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EXPERIMENT INFORMATION

Defining Epigenetic Programming During Flight Expeditions In Differentiating Embryonic Stem Cells (NNX12AN09G)
Principal Investigator
Research Area:
Cell and molecular biology
Species Studied
Scientific Name: Homo sapiens Species: Human

Description
OBJECTIVE:
Although scientists can determine the function of every gene, limited methods exist for determining how cells interpret instructions that control gene function. The instructions, (epigenetic marks), encompass chemical modifications added "on top of" DNA that do not cause a genetic mutation. Understanding how diverse patterns of epigenetic marks coordinate the regulation of gene expression is an open question because, although many epigenetic landscapes have been mapped in cell populations, limited strategies have been developed to test and/or understand how epigenetic control occurs in single cells. Epigenetic modifications respond dynamically to environmental factors, and can change within minutes. In space, organisms are exposed to powerful environmental forces (microgravity, cosmic radiation, magnetic fields) that potentially modulate the epigenome, leading to changes in gene expression that affect mammalian development. By elucidating the mechanisms that govern epigenetic programming and gene regulation in single cells, we will provide fundamental knowledge that will broadly impact the epigenetics community, basic biology, and NASA's space biology programs.

The goal of our interdisciplinary effort is to develop an integrated approach comprised of Next Generation Sequencing and single cell microscopy platforms to understand how the space environment affects DNA methylation, hydroxymethylation, and histone modifications to regulate gene expression during differentiation using an Embryonic Stem Cell model.

Through our interdisciplinary effort, we will create a framework to explain how DNA methylation (5hmeC, 5meC) and histone modifications regulate gene expression not only in response to space flight conditions, but also to environments encountered on Earth. Answers to this question, which must be tested in single cells, have heretofore remained elusive. Upon completion, our work will transform the basic biological understanding of epigenetics, propel the current space biology research program into the realm of epigenetics and impact the planning of future long-term space flight expeditions at NASA.


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Publications
Chowdhury B, Seetharam A3, Wang Z, Liu Y, Lossie AC, Thimmapuram J, Irudayaraj J. A study of alterations in DNA epigenetic modifications (5mC and 5hmC) and gene expression influenced by simulated microgravity in human lymphoblastoid cells. PLoS One. 2016 Jan 28;11(1):e0147514. pubmed.gov [DOI]

Chowdhury B, McGovern A, Cui Y, Choudhury SR, Cho IH, Cooper B, Chevassut T, Lossie AC, Irudayaraj J. The hypomethylating agent Decitabine causes a paradoxical increase in 5-hydroxymethylcytosine in human leukemia cells. Sci Rep. 2015 Apr 22;5:9281. pubmed.gov

Data Information
Data Availability
Archive is complete. No data sets are available for this experiment. Please Contact LSDA if you know of available data for this investigation.

Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

Additional Information
Managing NASA Center
Ames Research Center (ARC)
Responsible NASA Representative
Ames Research Center LSDA Level 3
Project Manager: Sylvain Costes
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
2011
Proposal Source
2011 Space Biology NNH11Z