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Project Title:  Mining Biology's Extremes for New Space Radiation Resistance Strategies Reduce
Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
TRISH--TRISH 
Start Date: 10/01/2017  
End Date: 12/31/2020  
Task Last Updated: 07/22/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Fox, Donald  Ph.D. / Duke University Medical Center 
Address:  Pharmacology & Cancer Center 
DUMC Box 3813, C318 LSRC 
Durham , NC 27710 
Email: don.fox@duke.edu 
Phone: 919-613-8756  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Duke University Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kirsch, David  M.D., Ph.D. Duke University Medical Center 
Project Information: Grant/Contract No. NNX16AO69A-T0108 
Responsible Center: TRISH 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2017 HERO NNJ16ZSA001N-TRIRT. Appendix C: Translational Research Institute for Space Health (TRISH) Research Topics 
Grant/Contract No.: NNX16AO69A-T0108 
Project Type: GROUND 
Flight Program:  
TechPort: No 
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:
Human Research Program Elements: None
Human Research Program Risks: None
Human Research Program Gaps: None
Flight Assignment/Project Notes: NOTE: End date changed to 12/31/2020 per TRISH (Ed., 6/17/2020)

Task Description: The purpose of this solicitation is to uncover new understanding of how a species withstands space-relevant radiation exposure, using validation and safety efficacy studies in model organisms. Drosophila is specifically mentioned, and we have expertise in study of Drosophila radiation resistance mechanisms (Bretscher and Fox 2016, Dev Cell). As outlined in the solicitation, we will perform genetic manipulation in vivo in flies, targeting potential Tardigrade resilience mechanisms. Finally, the solicitation discusses follow-up work in rodents, which we are well-equipped to do, as Duke co-investigator Dr. Kirsch has prior NASA-funded experience in studying space radiation effects in mice at Brookhaven NASA Space Radiation Laboratory (NSRL).

Reference: Bretscher, H. S. & Fox, D. T. Proliferation of double-strand break-resistant polyploid cells requires Drosophila FANCD2. Dev Cell 37, 444–457 (2016).

Research Impact/Earth Benefits: These transgenic flies described in aim1 of our research report represent a new resource for the study of Tardigrade gene products and their potential impact on the biology of extreme environmental stress resistance, including resistance to radiation. We have identified multiple tardigrade-unique genes as important tools for countermeasure development. Our aim2 findings suggest that expression of the CRL4/CDT2 complex can also play an important role in radioprotection.

Task Progress & Bibliography Information FY2021 
Task Progress: 1. Original project aims/objectives

AIM1- A targeted Drosophila screen of candidate factors from Tardigrades (Ramazzottius varieornatus) that enhance radiation resistance.

AIM2- An unbiased screen for genes that enhance radiation resistance in the Drosophila hindgut.

2. Key findings

Aim 1- After year 3, we completed our generation of 98 transgenic fly lines to test candidate radioprotector Tardigrade genes. We have now conducted replicated tests of survival after X-ray irradiation (low-linear energy transfer (LET)), as well as after 56Fe irradiation (high LET) for over 70 lines. From these studies, a recurrent theme is that specific Tardigrade superoxide dismutase (SOD) genes are promising radioprotectors. Most excitingly, we found one tardigrade SOD that acts as a radioprotector for both high and low LET radiation, and is superior to its fly counterpart in terms of radioprotection in a fly. Further, we have preliminary evidence that the same top SOD radioprotector found in our fly studies also acts as a novel and potent radioprotector in human cells.

Aim2- After year 3, we screened ~1300 lethal mutant stocks for our proposed unbiased screen. This resulted in the identification of the CRL4/CDT2 complex as an important regulator of radioprotection in fly papillar cells.

3. Impact of key findings on original objectives

Both aims were successful in identifying radioprotectors in flies. A second goal of both aims was to carry these studies forward into mammalian cells. To this end, we have generated cell lines for top-performing radioprotectors from Aim1, and irradiated these lines using high LET radiation (56Fe) at Brookhaven NASA Space Radiation Laboratory (NSRL). Results are not available yet at the time of this progress report, but we are close to achieving the stated goal of the original proposal.

4. Plan for the coming year

Our funding for this project has ended. Our goal is to finalize our studies and publish them in 2021. Our current studies in mammalian cells will be valuable in terms of seeking additional NASA support and for further development of our findings into countermeasures that could be made available to astronauts in the future.

Bibliography Type: Description: (Last Updated: 01/15/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2021
Project Title:  Mining Biology's Extremes for New Space Radiation Resistance Strategies Reduce
Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
TRISH--TRISH 
Start Date: 10/01/2017  
End Date: 12/31/2020  
Task Last Updated: 05/15/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Fox, Donald  Ph.D. / Duke University Medical Center 
Address:  Pharmacology & Cancer Center 
DUMC Box 3813, C318 LSRC 
Durham , NC 27710 
Email: don.fox@duke.edu 
Phone: 919-613-8756  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Duke University Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kirsch, David  M.D., Ph.D. Duke University Medical Center 
Project Information: Grant/Contract No. NNX16AO69A-T0108 
Responsible Center: TRISH 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2017 HERO NNJ16ZSA001N-TRIRT. Appendix C: Translational Research Institute for Space Health (TRISH) Research Topics 
Grant/Contract No.: NNX16AO69A-T0108 
Project Type: GROUND 
Flight Program:  
TechPort: No 
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:
Human Research Program Elements: None
Human Research Program Risks: None
Human Research Program Gaps: None
Flight Assignment/Project Notes: NOTE: End date changed to 12/31/2020 per TRISH (Ed., 6/17/2020)

Task Description: The purpose of this solicitation is to uncover new understanding of how a species withstands space-relevant radiation exposure, using validation and safety efficacy studies in model organisms. Drosophila is specifically mentioned, and we have expertise in study of Drosophila radiation resistance mechanisms (Bretscher and Fox 2016, Dev Cell). As outlined in the solicitation, we will perform genetic manipulation in vivo in flies, targeting potential Tardigrade resilience mechanisms. Finally, the solicitation discusses follow-up work in rodents, which we are well-equipped to do, as Duke co-investigator Dr. Kirsch has prior NASA-funded experience in studying space radiation effects in mice at Brookhaven NASA Space Radiation Laboratory (NSRL).

Reference: Bretscher, H. S. & Fox, D. T. Proliferation of double-strand break-resistant polyploid cells requires Drosophila FANCD2. Dev Cell 37, 444–457 (2016).

Research Impact/Earth Benefits: After year 2 of our proposal we have established 55 Fruit Fly lines expressing individual Tardigrade genes. These transgenic flies represent a new resource for the study of Tardigrade gene products and their potential impact on the biology of extreme environmental stress resistance, including resistance to radiation.

Task Progress & Bibliography Information FY2020 
Task Progress: [Ed. note May 2020: Report submitted by TRISH to Task Book in March 2020; covers reporting as of August 2019.]

Results AIM1-- As outlined in our proposal, we aim to identify single Tardigrade genes that, when expressed in another organism, confer increased radiation resistance. We proposed to use Drosophila to rapidly screen through single Tardigrade genes in a whole organism context. In year two, we screened 47 independent transgenic fly lines for increased resistance to X-ray or 56Fe radiation. Each transgenic line expressed a single Tardigrade gene. Based on lifespan analysis over a 20 day period, ~15% of these lines exhibit at least a 25% reduction in baseline survival relative to isogenic controls, 75% of lines showed a 1-24% reduction in baseline survival, while 10% lines showed a potentially mild improvement in survival. We subjected each line to a survival analysis following a single dose of radiation, and we also included isogenic controls in each radiation experiment. A minimum of 50 animals were scored/radiation trial. Based on dose response studies performed in years 1 and 2 (X-ray studies at Duke and 56Fe studies at NASA Space Radiation Laboratory (NSRL)), we established 15 Gy for both radiation sources as a dose that reproducibly leads to about 50% lethality in 20 day old adults when animals are irradiated during the third larval instar. Of the lines examined so far, 4 show promising effects in terms of increased radiation resistance for at least one radiation source. Each of these lines resulted in approximately a 20% increase in survival relative to isogenic control lines, and for X-ray these candidate radioprotectors showed similar improvement in animal survival in two replicate trials. All 4 lines express genes related to superoxide dismutase (SOD) biology. The same SOD genes identified so far as radioprotective are not the same between X-ray and 56Fe, which could preliminarily suggest differences between protective responses to terrestrial and galactic cosmic radiation. While survival of candidate radioprotective line D2-2 suggests this line may cause a decrease in organismal health in the absence of radiation, the other three candidate radioprotective lines show no significant decrease in fitness, with line F3-2 showing a potentially mild increase in fitness. In the coming year we see no issues with meeting our proposal's stated goal of establishing ~100 transgenic lines, each expressing a Tardigrade-unique gene, and testing each line's ability to confer increased organismal health following X-ray and 56Fe radiation. We anticipate having at least one analysis of each transgenic line for 56Fe following our November 13th, 2019 irradiation at NSRL, and plan an additional NSRL radiation for further replicate analyses in Spring of 2020. At that time, we also plan to subject several lines to 16O radiation, to examine the effect of expressing Tardigrade genes on a second source of galactic cosmic radiation. In the coming year, we are also interested in performing further analyses to determine whether these Tardigrade genes are better than Drosophila SOD genes at conferring radiation resistance, or whether they might synergize with expression of Drosophila SOD genes to improve radiation resistance. Additionally, our collaborators in the Kirsch lab will express our four top candidates in mammalian cells to determine if they observe a similar heightened radiation resistance.

AIM2- As outlined in our proposal, we plan to conduct an unbiased screen for genes that are required for DNA damage resistance in the Drosophila hindgut. In years 1 and 2, we established 1300 independent lines carrying recessive lethal mutations on the X-chromosome. We are maintaining these lines as heterozygotes, but the lines are in a background that permits site-specific recombination on the X-chromosome to yield homozygous mutant hindgut cells. In year two, we encountered issues generating homozygous mutant hindgut cells while also expressing the I-Cre enzyme, which is the source of DNA damage in this screen. This is likely due to the use of repeated heat shocks in our screen. We perform one heat shock at the first larval instar stage to induce homozygous mutant tissue and a second heat shock at the second larval instar stage to activate the I-Cre enzyme at the desired timeframe, which is based on our previously published work (Bretscher and Fox, 2016). To resolve this technical hurdle, in year 2 we have developed a new fly line that lets us induce homozygous mutant cells using a non heat-shock method (the Gal4/UAS system). Based on our preliminary tests with this line, we now appear to have generated all of the fly lines needed to conduct the Aim2 screen within the next 6-8 months.

Reference: Bretscher, H. S. & Fox, D. T. Proliferation of double-strand break-resistant polyploid cells requires Drosophila FANCD2. Dev Cell 37, 444–457 (2016).

Bibliography Type: Description: (Last Updated: 01/15/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2020
Project Title:  Mining Biology's Extremes for New Space Radiation Resistance Strategies Reduce
Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
TRISH--TRISH 
Start Date: 10/01/2017  
End Date: 09/30/2020  
Task Last Updated: 01/15/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Fox, Donald  Ph.D. / Duke University Medical Center 
Address:  Pharmacology & Cancer Center 
DUMC Box 3813, C318 LSRC 
Durham , NC 27710 
Email: don.fox@duke.edu 
Phone: 919-613-8756  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Duke University Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kirsch, David  M.D., Ph.D. Duke University Medical Center 
Project Information: Grant/Contract No. NNX16AO69A-T0108 
Responsible Center: TRISH 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2017 HERO NNJ16ZSA001N-TRIRT. Appendix C: Translational Research Institute for Space Health (TRISH) Research Topics 
Grant/Contract No.: NNX16AO69A-T0108 
Project Type: GROUND 
Flight Program:  
TechPort: No 
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:  
Human Research Program Elements: None
Human Research Program Risks: None
Human Research Program Gaps: None
Task Description: Using powerful genetic screening in Drosophila and follow-up work in mice, we will identify unique genes and gene expression that enhance space radiation tolerance in vivo. Our approach will identify new, organism-relevant strategies to provide space radiation resistance.

1-Specific Aims

Aim1- A targeted Drosophila screen of candidate factors from Tardigrades (Ramazzottius varieornatus) that enhance radiation resistance.

Aim2- An unbiased screen for genes that enhance radiation resistance in the Drosophila hindgut.

2-Relevance

The purpose of this proposal is to uncover new understanding of how a species withstands space-relevant radiation exposure, using validation and safety efficacy studies in model organisms. Drosophila is specifically mentioned, and we have expertise in study of Drosophila radiation resistance mechanisms (Bretscher and Fox 2016, Dev Cell). We will perform genetic manipulation in vivo in flies, targeting potential Tardigrade resilience mechanisms. Finally, we discuss follow-up work in rodents, which we are well-equipped to do, as Duke co-investigator Dr. Kirsch has prior NASA-funded experience in studying space radiation effects in mice at Brookhaven NASA Space Radiation Laboratory (NSRL).

3-Approach

Aim1- We will generate novel Drosophila strains expressing candidate Tardigrade genes, and assay their effects on resistance to both high charge and energy (HZE) particles (56Fe), and as a comparison, X-ray irradiation. Tardigrades have recently shown promise for finding factors that enhance radiation tolerance (Hashimoto et al., Nat. Comm. 2016). Genome data for this radiation-resistant organism is now available. From our collaborators Bob Goldstein, we will obtain animals for cDNA generation. We will generate up to 165 unique fly lines, each expressing a Tardigrade gene that, relative to Drosophila or humans, is unique (low homology) and/or induced by radiation. Flies will then be subjected to HZE particles at NSRL or X-irradiation at Duke, and monitored for long-term survival, multi-generational fecundity, and will be sequenced at distinct generations to quantify radiation-induced mutations. Genes with promising enhanced radiation resistance will be pursued further in transgenic mice subjected to similar tests as in flies.

Aim2- Relative to candidate screens (Aim1), un-biased fly screens are more applicable to genome-wide study. The Fox laboratory recently identified a Drosophila cell type (hindgut papillar cells) that is highly resistant to X-irradiation, and used a simple in vivo candidate screen to find genes required for the heightened radiation resistance. Expanding on this successful strategy, we will screen 1/5 of the entire genome through ethyl methanesulfonate (EMS) mutagenesis. Mutant strains will be assayed for DNA damage resistance in hindgut papillar cells. Interesting mutants will be sequenced to find causative genes. We will then generate transgenic flies expressing genes that mediate radiation resistance throughout the fly, and perform tests of HZE particle and X-irradiation resistance, including long-term organismal assays and follow-up mouse experiments as in Aim1.

4-Impact and 5-Rationale for mitigating space exploration risks

Space radiation poses a significant threat to astronaut health, and novel approaches are needed to limit space radiation damage. Drosophila and mice provide convenient, in vivo-relevant screening platforms, and effects on organism health, such as fecundity, can be scored. Understanding mechanisms that prevent space radiation damage in model organisms may uncover new space radiation resistance strategies to be targeted in humans. Such strategies would accelerate the pace of space discovery while protecting astronaut lives.

Bretscher, H. S. & Fox, D. T. Proliferation of double-strand break-resistant polyploid cells requires Drosophila FANCD2. Dev Cell 37, 444–457 (2016).

Hashimoto, T. et al. Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein. Nat Comms 7, 12808 (2016).

Research Impact/Earth Benefits: In year 1 of our proposal we cloned 96 Tardigrade genes into Fruit Fly expression vectors. These vectors, and the transgenic flies that are deriving from them, represent a new resource for the study of Tardigrade gene products and their potential impact on the biology of extreme environmental stress resistance, including resistance to radiation.

Task Progress & Bibliography Information FY2019 
Task Progress: Original project aims/objectives:

(1) AIM1- A targeted Drosophila screen of candidate factors from Tardigrades (Ramazzottius varieornatus) that enhance radiation resistance. AIM2- An unbiased screen for genes that enhance radiation resistance in the Drosophila hindgut.

(2) Aim 1- In year 1 we cloned 96 Tardigrade genes into fly expression vectors and began generating transgenic flies from these cloned genes. We also established three independent screening assays to measure radiation resistance in response to both high (56Fe) and low (X-ray) linear energy transfer (LET) radiation. Aim 2- In year 1 we generated approx. 1,500 lethal mutant stocks in the genetic background required for our proposed ethyl methanesulfonate (EMS) screen, and began to optimize our conditions for our un-biased screen.

(3) In year 1 we made significant progress in our technology requirement needed for our screens to discover new radiation counter-measures.

(4) AIM1- As outlined in our proposal, we aim to identify single Tardigrade genes that, when expressed in another organism, confer increased radiation resistance. We proposed to use Drosophila to rapidly screen through single Tardigrade genes in a whole organism context. In year one, we made progress towards this goal on two major fronts. First, we initiated the creation of 96 transgenic fly lines, each expressing a single Tardigrade gene. Second, we established protocols for screening each transgenic line for increased radiation resistance. We have now cloned 96 distinct Tardigrade genes into fly expression vectors. For 36 of these genes, we have already performed all of the plasmid amplification, sequence verification, and embryo injection to produce stable transgenic lines. In the coming year we see no issues with meeting our proposal's stated goal of establishing approx. 100 transgenic lines, each expressing a Tardigrade-unique gene. Additionally, we established 3 independent assays for radiation resistance. Specifically, we now have repeatable assays to measure an irradiated animal's acute survival, lifespan, and fecundity. For low LET radiation, we have established 15 Gy of X-irradiation (at .16 MeV) at Duke's irradiator as our standard dose, and for high LET radiation we established 10 Gy of 56Fe (at 600 MeV/n) as our standard dose. The latter dose was determined in our first trip to NSRL in June. To summarize, at the end of year 1 we are in an excellent position to begin screening our Tardigrade gene-expressing flies in year 2, while continuing to generate and test additional lines. AIM2- As outlined in our proposal, we plan to conduct an unbiased screen for genes that are required for DNA damage resistance in the Drosophila hindgut. In year 1, we established 6161 fly lines from mutagenized parents. From these, we recovered 1467 independent lines carrying recessive lethal mutations on the X-chromosome. We will maintain these lines as heterozygotes, but the lines are in a background that permits site-specific recombination on the X-chromosome to yield homozygous mutant hindgut cells. In year two, we are now well-positioned to carry out the proposed screen of these now established lines for genes required for radiation resistance.

Bibliography Type: Description: (Last Updated: 01/15/2019)  Show Cumulative Bibliography Listing
 
Awards Fox D. "Invited speaker at the 64th Annual Meeting of Radiation Research Society, Chicago, IL, September 2018." Sep-2018
Awards Clay D. (Delisa Clay) "National Science Foundation graduate fellow, September 2018." Sep-2018
Project Title:  Mining Biology's Extremes for New Space Radiation Resistance Strategies Reduce
Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
TRISH--TRISH 
Start Date: 10/01/2017  
End Date: 09/30/2020  
Task Last Updated: 02/22/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Fox, Donald  Ph.D. / Duke University Medical Center 
Address:  Pharmacology & Cancer Center 
DUMC Box 3813, C318 LSRC 
Durham , NC 27710 
Email: don.fox@duke.edu 
Phone: 919-613-8756  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Duke University Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Kirsch, David  M.D., Ph.D. Duke University 
Project Information: Grant/Contract No. NNX16AO69A-T0108 
Responsible Center: TRISH 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2017 HERO NNJ16ZSA001N-TRIRT. Appendix C: Translational Research Institute for Space Health (TRISH) Research Topics 
Grant/Contract No.: NNX16AO69A-T0108 
Project Type: GROUND 
Flight Program:  
TechPort: No 
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:  
Human Research Program Elements: None
Human Research Program Risks: None
Human Research Program Gaps: None
Task Description: Using powerful genetic screening in Drosophila and follow-up work in mice, we will identify unique genes and gene expression that enhance space radiation tolerance in vivo. Our approach will identify new, organism-relevant strategies to provide space radiation resistance.

1-Specific Aims

Aim1- A targeted Drosophila screen of candidate factors from Tardigrades (Ramazzottius varieornatus) that enhance radiation resistance.

Aim2- An unbiased screen for genes that enhance radiation resistance in the Drosophila hindgut.

2-Relevance

The purpose of this proposal is to uncover new understanding of how a species withstands space-relevant radiation exposure, using validation and safety efficacy studies in model organisms. Drosophila is specifically mentioned, and we have expertise in study of Drosophila radiation resistance mechanisms (Bretscher and Fox 2016, Dev Cell). We will perform genetic manipulation in vivo in flies, targeting potential Tardigrade resilience mechanisms. Finally, we discuss follow-up work in rodents, which we are well-equipped to do, as Duke co-investigator Dr. Kirsch has prior NASA-funded experience in studying space radiation effects in mice at Brookhaven NASA Space Radiation Laboratory (NSRL).

3-Approach

Aim1- We will generate novel Drosophila strains expressing candidate Tardigrade genes, and assay their effects on resistance to both high charge and energy (HZE) particles (56Fe), and as a comparison, X-ray irradiation. Tardigrades have recently shown promise for finding factors that enhance radiation tolerance (Hashimoto et al., Nat. Comm. 2016). Genome data for this radiation-resistant organism is now available. From our collaborators Bob Goldstein, we will obtain animals for cDNA generation. We will generate up to 165 unique fly lines, each expressing a Tardigrade gene that, relative to Drosophila or humans, is is unique (low homology) and/or induced by radiation. Flies will then be subjected to HZE particles at NSRL or X-irradiation at Duke, and monitored for long-term survival, multi-generational fecundity, and will be sequenced at distinct generations to quantify radiation-induced mutations. Genes with promising enhanced radiation resistance will be pursued further in transgenic mice subjected to similar tests as in flies.

Aim2- Relative to candidate screens (Aim1), un-biased fly screens are more applicable to genome-wide study. The Fox laboratory recently identified a Drosophila cell type (hindgut papillar cells) that is highly resistant to X-irradiation, and used a simple in vivo candidate screen to find genes required for the heightened radiation resistance. Expanding on this successful strategy, we will screen 1/5 of the entire genome through EMS mutagenesis. Mutant strains will be assayed for DNA damage resistance in hindgut papillar cells. Interesting mutants will be sequenced to find causative genes. We will then generate transgenic flies expressing genes that mediate radiation resistance throughout the fly, and perform tests of HZE particle and X-irradiation resistance, including long-term organismal assays and follow-up mouse experiments as in Aim1.

4-Impact and 5-Rationale for mitigating space exploration risks

Space radiation poses a significant threat to astronaut health, and novel approaches are needed to limit space radiation damage. Drosophila and mice provide convenient, in vivo-relevant screening platforms, and effects on organism health, such as fecundity, can be scored. Understanding mechanisms that prevent space radiation damage in model organisms may uncover new space radiation resistance strategies to be targeted in humans. Such strategies would accelerate the pace of space discovery while protecting astronaut lives.

Bretscher, H. S. & Fox, D. T. Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2. Dev Cell 37, 444–457 (2016).

Hashimoto, T. et al. Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade -unique protein. Nat Comms 7, 12808 (2016).

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2018 
Task Progress: New project for FY2018.

Bibliography Type: Description: (Last Updated: 01/15/2019)  Show Cumulative Bibliography Listing
 
 None in FY 2018