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Project Title:  Investigating Lunar Stress and Parkinson's Disease Using an Alpha Synuclein Yeast Model Reduce
Images: icon  Fiscal Year: FY 2024 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Microbiology  
Start Date: 12/01/2021  
End Date: 07/30/2024  
Task Last Updated: 01/02/2024 
Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Robinson, Lucy  Ph.D. / Louisiana State University System 
Address:  Biochemistry and Molecular Biology 
1501 Kings Hwy  
Shreveport , LA 71130 
Email: lucy.robinson@lsuhs.edu 
Phone: 318-675-5164  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Louisiana State University System 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Shi, Runhua  Ph.D. Louisiana State University System  
Tatchell, Kelly  Ph.D. Louisiana State University System 
Chancellor, Jeffery  Ph.D. Louisiana State University, Baton Rouge 
Key Personnel Changes / Previous PI: NOTE: Per NASA Ames Research Center, the former Principal Investigator (Lynn Harrison, Ph.D., Louisiana State University) has moved to a new position and will no longer serve as PI on this project. A former Co-Investigator on the project will serve as the new PI. The new PI is Lucy Robinson, Ph.D. of Louisiana State University Health Sciences Center at Shreveport. (Ed., 3/7/23)
Project Information: Grant/Contract No. 80NSSC22K0252 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Yuri.V.Griko@nasa.gov 
Unique ID: 15426 
Solicitation / Funding Source: 2021 Space Biology NNH21ZDA001N-LEIA E.10. Lunar Explorer Instrument for Space Biology Applications 
Grant/Contract No.: 80NSSC22K0252 
Project Type: GROUND 
Flight Program:  
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Space Biology Element: (1) Cell & Molecular Biology
(2) Microbiology
Space Biology Cross-Element Discipline: (1) Neurobiology
Space Biology Special Category: None
Flight Assignment/Project Notes: NOTE: End date changed to 07/30/2024 per NSSC information (Ed., 1/4/24).

Task Description: Astronauts will be exposed to partial gravity and deep space high energy radiation when living on the surface of the moon. Ionizing radiation increases oxidative stress in cells, and persistent oxidative stress in neurons from repeated exposure to low dose high energy radiation could increase the risk of developing neurodegenerative disease. Experiments are therefore needed to determine whether lunar living conditions increase toxic forms of proteins known to be involved in neurodegeneration. Alpha-synuclein (SYN) and mutations of this protein are implicated in Parkinson’s disease. One such familial mutation is A53T-SYN, which increases aggregate formation and toxicity of SYN. Toxic forms of SYN can also form in cells under oxidative stress. The objective of this proposal is to determine whether lunar radiation or the stress of exposure to one sixth the Earth’s gravity increases the toxicity of SYN.

Two aims are proposed: aim 1 is to test the experiment in the Biosensor hardware to prepare for a possible lunar lander mission in the future and aim 2 is to use ground-based studies to determine whether SYN or A53T-SYN toxicity is increased by simulated lunar radiation or simulated lunar gravity. The Biosensor hardware has been tested for toxicity studies using yeast and the expression of SYN in Saccharomyces cerevisiae is an established model of Parkinson’s disease. Low SYN levels in yeast are not toxic, but high levels induce apoptosis and Reactive Oxidative Species (ROS) accumulation. We will generate wild-type and RAD51 deleted Saccharomyces cerevisiae strains that can be induced to express SYN or A53T-SYN at low levels by red light. RAD51 deleted yeast are more radiosensitive than wild-type yeast and will increase the sensitivity of detection of SYN toxicity generated by radiation/oxidative stress exposure. Genes known to reduce SYN toxicity in yeast include the gene encoding manganese superoxide dismutase (SOD2), an enzyme that detoxifies superoxide radicals in mitochondria. We will therefore also develop strains that overexpress SOD2 in combination with SYN to determine whether SYN toxicity can be rescued by quenching superoxide radicals. The Biosensor hardware can determine toxicity by the Alamar Blue viability assay, and growth by culture turbidity. We will use these assays in aims 1 and 2 to determine SYN toxicity as well as colony-forming ability in the ground-based studies in aim 2. In aim 2, simulated lunar gravity will be achieved using the random positioning machine (RPM 2.0) at Kennedy Space Center and simulated lunar radiation exposure will be performed at Brookhaven. Dr. Chancellor, a team member, has developed techniques to recreate the polyenergetic radiation spectrum for ground-based studies of galactic cosmic rays, and will use measurements scheduled to occur in early 2022 on the lunar surface to guide exposure of the cultures at Brookhaven in aim 2.

From the work in this proposal, we will be able to study SYN toxicity. We hypothesize that expressing SYN or A53T-SYN in yeast will increase toxicity to simulated lunar radiation or simulated lunar gravity, and toxicity will be greater in yeast expressing A53T-SYN. Toxicity will be decreased by overexpressing SOD2, an enzyme known to protect against SYN toxicity. Understanding how the stresses of living on the moon can enhance SYN toxicity is significant to humans thriving in deep space as extended space missions on the moon could enhance neurodegeneration in astronauts. Knowing the risks will allow NASA to establish countermeasures to protect astronauts on future deep space missions.

Research Impact/Earth Benefits: This will be the first time that a yeast model of Parkinson's disease will be used to study the effect of lunar gravity and the lunar radiation environment on aggregation of a protein implicated in Parkinson's disease. This could have implications for risk assessment of neurodegeneration for astronauts living on the Moon. These experiments will provide the ground-based studies needed to justify performing experiments on the Moon. They will open up this field of research to other space biologists so the risk of neurodegeneration can be assessed in animals on the Moon. Without knowing how lunar living stress conditions alter brain physiology, it is not possible to design necessary countermeasures to keep our astronauts safe. Understanding the effects of alpha synuclein on irradiated cells will also have implications for radiotherapy patients that receive radiation to the brain. Experiments include initial tests with gamma radiation.

Task Progress & Bibliography Information FY2024 
Task Progress: Astronauts are exposed to harmful conditions in space, particularly radiation from the sun and cosmic rays and partial gravity. Ionizing radiation removes electrons from water molecules, resulting in oxidizing conditions harmful to protein, fat, and DNA integrity. Depending on the astronaut’s genetic makeup, they can be more or less sensitive to these harmful conditions. For example, Parkinson's disease risk can increase due to exposure to agents that are known to cause oxidizing conditions in human cells, as well as to genetic changes in a particular protein, synuclein. Therefore, we are interested in exploring a relationship between synuclein and the oxidizing effects of radiation.

Budding yeast (brewer’s or baker’s yeast) is often used as a model to study basic mechanisms that also operate in human cells, because many basic cell processes are the same, but genetic modification and analysis are straightforward and rapid. We are preparing to test whether specific alterations to the yeast genetic makeup make them more or less sensitive to radiation-induced oxidizing conditions. The Parkinson's-related protein, synuclein, is normally present in human cells, but not yeast cells. We have used recombinant DNA methods to alter the yeast to synthesize this protein under conditions we impose. During this year of the project, we constructed a set of genetically modified yeast that will allow us to ask two questions:

-Does the presence of synuclein increase sensitivity to (death from) radiation?

-Do increased levels of a conserved antioxidant protein protect cells (with or without synuclein protein) from radiation effects?

We had, in the previous year, made a set of strains for this purpose, but found that these yeast strains were unable to survive the drying process needed to eventually be tested in lunar or space conditions. Therefore, we identified a better genetic makeup for this purpose and recreated our set of strains using this genetic makeup. Our testing is upcoming for visualizing yeast synthesis of synuclein, as well as testing the effects on radiation survival of making this protein.

Bibliography: Description: (Last Updated: ) 

Show Cumulative Bibliography
 
 None in FY 2024
Project Title:  Investigating Lunar Stress and Parkinson's Disease Using an Alpha Synuclein Yeast Model Reduce
Images: icon  Fiscal Year: FY 2023 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Microbiology  
Start Date: 12/01/2021  
End Date: 11/30/2023  
Task Last Updated: 03/07/2023 
Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Robinson, Lucy  Ph.D. / Louisiana State University System 
Address:  Biochemistry and Molecular Biology 
1501 Kings Hwy  
Shreveport , LA 71130 
Email: lucy.robinson@lsuhs.edu 
Phone: 318-675-5164  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Louisiana State University System 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Shi, Runhua  Ph.D. Louisiana State University System  
Tatchell, Kelly  Ph.D. Louisiana State University System 
Chancellor, Jeffery  Ph.D. Louisiana State University, Baton Rouge 
Key Personnel Changes / Previous PI: NOTE: Per NASA Ames Research Center, the former Principal Investigator (Lynn Harrison, Ph.D., Louisiana State University) has moved to a new position and will no longer serve as PI on this project. A former CoInvestigator on the project will serve as the new PI. The new PI is Lucy Robinson, Ph.D. of Louisiana State University. (Ed., 3/7/23)
Project Information: Grant/Contract No. 80NSSC22K0252 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Yuri.V.Griko@nasa.gov 
Unique ID: 15426 
Solicitation / Funding Source: 2021 Space Biology NNH21ZDA001N-LEIA E.10. Lunar Explorer Instrument for Space Biology Applications 
Grant/Contract No.: 80NSSC22K0252 
Project Type: GROUND 
Flight Program:  
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Cell & Molecular Biology
(2) Microbiology
Space Biology Cross-Element Discipline: (1) Neurobiology
Space Biology Special Category: None
Task Description: Astronauts will be exposed to partial gravity and deep space high energy radiation when living on the surface of the moon. Ionizing radiation increases oxidative stress in cells, and persistent oxidative stress in neurons from repeated exposure to low dose high energy radiation could increase the risk of developing neurodegenerative disease. Experiments are therefore needed to determine whether lunar living conditions increase toxic forms of proteins known to be involved in neurodegeneration. Alpha-synuclein (SYN) and mutations of this protein are implicated in Parkinson’s disease. One such familial mutation is A53T-SYN, which increases aggregate formation and toxicity of SYN. Toxic forms of SYN can also form in cells under oxidative stress. The objective of this proposal is to determine whether lunar radiation or the stress of exposure to one sixth the Earth’s gravity increases the toxicity of SYN.

Two aims are proposed: aim 1 is to test the experiment in the Biosensor hardware to prepare for a possible lunar lander mission in the future and aim 2 is to use ground-based studies to determine whether SYN or A53T-SYN toxicity is increased by simulated lunar radiation or simulated lunar gravity. The Biosensor hardware has been tested for toxicity studies using yeast and the expression of SYN in Saccharomyces cerevisiae is an established model of Parkinson’s disease. Low SYN levels in yeast are not toxic, but high levels induce apoptosis and Reactive Oxidative Species (ROS) accumulation. We will generate wild-type and RAD51 deleted Saccharomyces cerevisiae strains that can be induced to express SYN or A53T-SYN at low levels by red light. RAD51 deleted yeast are more radiosensitive than wild-type yeast and will increase the sensitivity of detection of SYN toxicity generated by radiation/oxidative stress exposure. Genes known to reduce SYN toxicity in yeast include the gene encoding manganese superoxide dismutase (SOD2), an enzyme that detoxifies superoxide radicals in mitochondria. We will therefore also develop strains that overexpress SOD2 in combination with SYN to determine whether SYN toxicity can be rescued by quenching superoxide radicals. The Biosensor hardware can determine toxicity by the Alamar Blue viability assay, and growth by culture turbidity. We will use these assays in aims 1 and 2 to determine SYN toxicity as well as colony-forming ability in the ground-based studies in aim 2. In aim 2, simulated lunar gravity will be achieved using the random positioning machine (RPM 2.0) at Kennedy Space Center and simulated lunar radiation exposure will be performed at Brookhaven. Dr. Chancellor, a team member, has developed techniques to recreate the polyenergetic radiation spectrum for ground-based studies of galactic cosmic rays, and will use measurements scheduled to occur in early 2022 on the lunar surface to guide exposure of the cultures at Brookhaven in aim 2.

From the work in this proposal, we will be able to study SYN toxicity. We hypothesize that expressing SYN or A53T-SYN in yeast will increase toxicity to simulated lunar radiation or simulated lunar gravity, and toxicity will be greater in yeast expressing A53T-SYN. Toxicity will be decreased by overexpressing SOD2, an enzyme known to protect against SYN toxicity. Understanding how the stresses of living on the moon can enhance SYN toxicity is significant to humans thriving in deep space as extended space missions on the moon could enhance neurodegeneration in astronauts. Knowing the risks will allow NASA to establish countermeasures to protect astronauts on future deep space missions.

Research Impact/Earth Benefits: This will be the first time that a yeast model of Parkinson's disease will be used to study the effect of lunar gravity and the lunar radiation environment on aggregation of a protein implicated in Parkinson's disease. This could have implications for risk assessment of neurodegeneration for astronauts living on the Moon. These experiments will provide the ground-based studies needed to justify performing experiments on the Moon. They will open up this field of research to other space biologists so the risk of neurodegeneration can be assessed in animals on the Moon. Without knowing how lunar living stress conditions alter brain physiology, it is not possible to design necessary countermeasures to keep our astronauts safe. Understanding the effects of alpha synuclein on irradiated cells will also have implications for radiotherapy patients that receive radiation to the brain. Experiments include initial tests with gamma radiation.

Task Progress & Bibliography Information FY2023 
Task Progress: New Project for FY2023.

Bibliography: Description: (Last Updated: ) 

Show Cumulative Bibliography
 
 None in FY 2023