Project start: May, 2019
Expected launch around the Moon (NASA's Artemis 1 mission): September, 2020
Expected launch to ISS: 2021
Humans will once again venture to the Moon and eventually, beyond. While the region of space where the International Space Station orbits is partially protected from space radiation by our planet’s magnetosphere, astronauts going to the Moon will be exposed to higher doses of galactic cosmic rays and solar radiation. Because neither humans, or for that matter, any terrestrial life forms have experienced long-term exposure these environments, we don’t yet fully understand how such radiation affects biological systems. For example, it is crucial to be able to address:
- What level and kind of damage can we expect to cells and their DNA as a result of these types of radiation?
- What are the biological processes that improve cells’ ability to thrive under conditions of microgravity and space radiation?
- Which DNA repair mechanisms are most effective under these conditions?
What are this project's objectives?
The overarching aim of this project is to identify the metabolic and genomic pathways affected by microgravity, space radiation, and a combination thereof. These observations will then be used to inform pathway-specific and gene-specific approaches designed to ameliorate the detrimental effects of long-term radiation exposure.
How is this being done?
Because it is prohibitive to study most organisms with a sufficiently large sample size and for a sufficient number of generations, especially for humans, model organisms can be used as powerful proxies to understand such fundamental gene × environment questions. By selecting a model organism that shares many of the key, evolutionarily conserved aspects being studied, one can use large populations of model organisms, with well characterized genomes, to refine human tests which can be addressed with small, focused studies. In this case, we will use yeast, because 70% of its essential genes have a human homolog (i.e. they are also found on the human genetic code), and over half of these homologs can functionally replace their human counterpart. More specifically, this project will use a molecularly barcoded yeast genome-wide knockdown collection, a set of systematically engineered strains each deleted for a single gene) that will enable the systematic interrogation of the effect of microgravity, space radiation, and a combination thereof in each gene.
To differentiate the effects of microgravity and space radiation on each strain, an experimental set of all mutants will be flown beyond the van Allen belts on Orion’s Artemis 1 Mission (considered in microgravity and irradiated by space radiation) and equivalent sets will be cultured asynchronously on board the International Space Station (ISS) (considered in microgravity but mostly – although not completely – protected of space radiation by the van Allen Belts), and on Earth. The experiment will have a controlled-start once the spacecraft has past Earth’s magnetosphere on its way to the Moon, and will be conducted in the Peristaltic Laboratory for Automated Science with Multigenerations (PLASM) spaceflight hardware.
Our team is composed of scientists, engineers, and undergraduate and graduate students from two national space agencies (NASA, German Aerospace Center (DLR)), four universities (University of British Columbia, University of Colorado, Boulder, the Massachusetts Institute of Technology (MIT), and Universidad del Valle de Guatemala (UVG)), and two research centers (Sequencing and Bioinformatics Consortium and BioServe Space Technologies). The team is located in four countries around the globe: United States, Canada, Germany, and Guatemala.
Principal Investigators: Luis Zea, Ph.D. and Corey Nislow, Ph.D.
Co-Investigator: Louis Stodieck, Ph.D.
Collaborators: Ralf Möller, Ph.D., Christopher Carr, Ph.D., and Tobias Niederwieser, Ph.D.
Engineering Team: Alex Hoehn, Ph.D., Jim Wright, Gary Stanish, Mike Grusin, and Sam Piper
The students at the University of British Columbia, University of Colorado, Boulder (BioServe), Universidad del Valle de Guatemala (UVG), DLR, and MIT are the backbone of this project.
Samantha Breaux - Sam received her BSc in Microbiology at the University of Washington in 2017. Since starting her graduate program at UBC in 2018, Sam has been involved in a wide array of genomic projects, including; nanopore sequence to track Cystic Fibrosis bacterial outbreaks, training Pharmacists to interpret pharmacogenomic data and designing environmental selections and high-throughput screening to improve yeast ethanol and fuel production. Sam is involved in all aspects of the wet lab components of the yeast project.
Students from the rest of the team’s institutions will join as the project continues its development.
DLR announcement: https://www.dlr.de/me/en/desktopdefault.aspx/tabid-1752/2384_read-54339
Further reading on the yeast collections
- Hamza A, Tammpere E, Kofoed M, Keong C, Chiang J, Giaever G, Nislow C, Hieter P. Complementation of Yeast Genes with Human Genes as an Experimental Platform for Functional Testing of Human Genetic Variants. Genetics. 2015 PMID: 26354769;
- Nislow C, Lee AY, Allen PL, Giaever G, Smith A, Gebbia M, Stodieck LS, Hammond JS, Birdsall HH, Hammond TG. Genes required for survival in microgravity revealed by genome-wide yeast deletion collections cultured during spaceflight. Biomed Res Int. 2015;2015:976458. PMID:25667933
- Giaever G, Nislow C. The yeast deletion collection: a decade of functional genomics. Genetics. 2014 Jun;197(2):451-65. 2014 Jun 17. PMID: 24939991
- Douglas AC, Smith AM, Sharifpoor S, Yan Z, Durbic T, Heisler LE, Lee AY, Ryan O, Göttert H, Surendra A, van Dyk D, Giaever G, Boone C, Nislow C, Andrews BJ. Functional analysis with a barcoder yeast gene overexpression system. G3
- 2012 PMID: 23050238
- Smith AM, Durbic T, Oh J, Urbanus M, Proctor M, Heisler LE, Giaever G, Nislow C. Competitive genomic screens of barcoded yeast libraries. J Vis Exp. 2011 Aug 11;(54). PMID: 21860376
- Hillenmeyer ME, Fung E, Wildenhain J, Pierce SE, Hoon S, Lee W, Proctor M, St Onge RP, Tyers M, Koller D, Altman RB, Davis RW, Nislow C, Giaever G. The chemical genomic portrait of yeast: uncovering a phenotype for all genes. Science. 2008 Apr 18;320(5874):362-5. PMID: 18420932;