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Dive into the research topics where Linda E. Hyman is active.

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Featured researches published by Linda E. Hyman.


Applied and Environmental Microbiology | 2006

Effects of Low-Shear Modeled Microgravity on Cell Function, Gene Expression, and Phenotype in Saccharomyces cerevisiae

Boloroo Purevdorj-Gage; Kathy B. Sheehan; Linda E. Hyman

ABSTRACT Only limited information is available concerning the effects of low-shear modeled microgravity (LSMMG) on cell function and morphology. We examined the behavior of Saccharomyces cerevisiae grown in a high-aspect-ratio vessel, which simulates the low-shear and microgravity conditions encountered in spaceflight. With the exception of a shortened lag phase (90 min less than controls; P < 0.05), yeast cells grown under LSMMG conditions did not differ in growth rate, size, shape, or viability from the controls but did differ in the establishment of polarity as exhibited by aberrant (random) budding compared to the usual bipolar pattern of controls. The aberrant budding was accompanied by an increased tendency of cells to clump, as indicated by aggregates containing five or more cells. We also found significant changes (greater than or equal to twofold) in the expression of genes associated with the establishment of polarity (BUD5), bipolar budding (RAX1, RAX2, and BUD25), and cell separation (DSE1, DSE2, and EGT2). Thus, low-shear environments may significantly alter yeast gene expression and phenotype as well as evolutionary conserved cellular functions such as polarization. The results provide a paradigm for understanding polarity-dependent cell responses to microgravity ranging from pathogenesis in fungi to the immune response in mammals.


BMC Genomics | 2007

Yeast genomic expression patterns in response to low-shear modeled microgravity

Kathy B. Sheehan; Kate McInnerney; Boloroo Purevdorj-Gage; Sara D. Altenburg; Linda E. Hyman

The low-shear microgravity environment, modeled by rotating suspension culture bioreactors called high aspect ratio vessels (HARVs), allows investigation in ground-based studies of the effects of microgravity on eukaryotic cells and provides insights into the impact of space flight on cellular physiology. We have previously demonstrated that low-shear modeled microgravity (LSMMG) causes significant phenotypic changes of a select group of Saccharomyces cerevisiae genes associated with the establishment of cell polarity, bipolar budding, and cell separation. However, the mechanisms cells utilize to sense and respond to microgravity and the fundamental gene expression changes that occur are largely unknown. In this study, we examined the global transcriptional response of yeast cells grown under LSMMG conditions using DNA microarray analysis in order to determine if exposure to LSMMG results in changes in gene expression.ResultsLSMMG differentially changed the expression of a significant number of genes (1372) when yeast cells were cultured for either five generations or twenty-five generations in HARVs, as compared to cells grown under identical conditions in normal gravity. We identified genes in cell wall integrity signaling pathways containing MAP kinase cascades that may provide clues to novel physiological responses of eukaryotic cells to the external stress of a low-shear modeled microgravity environment. A comparison of the microgravity response to other environmental stress response (ESR) genes showed that 26% of the genes that respond significantly to LSMMG are involved in a general environmental stress response, while 74% of the genes may represent a unique transcriptional response to microgravity. In addition, we found changes in genes involved in budding, cell polarity establishment, and cell separation that validate our hypothesis that phenotypic changes observed in cells grown in microgravity are reflected in genome-wide changes.This study documents a considerable response to yeast cell growth in low-shear modeled microgravity that is evident, at least in part, by changes in gene expression. Notably, we identified genes that are involved in cell signaling pathways that allow cells to detect environmental changes, to respond within the cell, and to change accordingly, as well as genes of unknown function that may have a unique transcriptional response to microgravity. We also uncovered significant changes in the expression of many genes involved in cell polarization and bud formation that correlate well with the phenotypic effects observed in yeast cells when grown under similar conditions. These results are noteworthy as they have implications for human space flight.


Genomics, Proteomics & Bioinformatics | 2008

Increased Filamentous Growth of Candida albicans in Simulated Microgravity

Sara D. Altenburg; Sheila M. Nielsen-Preiss; Linda E. Hyman

Knowledge of simulated microgravity (SMG)-induced changes in the pathogenicity of microorganisms is important for success of long-term spaceflight. In a previous study using the high aspect ratio vessel bioreactor, we showed that the yeast species Saccharomyces cerevisiae underwent a significant phenotypic response when grown in modeled microgravity, which was reflected in the analysis of gene expression profiles. In this study, we establish that Candida albicans responds to SMG in a similar fashion, demonstrating that there is a conserved response among yeast to this environmental stress. We also report that the growth of C. albicans in SMG results in a morphogenic switch that is consistent with enhanced pathogenicity. Specifically, we observed an increase in filamentous forms of the organism and accompanying changes in the expression of two genes associated with the yeast-hyphal transition. The morphological response may have significant implications for astronauts’ safety, as the fungal pathogen may become more virulent during spaceflight.


PLOS ONE | 2013

Spaceflight enhances cell aggregation and random budding in Candida albicans.

Aurélie Crabbé; Sheila M. Nielsen-Preiss; Christine M. Woolley; Jennifer Barrila; Kent L. Buchanan; James McCracken; Diane O. Inglis; Stephen C. Searles; Mayra Nelman-Gonzalez; C. Mark Ott; James W. Wilson; Duane L. Pierson; Heidemarie M. Stefanyshyn-Piper; Linda E. Hyman; Cheryl A. Nickerson

This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans–induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.


Developmental Biology | 1988

Post-translational control of ribosomal protein L1 accumulation in Xenopus oocytes

Ellen Z. Baum; Linda E. Hyman; W.Michael Wormington

A functional ribosomal protein mRNA, encoding the 60 S subunit protein L1, has been synthesized in vitro using bacteriophage SP6 RNA polymerase. This mRNA directs the synthesis of a product indistinguishable from L1 protein purified from Xenopus ovarian ribosomes. Our results show that L1 synthesis in stage VI oocytes increases in response to microinjection of exogenous SP6-L1 mRNA, but excess L1 protein is not stably accumulated. These results indicate that dosage compensation does not occur at the translational level for this ribosomal protein mRNA and that the abundance of this protein in fully grown oocytes is subject to post-translational regulation.


Biochimica et Biophysica Acta | 2000

Novel roles for elongin C in yeast.

Tanya Jackson; Edward Kwon; Anna M. Chachulska; Linda E. Hyman

Mammalian Elongin C is a 112-amino acid protein that binds to the von Hippel-Lindau (VHL) tumor suppressor and to Elongin A, the transcriptionally active subunit of the RNA polymerase II elongation factor, SIII. It is conserved in eukaryotic cells, as homologs have been identified in Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans. The mammalian protein is thought to function as part of a ubiquitin targeting E3 ligase, yet the function in yeast has not been determined. In this report we examine the role of Elongin C in yeast and establish that yeast Elongin C may function in a mode distinct from its role as an E3 ligase. The RNA is expressed ubiquitously, albeit at low levels. Two hybrid analyses demonstrate that Elongin C in yeast interacts with a specific set of proteins that are involved in the stress response. This suggests a novel role for Elongin C and provides insights into additional potential functions in mammalian cells.


Developmental Biology | 1982

Some somatic sequences are absent or exceedingly rare in Xenopus oocyte RNA

Ulrich Schafer; Lynn Golden; Linda E. Hyman; Hildur V. Colot; Michael Rosbash

Abstract A variety of Xenopus laevis cDNA clones derived from somatic cell RNAs were hybridized to oocyte pA + RNA separated on Northern gels. We were unable to detect oocyte pA + sequences complementary to three undefined tadpole cDNA clones. With one of these clones, a complex pattern of bands appears during embryogenesis. With the other two clones, a single band appears. Two additional tadpole clones hybridize to both oocyte and tadpole RNA, but yield a more complex RNA pattern from embryos than from oocytes. One of these additional tadpole clones has complementarity to actin DNA, suggesting that the additional RNA band which appears during embryogenesis is α-actin mRNA ( E. A. Sturgess, J. E. M. Ballantine, H. R. Woodland, P. R. Mohun, C. D. Lane, and G. J. Dimitriadis, 1980 , J. Embryol. Exp. Morphol. 58, 303–320). We have also failed to detect hybridization to oocyte pA + RNA with one vitellogenin and three adult globin cDNA clones. Reconstruction experiments with purified globin mRNA from anemic adult blood cells set the lower level of sensitivity for globin mRNA at one part in 10 6 . The data suggest that some Xenopus mRNA sequences are absent or very rare in the oocyte pA + RNA population.


Archive | 1984

Accumulation and Behavior of mRNA During Oogenesis and Early Embryogenesis of Xenopus Laevis

Linda E. Hyman; Hildur V. Colot; Michael Rosbash

Studies examining the messenger RNA population present in Xenopus laevis oocytes and early embryos are discussed. There may be two classes of mRNA present in the oocyte, one which is used by the developing germ cell and the other which is synthesized during early oogenesis and stored for translation after fertilization. During oocyte maturation the mRNA population undergoes a dramatic qualitative change in which the length of the pA tail is altered. The behavior of individual sequences, including actin and ribosomal proteins, is described during maturation and early embryogenesis.


Biochemistry and Molecular Biology Education | 2015

Leading Change: Curriculum Reform in Graduate Education in the Biomedical Sciences.

Shoumita Dasgupta; Karen Symes; Linda E. Hyman

The Division of Graduate Medical Sciences at the Boston University School of Medicine houses numerous dynamic graduate programs. Doctoral students began their studies with laboratory rotations and classroom training in a variety of fundamental disciplines. Importantly, with 15 unique pathways of admission to these doctoral programs, there were also 15 unique curricula. Departments and programs offered courses independently, and students participated in curricula that were overlapping combinations of these courses. This system created curricula that were not coordinated and that had redundant course content as well as content gaps. A partnership of key stakeholders began a curriculum reform process to completely restructure doctoral education at the Boston University School of Medicine. The key pedagogical goals, objectives, and elements designed into the new curriculum through this reform process created a curriculum designed to foster the interdisciplinary thinking that students are ultimately asked to utilize in their research endeavors. We implemented comprehensive student and peer evaluation of the new Foundations in Biomedical Sciences integrated curriculum to assess the new curriculum. Furthermore, we detail how this process served as a gateway toward creating a more fully integrated graduate experience, under the umbrella of the Program in Biomedical Sciences.


Microbiology and Molecular Biology Reviews | 1999

Formation of mRNA 3′ Ends in Eukaryotes: Mechanism, Regulation, and Interrelationships with Other Steps in mRNA Synthesis

Jing Zhao; Linda E. Hyman; Claire Moore

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