Advertisement

Yeast in Space

  • Timothy G. Hammond
  • Holly H Birdsall
Living reference work entry

Abstract

Humans and yeast have traveled together through a long history of terrestrial explorations and will continue to do so as mankind explores space. Candida species of yeast accompany us as part of our microbiome and humans will find ways to carry Saccharomyces species of yeast with them on their space travels in order to make bread and beer/wine. In addition to its health and gastronomic roles, yeasts have also proven to be highly useful tools for exploring the biologic impacts of the space environment. An international consortium has produced a library of clones in which each of the ~6,200 known open reading frames of the yeast Saccharomyces cerevisiae has been systematically deleted. For fitness profiling, this library of clones is exposed to a stressor such as galactic cosmic radiation, changes in mass transport, or shear stress and allowed to proliferate for up to 100 generations. By systematically identifying those genes and gene pathways that are required to resistant exposure to spaceflight stimuli, the mediating and buffering gene pathways can be delineated, which can be augmented experimentally to identify countermeasures. At the end of the exposure, the relative abundance of each clone is enumerated by next-generation sequencing. Those clones carrying a deletion of a gene needed for survival in the presence of spaceflight stimuli have reduced growth or fitness. Secondarily, these techniques can be applied to assess drug-induced changes during spaceflight. Broad stimulus libraries, including radiation types and radiomimetics, collected and assessed at 20+ generations are available for comparison.

Notes

Acknowledgments

National Aeronautics and Space Association grants NNX13AN32G and NNX12AM93G and the Department of Veterans Affairs supported this work. Contents do not represent the view of the Department of Veterans Affairs or the United States of America.

References

  1. Acharya A, Das I, Chandhok D, Saha T (2010) Redox regulation in cancer: a double-edged sword with therapeutic potential. Oxidative Med Cell Longev 3(1):23–34.  https://doi.org/10.4161/oxim.3.1.10095CrossRefGoogle Scholar
  2. Altenburg SD, Nielsen-Preiss SM, Hyman LE (2008) Increased filamentous growth of Candida albicans in simulated microgravity. Genomics Proteomics Bioinformatics/Beijing Genomics Institute 6(1):42–50.  https://doi.org/10.1016/S1672-0229(08)60019-4CrossRefGoogle Scholar
  3. Baudin A, Ozier-Kalogeropoulos O, Denouel A, Lacroute F, Cullin C (1993) A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res 21(14):3329–3330CrossRefGoogle Scholar
  4. Berry D, Volz PA (1979) Phosphate uptake in Saccharomyces cerevisiae Hansen wild type and phenotypes exposed to space flight irradiation. Appl Environ Microbiol 38(4):751–753PubMedPubMedCentralGoogle Scholar
  5. Berry DB, Guan Q, Hose J, Haroon S, Gebbia M, Heisler LE, Nislow C, Giaever G, Gasch AP (2011) Multiple means to the same end: the genetic basis of acquired stress resistance in yeast. PLoS Genet 7(11):e1002353.  https://doi.org/10.1371/journal.pgen.1002353CrossRefPubMedPubMedCentralGoogle Scholar
  6. Birrell GW, Brown JA, Wu HI, Giaever G, Chu AM, Davis RW, Brown JM (2002) Transcriptional response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents. Proc Natl Acad Sci USA 99(13):8778–8783.  https://doi.org/10.1073/pnas.132275199CrossRefPubMedGoogle Scholar
  7. Blackman RK, Cheung-Ong K, Gebbia M, Proia DA, He S, Kepros J, Jonneaux A, Marchetti P, Kluza J, Rao PE, Wada Y, Giaever G, Nislow C (2012) Mitochondrial electron transport is the cellular target of the oncology drug elesclomol. PLoS One 7(1):e29798.  https://doi.org/10.1371/journal.pone.0029798CrossRefPubMedPubMedCentralGoogle Scholar
  8. Botstein D, Chervitz SA, Cherry JM (1997) Yeast as a model organism. Science 277(5330):1259–1260CrossRefGoogle Scholar
  9. Bradamante S, Villa A, Versari S, Barenghi L, Orlandi I, Vai M (2010) Oxidative stress and alterations in actin cytoskeleton trigger glutathione efflux in Saccharomyces cerevisiae. Biochim Biophys Acta 1803(12):1376–1385.  https://doi.org/10.1016/j.bbamcr.2010.07.007CrossRefPubMedGoogle Scholar
  10. Cap M, Vachova L, Palkova Z (2009) Yeast colony survival depends on metabolic adaptation and cell differentiation rather than on stress defense. J Biol Chem 284(47):32572–32581.  https://doi.org/10.1074/jbc.M109.022871CrossRefPubMedPubMedCentralGoogle Scholar
  11. Cap M, Stepanek L, Harant K, Vachova L, Palkova Z (2012a) Cell differentiation within a yeast colony: metabolic and regulatory parallels with a tumor-affected organism. Mol Cell 46(4):436–448.  https://doi.org/10.1016/j.molcel.2012.04.001CrossRefPubMedGoogle Scholar
  12. Cap M, Vachova L, Palkova Z (2012b) Reactive oxygen species in the signaling and adaptation of multicellular microbial communities. Oxidative Med Cell Longev 2012:976753.  https://doi.org/10.1155/2012/976753CrossRefGoogle Scholar
  13. Chan JN, Nislow C, Emili A (2010) Recent advances and method development for drug target identification. Trends Pharmacol Sci 31(2):82–88.  https://doi.org/10.1016/j.tips.2009.11.002CrossRefPubMedGoogle Scholar
  14. Cheung-Ong K, Song KT, Ma Z, Shabtai D, Lee AY, Gallo D, Heisler LE, Brown GW, Bierbach U, Giaever G, Nislow C (2012) Comparative Chemogenomics to examine the mechanism of action of DNA-targeted platinum-Acridine anticancer agents. ACS Chem Biol 7(11):1892–1901.  https://doi.org/10.1021/cb300320dCrossRefPubMedPubMedCentralGoogle Scholar
  15. Cheung-Ong K, Giaever G, Nislow C (2013) DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology. Chem Biol 20(5):648–659.  https://doi.org/10.1016/j.chembiol.2013.04.007CrossRefPubMedGoogle Scholar
  16. Coleman CB, Allen PL, Rupert M, Goulart C, Hoehn A, Stodieck LS, Hammond TG (2008) Novel Sfp1 transcriptional regulation of Saccharomyces cerevisiae gene expression changes during spaceflight. Astrobiology 8(6):1071–1078.  https://doi.org/10.1089/ast.2007.0211CrossRefPubMedGoogle Scholar
  17. Collins FS (2011) Mining for therapeutic gold. Nat Rev Drug Discov 10(6):397.  https://doi.org/10.1038/nrd3461CrossRefPubMedPubMedCentralGoogle Scholar
  18. Dickson KJ (1991) Summary of biological spaceflight experiments with cells. ASGSB Bulletin 4(2):151–260PubMedGoogle Scholar
  19. Dujon B (2010) Yeast evolutionary genomics. Nat Rev Genet 11(7):512–524.  https://doi.org/10.1038/nrg2811CrossRefPubMedGoogle Scholar
  20. Fukuda T, Fukuda K, Takahashi A, Ohnishi T, Nakano T, Sato M, Gunge N (2000) Analysis of deletion mutations of the rpsL gene in the yeast Saccharomyces cerevisiae detected after long-term flight on the Russian space station Mir. Mutat Res 470(2):125–132CrossRefGoogle Scholar
  21. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11(12):4241–4257CrossRefGoogle Scholar
  22. Gasch AP, Huang M, Metzner S, Botstein D, Elledge SJ, Brown PO (2001) Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. Mol Biol Cell 12(10):2987–3003CrossRefGoogle Scholar
  23. Giaever G, Flaherty P, Kumm J, Proctor M, Nislow C, Jaramillo DF, Chu AM, Jordan MI, Arkin AP, Davis RW (2004) Chemogenomic profiling: identifying the functional interactions of small molecules in yeast. Proc Natl Acad Sci U S A 101(3):793–798.  https://doi.org/10.1073/pnas.0307490100CrossRefPubMedPubMedCentralGoogle Scholar
  24. Hammond TG, Allen PL, Gunter MA, Chiang J, Giaever G, Nislow C, Birdsall HH (2017) Physical forces modulate oxidative status and stress defense meditated metabolic adaptation of yeast colonies: spaceflight and microgravity simulations. Microgravity Sci Technol 30:195.  https://doi.org/10.1007/s12217-017-9588-zCrossRefGoogle Scholar
  25. Hamza A, Tammpere E, Kofoed M, Keong C, Chiang J, Giaever G, Nislow C, Hieter P (2015) Complementation of yeast genes with human genes as an experimental platform for functional testing of human genetic variants. Genetics 201(3):1263–1274.  https://doi.org/10.1534/genetics.115.181099CrossRefPubMedPubMedCentralGoogle Scholar
  26. Havugimana PC, Hu P, Emili A (2017) Protein complexes, big data, machine learning and integrative proteomics: lessons learned over a decade of systematic analysis of protein interaction networks. Expert Rev Proteomics 14(10):845–855.  https://doi.org/10.1080/14789450.2017.1374179CrossRefPubMedGoogle Scholar
  27. Hillenmeyer ME, Ericson E, Davis RW, Nislow C, Koller D, Giaever G (2010) Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action. Genome Biol 11(3):R30.  https://doi.org/10.1186/gb-2010-11-3-r30CrossRefPubMedPubMedCentralGoogle Scholar
  28. Hoon S, St Onge RP, Giaever G, Nislow C (2008) Yeast chemical genomics and drug discovery: an update. Trends Pharmacol Sci 29(10):499–504.  https://doi.org/10.1016/j.tips.2008.07.006CrossRefPubMedGoogle Scholar
  29. Jelinsky SA, Estep P, Church GM, Samson LD (2000) Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes. Mol Cell Biol 20(21):8157–8167CrossRefGoogle Scholar
  30. Johanson K, Allen PL, Gonzalez-Villalobos R, Nesbit J, Nickerson CA, Honer zu Bentrup K, Wilson JW, Ramamurthy R, D’Elia R, Muse KE, Freeman J, Stodieck LS, Hammond JS, Hammond TG (2007) Haploid deletion strains of Saccharomyces cerevisiae that determine survival during space flight. Acta Astronaut 60(4–7):460–471CrossRefGoogle Scholar
  31. Kaeberlein M, Burtner CR, Kennedy BK (2007) Recent developments in yeast aging. PLoS Genet 3(5):e84.  https://doi.org/10.1371/journal.pgen.0030084CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kellis M, Patterson N, Endrizzi M, Birren B, Lander ES (2003) Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423(6937):241–254.  https://doi.org/10.1038/nature01644CrossRefPubMedGoogle Scholar
  33. Kiefer J, Pross HD (1999) Space radiation effects and microgravity. Mutat Res 430(2):299–305CrossRefGoogle Scholar
  34. Kumar A, Snyder M (2001) Emerging technologies in yeast genomics. Nat Rev Genet 2(4):302–312.  https://doi.org/10.1038/35066084CrossRefPubMedGoogle Scholar
  35. Lee AY, St Onge RP, Proctor MJ, Wallace IM, Nile AH, Spagnuolo PA, Jitkova Y, Gronda M, Wu Y, Kim MK, Cheung-Ong K, Torres NP, Spear ED, Han MK, Schlecht U, Suresh S, Duby G, Heisler LE, Surendra A, Fung E, Urbanus ML, Gebbia M, Lissina E, Miranda M, Chiang JH, Aparicio AM, Zeghouf M, Davis RW, Cherfils J, Boutry M, Kaiser CA, Cummins CL, Trimble WS, Brown GW, Schimmer AD, Bankaitis VA, Nislow C, Bader GD, Giaever G (2014) Mapping the cellular response to small molecules using chemogenomic fitness signatures. Science 344(6180):208–211.  https://doi.org/10.1126/science.1250217CrossRefPubMedPubMedCentralGoogle Scholar
  36. Najrana T, Sanchez-Esteban J (2016) Mechanotransduction as an adaptation to gravity. Front Pediatr 4(140).  https://doi.org/10.3389/fped.2016.00140
  37. Nislow C, Lee AY, Allen PL, Giaever G, Smith A, Gebbia M, Stodieck LS, Hammond JS, Birdsall HH, Hammond TG (2015) Genes required for survival in microgravity revealed by genome-wide yeast deletion collections cultured during spaceflight. Biomed Res Int 2015:976458.  https://doi.org/10.1155/2015/976458CrossRefPubMedPubMedCentralGoogle Scholar
  38. Pierce SE, Fung EL, Jaramillo DF, Chu AM, Davis RW, Nislow C, Giaever G (2006) A unique and universal molecular barcode array. Nat Methods 3(8):601–603.  https://doi.org/10.1038/nmeth905CrossRefPubMedGoogle Scholar
  39. Pierce SE, Davis RW, Nislow C, Giaever G (2007) Genome-wide analysis of barcoded Saccharomyces cerevisiae gene-deletion mutants in pooled cultures. Nat Protoc 2(11):2958–2974.  https://doi.org/10.1038/nprot.2007.427CrossRefPubMedGoogle Scholar
  40. Purevdorj-Gage B, Sheehan KB, Hyman LE (2006) Effects of low-shear modeled microgravity on cell function, gene expression, and phenotype in Saccharomyces cerevisiae. Appl Environ Microbiol 72(7):4569–4575.  https://doi.org/10.1128/AEM.03050-05CrossRefPubMedPubMedCentralGoogle Scholar
  41. Roemer T, Davies J, Giaever G, Nislow C (2012) Bugs, drugs and chemical genomics. Nat Chem Biol 8(1):46–56.  https://doi.org/10.1038/nchembio.744CrossRefGoogle Scholar
  42. Scannell DR, Butler G, Wolfe KH (2007) Yeast genome evolution―the origin of the species. Yeast 24(11):929–942.  https://doi.org/10.1002/yea.1515CrossRefPubMedGoogle Scholar
  43. Searles SC, Woolley CM, Petersen RA, Hyman LE, Nielsen-Preiss SM (2011) Modeled microgravity increases filamentation, biofilm formation, phenotypic switching, and antimicrobial resistance in Candida albicans. Astrobiology 11(8):825–836.  https://doi.org/10.1089/ast.2011.0664CrossRefPubMedGoogle Scholar
  44. Sheehan KB, McInnerney K, Purevdorj-Gage B, Altenburg SD, Hyman LE (2007) Yeast genomic expression patterns in response to low-shear modeled microgravity. BMC Genomics 8:3.  https://doi.org/10.1186/1471-2164-8-3CrossRefPubMedPubMedCentralGoogle Scholar
  45. Sherlock G (2000) Analysis of large-scale gene expression data. Curr Opin Immunol 12(2):201–205CrossRefGoogle Scholar
  46. Shoemaker DD, Lashkari DA, Morris D, Mittmann M, Davis RW (1996) Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar-coding strategy. Nat Genet 14(4):450–456.  https://doi.org/10.1038/ng1296-450CrossRefPubMedGoogle Scholar
  47. Sinha S, Flibotte S, Neira M, Formby S, Plemenitas A, Cimerman NG, Lenassi M, Gostincar C, Stajich JE, Nislow C (2017) Insight into the recent genome duplication of the halophilic yeast Hortaea werneckii: combining an improved genome with gene expression and chromatin structure. G3 (Bethesda) 7(7):2015–2022.  https://doi.org/10.1534/g3.117.040691CrossRefGoogle Scholar
  48. Smith AM, Ammar R, Nislow C, Giaever G (2010) A survey of yeast genomic assays for drug and target discovery. Pharmacol Ther 127(2):156–164.  https://doi.org/10.1016/j.pharmthera.2010.04.012CrossRefPubMedPubMedCentralGoogle Scholar
  49. Smith AM, Durbic T, Kittanakom S, Giaever G, Nislow C (2012) Barcode sequencing for understanding drug-gene interactions. Methods Mol Biol 910:55–69.  https://doi.org/10.1007/978-1-61779-965-5_4CrossRefPubMedGoogle Scholar
  50. Takahashi A, Ohnishi K, Takahashi S, Masukawa M, Sekikawa K, Amano T, Nakano T, Nagaoka S, Ohnishi T (2001) The effects of microgravity on induced mutation in Escherichia coli and Saccharomyces cerevisiae. Adv Space Res 28(4):555–561CrossRefGoogle Scholar
  51. Todd P (2004) Overview of the spaceflight radiation environment and its impact on cell biology experiments. J Gravit Physiol 11(1):11–16PubMedGoogle Scholar
  52. Ulitsky I, Maron-Katz A, Shavit S, Sagir D, Linhart C, Elkon R, Tanay A, Sharan R, Shiloh Y, Shamir R (2010) Expander: from expression microarrays to networks and functions. Nat Protoc 5(2):303–322.  https://doi.org/10.1038/nprot.2009.230CrossRefPubMedGoogle Scholar
  53. Wach A, Brachat A, Pohlmann R, Philippsen P (1994) New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 10(13):1793–1808CrossRefGoogle Scholar
  54. Walther I, Bechler B, Muller O, Hunzinger E, Cogoli A (1996) Cultivation of Saccharomyces cerevisiae in a bioreactor in microgravity. J Biotechnol 47(2–3):113–127CrossRefGoogle Scholar
  55. Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, Bangham R, Benito R, Boeke JD, Bussey H, Chu AM, Connelly C, Davis K, Dietrich F, Dow SW, El Bakkoury M, Foury F, Friend SH, Gentalen E, Giaever G, Hegemann JH, Jones T, Laub M, Liao H, Liebundguth N, Lockhart DJ, Lucau-Danila A, Lussier M, M’Rabet N, Menard P, Mittmann M, Pai C, Rebischung C, Revuelta JL, Riles L, Roberts CJ, Ross-MacDonald P, Scherens B, Snyder M, Sookhai-Mahadeo S, Storms RK, Veronneau S, Voet M, Volckaert G, Ward TR, Wysocki R, Yen GS, Yu K, Zimmermann K, Philippsen P, Johnston M, Davis RW (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285(5429):901–906CrossRefGoogle Scholar
  56. Wong LH, Sinha S, Bergeron JR, Mellor JC, Giaever G, Flaherty P, Nislow C (2016) Reverse chemical genetics: comprehensive fitness profiling reveals the Spectrum of drug target interactions. PLoS Genet 12(9):e1006275.  https://doi.org/10.1371/journal.pgen.1006275CrossRefPubMedPubMedCentralGoogle Scholar
  57. Yan Z, Costanzo M, Heisler LE, Paw J, Kaper F, Andrews BJ, Boone C, Giaever G, Nislow C (2008) Yeast Barcoders: a chemogenomic application of a universal donor-strain collection carrying bar-code identifiers. Nat Methods 5(8):719–725.  https://doi.org/10.1038/nmeth.1231CrossRefPubMedGoogle Scholar
  58. Zimmermann A, Kainz K, Andryushkova A, Hofer S, Madeo F, Carmona-Gutierrez D (2016) Autophagy: one more Nobel Prize for yeast. Microb Cell 3(12):579–581.  https://doi.org/10.15698/mic2016.12.544CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Durham Veterans Affairs Medical CenterDurhamUSA
  2. 2.Nephrology Division, Department of MedicineDuke University School of MedicineDurhamUSA
  3. 3.Space Policy Institute, Elliot School of International AffairsGeorge Washington UniversityWashingtonUSA
  4. 4.Office of Research and DevelopmentDepartment of Veterans AffairsWashingtonUSA
  5. 5.Departments of Otolaryngology, Immunology, and PsychiatryBaylor College of MedicineHoustonUSA

Section editors and affiliations

  • Luis Zea
    • 1
  1. 1.BioServe Space TechnologiesUniversity of ColoradoBoulderUSA

Personalised recommendations