title: Genes required for survival in microgravity revealed by genome-wide yeast deletion collections cultured during spaceflight.
abstract: Spaceflight is a unique environment with profound effects on biological systems including tissue redistribution and musculoskeletal stresses. However, the more subtle biological effects of spaceflight on cells and organisms are difficult to measure in a systematic, unbiased manner. Here we test the utility of the molecularly barcoded yeast deletion collection to provide a quantitative assessment of the effects of microgravity on a model organism. We developed robust hardware to screen, in parallel, the complete collection of ~4800 homozygous and ~5900 heterozygous (including ~1100 single-copy deletions of essential genes) yeast deletion strains, each carrying unique DNA that acts as strain identifiers. We compared strain fitness for the homozygous and heterozygous yeast deletion collections grown in spaceflight and ground, as well as plus and minus hyperosmolar sodium chloride, providing a second additive stressor. The genome-wide sensitivity profiles obtained from these treatments were then queried for their similarity to a compendium of drugs whose effects on the yeast collection have been previously reported. We found that the effects of spaceflight have high concordance with the effects of DNA-damaging agents and changes in redox state, suggesting mechanisms by which spaceflight may negatively affect cell fitness.
authors: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors: Corey
authors: C
authors: Nislow
authors: Donnelly CCBR, University of Toronto, Toronto, ON, Canada M5S 3E1.
authors: Anna Y
authors: AY
authors: Lee
authors: Durham VA Medical Center, Research & Development Service, Durham, NC 27705, USA.
authors: Patricia L
authors: PL
authors: Allen
authors: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors: Guri
authors: G
authors: Giaever
authors: Donnelly CCBR, University of Toronto, Toronto, ON, Canada M5S 3E1.
authors: Andrew
authors: A
authors: Smith
authors: Donnelly CCBR, University of Toronto, Toronto, ON, Canada M5S 3E1.
authors: Marinella
authors: M
authors: Gebbia
authors: Bioserve Space Technologies, University of Colorado, Boulder, CO 80309, USA.
authors: Louis S
authors: LS
authors: Stodieck
authors: The Institute for Medical Research, Durham, NC 27705, USA.
authors: Jeffrey S
authors: JS
authors: Hammond
authors: Department of Veterans Affairs Office of Research and Development, Washington, DC 20420, USA ; Departments of Otorhinolaryngology, Immunology, and Psychiatry, Baylor College of Medicine, Houston, TX 77030, USA.
authors: Holly H
authors: HH
authors: Birdsall
authors: Durham VA Medical Center, Research & Development Service, Durham, NC 27705, USA ; Department of Veterans Affairs Office of Research and Development, Washington, DC 20420, USA ; Nephrology Division, Department of Internal Medicine, Duke University School of Medicine, Durham, NC 27705, USA ; Nephrology Section, Department of Internal Medicine, George Washington University School of Medicine, Washington, DC 20052, USA.
authors: Timothy G
authors: TG
authors: Hammond
mesh_terms: D004271:DNA, Fungal / Q000235:genetics; D005069:Evaluation Studies as Topic; D017384:Sequence Deletion / Q000235:genetics*; D013026:Space Flight / Q000379:methods; D014893:Weightlessness; D015003:Yeasts / Q000235:genetics* / Q000502:physiology*
chemical_list: D004271:DNA, Fungal