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High-Throughput Platform for Identification of Senescence AlteringTherapeutics Post Space Radiation Exposure

Description:

ScopeTitle:

High-Throughput Platform forIdentification of Senescence-Altering Therapeutics Post Space RadiationExposure

ScopeDescription:

Thisscope solicits proposals to identify a high-throughput CM screeningplatform that quantifies the effectiveness of CMs in reducingthe consequences of and/or number of senescent cells in ionizedirradiated cells, tissues, or surrogate models relevant to spaceexploration. A successful application would identify a screeningplatform capable of high-throughput capacity (96-well plate orsuperior/alternative throughput) usingimaging-based cytometry or comparable techniques. Alsodesired is a proof of principle demonstration that CMs targetingsenescent pathways (senolytic drugs, gene editing, gene therapy,biomolecule-based alternative methodologies, etc.) are effective againstionizing radiation (IR).

In Phase I of the project, the efficacyand sensitivity of the platform in measuring radiation-inducedsenescence as well as a known senescence-modifying therapy inconjunction with IR should be demonstrated. Requireddeliverables for the Phase I will be: 1) data generated from theplatform demonstrating sensitivity to changes in IR-induced cellularsenescence in a high-throughput capacity, and 2) data demonstrating thata known senescence-modulating intervention can be screened. This testingcan be done with cell models at the location of choice using y rays, xrays, and/or proton irradiation and do not require irradiationusing high-energy and charged ions. After contract award, due to thenature of this research, the contractor should immediately coordinatewith their technical monitor for any special considerations for testingand guidance on relevant radiation doses. In Phase II of theproject, we would expect testing to be expanded to include combinationsof different particles and energies that better simulate the spaceradiation environment.

Expected TRL or TRL Range at completion of theProject: 3 to 4

Primary TechnologyTaxonomy:

  • Level 1 06 HumanHealth, Life Support, and HabitationSystems
  • Level 2 06.5Radiation

DesiredDeliverables of Phase I and PhaseII:

  • Research
  • Analysis
  • Prototype

DesiredDeliverables Description:

Required deliverables for Phase I will be: 1) data generated fromthe platform to demonstrate sensitivity to changes in IR-inducedcellular senescence in a high-throughput capacity, and 2) datademonstrating that a known senescence-modulating intervention can bescreened. Phase I will demonstrate a platform for assessing, in ahigh-throughput capacity, the ability to screen therapeutics for thepotential use of reducing the long-term health impacts of IR-inducedsenescence. Phase II will identify CM approaches using the platformestablished in Phase I to reduce the consequences of cellular senescencearising from space radiation exposures. A test plan for in vivoevaluation that describes the expected effect from the therapeuticshould be included. Access and funding to support testing in spaceradiation simulated facilities will be provided for Phase II in additionto the standard award.

State of the Art and CriticalGaps:

Exposure of crewmembers to space radiation during lunar andMars missions can potentially impact the success of the missions andcause long-term decrements. Space radiation risks include cancer, lateand early central nervous system (CNS) effects, cardiovasculardiseases (CVD), and accelerated aging. This subtopic addresses thedevelopment of a screening technique to identity CMs that can reducesenescent cell population or SASPs and thus the potential tomitigate one or several of the identified space radiation risks.Countermeasures for adverse health effects from radiation exposure areof interest to the Department of Defense (DoD), the Department ofHomeland Security (DHS), and the radiation therapy community aswell.

Relevance / ScienceTraceability:

This subtopic seeks technology development thatbenefits the Space Radiation Element of the NASA Human Research Program(HRP). Senescent cell populations are rapidly becoming a subject ofconcern regarding not only degenerative disease but alsodiseases as diverse as cancer and diabetes. Potential benefits andinterventional, therapeutic approaches can help to identify newmodalities to improve long-term health outcomes arising from spaceradiation exposure.

References:
The followingreferences discuss the different health effects NASA has identified inregard to space radiation exposure:

  • Evidence report on central nervous systems effects: https://humanresearchroadmap.nasa.gov/evidence/reports/CNS.pdf
  • Evidence report on degenerative tissue effects: https://humanresearchroadmap.nasa.gov/evidence/reports/Degen.pdf
  • Evidence report on carcinogenesis: https://humanresearchroadmap.nasa.gov/evidence/reports/Cancer.pdf

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