assignment of putative functions to 26 of 33 key proteins in the UV response through sequence-based methods and/or similarities of their predicted three-dimensional structures to known structures in the PDB. Finally, the systems analysis has raised, through the integration of experimentally determined and computationally inferred data, many experimentally testable hypotheses that describe the metabolic and regulatory networks of Halobacterium NRC-1.

Discovering and linking public omics data sets using the Omics Discovery Index

Abstract: This work has been supported by the US NIH BD2K grant U54 GM114833 and a National Natural Science Foundation of China grant (61501071). A.I.N. is supported by US National Institute of Health grant (R01-GM-094231). Y.P.-R. is supported by BBSRC ‘PROCESS’ grant (BB/K01997X/1). M.B. is supported by Projects of International Cooperation and Exchanges grant (2014DFB30010). M.W. is supported by an NIH grant (5P41GM103484-07). J.A.V. and N.d.-T. are supported by the Wellcome Trust (grant WT101477MA). T.T. is supported by the BBSRC ‘ProteoGenomics’ grant (BB/L024225/1). E.W.D. and D.S.C. are supported in part by grant (U24 AI117966- 02S1). S.-A.S. is supported in part by US NIH BD2K grant (1U24AI117966-01). M.W. and N.Bandeira were supported by NIH grant (5P41GM103484-07). N.Bandeira was also partially supported as an Alfred P. Sloan Fellow. S.Subramaniam is supported by NIH grants U01 DK097430 and U01 CA198941

ATF3, an adaptive-response gene, enhances TGFβ signaling and cancer-initiating cell features in breast cancer cells

Abstract: The activating transcription factor 3 (ATF3) gene is induced by a variety of signals, including many of those encountered by cancer cells. We present evidence that ATF3 is induced by TGFβ in the MCF10CA1a breast cancer cells and plays an integral role for TGFβ to upregulate its target genes snail, slug and twist, and to enhance cell motility. Furthermore, ATF3 upregulates the expression of the TGFb gene itself, forming a positive-feedback loop for TGFβ signaling. Functionally, ectopic expression of ATF3 leads to morphological changes and alterations of markers consistent with epithelial-to-mesenchymal transition (EMT). It also leads to features associated with breast-cancer-initiating cells: increased CD24low–CD44high population of cells, mammosphere formation and tumorigenesis. Conversely, knockdown of ATF3 reduces EMT, CD24low–CD44high cells and mammosphere formation. Importantly, knocking down twist, a downstream target, reduces the ability of ATF3 to enhance mammosphere formation, indicating the functional significance of twist in ATF3 action. To our knowledge, this is the first report demonstrating the ability of ATF3 to enhance breast cancer-initiating cell features and to feedback on TGFβ. Because ATF3 is an adaptive-response gene and is induced by various stromal signals, these findings have significant implications for how the tumor microenvironment might affect cancer development.