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Project Title:  Effect of Altered Gravity on the Nucleus Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology  
Start Date: 02/01/2020  
End Date: 01/31/2021  
Task Last Updated: 03/23/2020 
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Principal Investigator/Affiliation:   Neelam, Srujana  Ph.D. / University of Wisconsin-Madison 
Address:  College of Letters and Science 
Birge Hall, 430 Lincoln Dr 
Madison , WI 53706 
Congressional District:
Organization Type: UNIVERSITY 
Organization Name: University of Wisconsin-Madison 
Joint Agency:  
Ullrich, Oliver  M.D., Ph.D. Universitat Zurich, Switzerland 
Lele, Tanmay  Ph.D. University of Florida, Gainesville 
Project Information: Grant/Contract No. 80NSSC20K0423 
Responsible Center: NASA KSC 
Grant Monitor: Zhang, Ye  
Center Contact: 321-861-3253 
Solicitation: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-MS, PS, AB. App D,E,F: Research Using Microgravity Simulation Devices, Parabolic and Suborbital Flights, and Antarctic Balloons 
Grant/Contract No.: 80NSSC20K0423 
Project Type: GROUND 
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Space Biology Element: (1) Cell & Molecular Biology
Space Biology Cross-Element Discipline: None
Space Biology Special Category: (1) Cell Culture
Task Description: Altered gravity is known to influence various cell functions like cell proliferation, signal transduction, and gene expression, in addition to the changes in cell morphology, focal adhesion, and cytoskeletal organization across a wide range of cell types. Such wide range of phenotypic changes in altered gravity is linked to various abnormalities observed in astronauts returning from space but the biological mechanisms resulting in these changes are not yet understood. Our preliminary results suggest that simulated microgravity significantly alters nuclear morphology. Changes in nuclear shape can alter gene expression because the nucleus houses the genome, and changes in nuclear shape can alter chromatin conformation. Therefore, we propose to understand the mechanisms by which true altered gravity impacts nuclear morphology. Our hypothesis is that the LINC (Linker of Nucleoskeleton to Cytoskeleton) complex, a nuclear envelope complex which links the cytoskeleton to the nucleus, is sensitive to altered gravity mediated effects on the nuclear structure, nuclear tension, and subsequently on gene expression.

We propose to identify the effects of altered gravity on nuclear morphology and cytoskeletal organization in fibroblasts flown in parabolic flight. Cells flown will be cultured in a specially designed hardware to control for temperature and humidity, and the cells will be fixed on flight at different timepoints. High resolution imaging of cell shape and nuclear shape will be carried out using a laser scanning confocal microscope. Image analysis software will be used for three- dimensional shape reconstruction and quantification of shape parameters. We will characterize the mechanical forces acting on the nucleus using a Fluorescence Resonance Energy Transfer (FRET) probe biosensor to investigate the effect of altered gravity on the nuclear tension. Finally, we will identify the genes that are differentially expressed in LINC disrupted cells to understand the mechanotransduction pathway in sensing altered gravity.

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Task Progress & Bibliography Information FY2020 
Task Progress: New project for FY2020.

Bibliography Type: Description: (Last Updated: )  Show Cumulative Bibliography Listing
 None in FY 2020