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National Aeronautics and Space Administration

Radiation Research Society

Scholars in Training

October 15, 2016

Human Research Program

Space Radiation

Lisa C. Simonsen, Ph.D.

Element Scientist

NASA Space Radiation Program Element

Space Radiation Program Element

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Primary Hazards to Humans during Space Flight

Decreased gravity

• Bone Loss, Muscle Atrophy, Reduced Immune

Function, Fluid-Shifts

Isolation/confinement/altered light-dark cycles

• Sleep Issues, Psychological Stress

Hostile/closed environment

• Atmosphere, Microbes, Dust, Habitability

Distance from Earth

• Autonomy, Food Systems/Nutrition, Clinical

Medicine

Increased radiation

• Cancer, CNS, Cardiovascular and Degenerative

Changes, Acute Risks

Image Credit: NASA/Pat Rawlings, SAIC

Images courtesy of NASA


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• The Human Research Program (HRP) focuses on applied research

• Program goals

– Perform research necessary to understand and reduce spaceflight human

health and performance risks in support of exploration

– Enable development of human spaceflight medical and human performance

standards

– Develop and validate technologies that serve to characterize and reduce

medical risks associated with human spaceflight

Seat layout for contingency EVA Example of a study on the effects of center of gravity on performance

Clay Anderson centrifuges Nutrition

blood samples during Increment 15

An Applied Research Program

Images courtesy of NASA


Space Radiation Environment

Galactic Cosmic Rays (GCR) – chronic low-dose rate exposure

• Highly charged, energetic atomic nuclei (HZE particles) and protons

• Major types: H, He, C, O, Ne, Si, Ca & Fe; broad energy spectra

from ~10 to 10,000 MeV/n

• Not effectively shielded (fragment into lighter, penetrating species)

• Main challenge: uncertainty about biological effects limits

ability to evaluate risks and countermeasures

Solar Particle Events (SPE) – intermittent exposure

• Low to medium energy protons

• Shielding effective to prevent Acute Radiation Syndromes

• Main challenge: Optimized storm shelter mass, active

dosimetry, operational constraints/forecasting

Trapped Radiation (Van Allen Belts)

• Low to medium energy protons and electrons

• Effectively shielded

• Mainly relevant to ISS and contributes ~40% of dose equivalent

• Main challenge: develop accurate dynamic model

Image credit: NASA

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Image credit: NASA JPL

Image credit: NASA JPL

Image credit: NASA


Risks documented in HRP

Evidence Books

Space Radiation Health Risks

• Risk of Radiation Carcinogenesis

−Morbidity and mortality risks

• Risk of Acute (In-flight) & Late Central Nervous System

Effects from Radiation Exposure

−Changes in cognition, motor function, behavior and

mood, or neurological disorders

• Risk Of Cardiovascular Disease and Other

Degenerative Tissue Effects

–Degenerative changes in the cardiovascular system and

lens

–Diseases related to aging and immune system

dysfunction

• Risk of Acute Radiation Syndromes due to Solar

Particle Events

–Prodromal effects (nausea, vomiting, anorexia, and

fatigue)

–Skin injury

–Depletion of the blood-forming organs and immune

dysfunction6


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Current and Future Human Space Missions

International Space Station

‒ 2013-2024: 6-person crews for 6 months; 2-person crews for 12

months

‒ Dose limits reached after 1-3 missions

Deep Space Journey/Hab: (Lagrange Points, Near Earth Objects, 1 yr.)

‒ Outside Earth’s magnetosphere in free space; no planetary protection;

GCR risks major concern

‒ Limited number of crew will certify for flight – duration dependent

Planetary: Mars

‒ 2030 and beyond: 6-person crews, up to 3 yrs.

‒ Long deep space transit times; mixed field environment on Mars

‒ 3 to 4 times over current Permissible Exposure Limits

Radiation doses are mission specific:

• Destination and duration • Vehicle and habitat design • Solar conditions

Images Credit: NASA

National Aeronautics and Space Administration

Image credit: BNL Image credit: BNL

Images credit: OLTARIS.nasa.gov

(top) and NASA (lower)

Image credit:

NASA

Image credit: NASA

Image credit: NASA

Background Image credit: NASA

Image credit: NASA

Image credit:

NASA

Image credit: NASAImage credit: BNL

Image credit:

SwRI

JOHN FRASSANITO & ASSOC. © 2002

Image credit: NASA Image credit: NASA

Dr. Karl Johnson © 2004

Image credit: NASA/NIAC

Image: Public Domain

Datta et al. (PLoS One 2012)

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The Biological Perspective:

Research Challenges

H2AX foci (green) mark DNA double

strand breaks in nuclei of human

epithelial cells after radiation exposure

• Understanding Radiation quality effects on

biological damage

− Qualitative and quantitative differences between

space radiation compared with x-rays or gamma-

rays

• Quantifying low dose and dose rate dependencies

‾ Biology of repair, cell, and tissue regulation

• Translating experimental data to humans

− Lack of human data exist to estimate risk from high

LET GCR exposures

− Animal and cellular models with simulated space

radiation must be used

• Understanding Individual radiation sensitivity

‾ Genetic, dietary and healthy worker effects

• Quantifying synergistic modifiers of risk from other

spaceflight factors

Densely ionizing radiation along

particle track cause unique damage

to biomolecules, cells, and tissue

(Cucinotta & Saganti, Patel & Huff, NASA)

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Foundation of

Space Radiation Research Plan

• The Space Radiation Integrated Research Plan

(http://humanresearchroadmap.nasa.gov/)

• External review by NCRP, NAS, and annual

NASA Standing Review Panels

• Broad program of solicited, peer-reviewed

research at over 40 US Universities

• Ground based studies with space radiation

simulated at the NASA Space Radiation

Laboratory

• Collaborations with other NASA Programs and

Agencies support an integrated protection

strategy across physical and biological solutions

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Images Courtesy of Brookhaven National Laboratory (BNL)

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• Simulates space radiation - high

energy ion beams (H+, He, Fe, Si,

C, O, Cl, Ti, etc.)

• Biology labs and animal care

• Facility upgrades for GCR simulator

complete in late 2016

• 3 experimental campaigns per year

NSRL Beam LineImages courtesy of BNL

NASA Space Radiation Laboratory (NSRL) at Brookhaven National Lab

NSRL

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TANDEM


NSRL Upgrades: Galactic Cosmic Ray Simulator

1.5 GeV/n Beam• Added magnets

and power source

Fast Multi-Ion Selector• LIS and EBIS Setup• RF modifications• Controls system

Simulation of the GCR primary

and secondary environment

with a mixed field, high-energy

capability:

‾Magnet upgrades for delivery of

beams at 1.5 GeV/n

‾Rapidly switchable ion source

‾Automated controls

‾GCR species will be simulated

with high precision in major LET

bins ranging between 0.25 - 1,000

keV/µm

–Completion in late 2016

–Strategies for chronic exposures

12Images courtesy of BNL


Radiation Carcinogenesis Research Focus

• Continued focus on radiation quality and dose-rate

effects on cancer processes:

- Mechanistic analysis of cancer risk including enhanced

aggression observed in HZE tumors

- Impact of non-targeted effects at low doses

- Understanding the biological basis for sex differences and

individual sensitivity

• Research incorporating new integrative “omics”

techniques and systems biology approaches

‾ Identification of biomarkers for early disease detection and

health monitoring

‾ Discovery and validation of biological countermeasures

• Development of an integrated risk model with

acceptable uncertainty in support of meeting PELs for

exploration Gene analysis can support the determination of

survival outcome of patients with lung cancer

(UTSW NSCOR, PI: J. Minna)

Greater Incidence (%) of HCC with metastases

to the lung with High LET radiation.

(UTMB NSCOR, PI: R. Ullrich)

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• Current research is focused on understanding and

quantifying the risk of cardiovascular disease at

space relevant exposures:

- Identify disease spectrum and latency for low

dose heavy ions

- Establishing dose thresholds for heavy ions

- Understand qualitative differences between

GCR and gamma-rays to quantify RBEs

- Dose-rate effects

• Identify and validate surrogate biomarkers for

radiation induced disease endpoints

• Future studies will address impact of individual

sensitivity and other spaceflight stressors

Vasculature damage in 3D

endothelial cell cultures

following Fe irradiation (PI-

Grabham)

Controls

Iron Irradiated

Cardiovascular Disease from Space Radiation Research Focus

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In-flight/Late CNS Effects from Space Radiation Research Focus

• Focus on CNS risk definition and characterization

• Understanding whether there are significant risks at

space relevant exposures

– Description of the spectrum and severity of

possible in-flight cognitive, behavioral, and

functional changes as well as possible late

neurodegenerative conditions

– Mechanistic basis for observed CNS decrements

– Radiation quality and dose-rate dependencies

– Establish possibility of dose thresholds

• Identification of biomarkers related to early cognitive

and behavioral decrements and relationship to late

degenerative changes

• Research addressing sleep and exercise as

countermeasures as well understanding synergistic

effects of spaceflight

Eating, sleeping and working in space

Images courtesy of NASA 15


Risk of Acute Radiation Syndromes from a SPEResearch Focus

• Research addresses magnitude of acute health

effects from whole-body exposures to protons

from an SPE

– Characterized by high degree of variability in

dose distribution and dynamic changes in

dose-rates and energy spectra over the

course of the event

• Current NSBRI-CSRR research:

– Understand impact of high skin dose on immune

system and blood forming organs

– Assess validity of current PELs

– Microgravity effects

– Countermeasures

• NASA ARRBOD model predicts severity of acute

radiation syndrome

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• Time in solar cycle and ability

to minimize exposure to SPE’s

• Accurate risk quantification /

uncertainty reduction

• Crew Selection− Age, gender, lifestyle factors, etc.

− Individual Sensitivity (genetic

factors)

• Biomarkers predictive of

radiation induced diseases − Future individualized risk

assessment

− Early detection and surveillance

• Biological Countermeasures

– Radioprotectors / Mitigators

− Nutritional

• Radiation Shielding− Amounts and material types

− Design optimization Shield Design and Optimization

Variation of Solar Activity

BCM: Pharmaceuticals

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amifostine

Authorized usage under Ganfyd-license

α-lipoic acid

Image credit: Ben Mills

Image courtesy of OLTARIS.nasa.gov

Exercise and Conditioning

Image courtesy of NASA

Protection and Mitigation Approaches


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Multiple effects to consider

Current research provides evidence base and

mechanistic understanding

Developing strategies for implementation of testing

within NASA & FDA guidelines

Leverage shared interest in countermeasures with

external agencies

Developing advanced analytics tools (ex. IBM

Watson) to link large body of biomedical data to

NASA problem

NASA Unique Problem: Understanding efficacy in low dose, mixed field

radiation environment — validation requires GCR Simulator

Approaches to Medical Countermeasures

Supporting Deep Space Exploration


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Requirements driven by mission operations:

– Conservative prophylactic use; no designer drugs, must demonstrate proven long term

use, minimal side effects

– FDA approved, FDA Off-label, FDA IND Status drugs

– Dietary supplements

Biological countermeasure criteria:

– Mechanism of action well known; independent of sex

– Chronic administration (potentially up to 3 years)

– Easily self administered (e.g. Oral, inhaled)

– No contraindications with other drugs

– Long shelf-life

Categories of Potential Agents:

‒ Cross-risk agents targeting common pathways (ex. anti-inflammatory agents)

‒ Radioprotective/mitigating agents targeting early damage and acute effects; potential for

cross-over to late effects

GCR Biomedical Countermeasures

Evaluate countermeasures developed for ARS or protection

during radiotherapy under SBIR (to be released Fall 2016)

using mixed field (high LET + low LET)


https://humanresearchroadmap.nasa.gov/

Integrated Research PlanRisks – Research Gaps – Tasks – Deliverables

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Future Funding Opportunities

NRA Flagship Topics: Primary mechanism for soliciting grants

• HERO solicitation: Appendices with Flagship Topics released two to three times a

year — Space Radiation targets early spring

• Typically $300K to $450K per year for 3 to 4 year

Omnibus Grants: Released as Appendix ~ once a year

• Short-term investigations addressing any risk/gap in the Integrated Research Plan

• No more than 1 year and cost no more than $100K total per award

Basic Investigations for New Investigators: Released as Appendix ~ once a year

• Investigations can address any aspect of human adaptation to space flight

• Open to new investigators only (no NASA or NSBRI funding as PI in the last 10 yrs)

• Project must adhere to Omnibus guidelines (budget and duration), but can be

renewed for one year based on progress

NASA Research Opportunities

https://nspires.nasaprs.com/external/

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• NASA and BNL have established an

agreement to allow interested

investigators to perform “Piggyback”

experiments for the purpose of

obtaining preliminary data to support

future proposal development.

Piggy Back Experiments at BNL

• Modest studies are permitted which must be

conducted within the resources of a currently

funded Space Radiation principal investigator’s

peer reviewed and approved project.

• Piggyback experiments are allowed once every

three years.

• Interested parties should contact BNL (email:

[email protected]) to learn about the

specific application requirements.

Images credit: Brookhaven National Laboratory (BNL)

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Space Radiation Summer School

Website opens –

End of October/Early

November

Applications typically due in

early February

13th annual NASA Space Radiation Summer School (2016) 23


Example — NRA Topic Areas

Research Emphases:

• Cognitive and Behavioral Central Nervous System Risks from Space Radiation

• Cardiovascular Disease from Space Radiation

• Cancer Risks from Space Radiation

• Special Topic: GCR Simulator Validation Experiments

• Special Topic: Biological Countermeasures for Space Radiation Carcinogenesis

• Special Topic: System Radiobiology: Developing Multiscale Models for Risk

Prediction of Radiation Induced Disease

• HERO Flagship Topic: Space Radiobiology Tissue Sharing: Research Proposing

the Use of Archived Tissue Samples or Samples from On-going Experiments

• NASA Specialized Centers of Research (NSCORs) for Ground-Based Studies

Assessing Cancer Risks from Space Radiation and the Impact of Individual

Susceptibility

Clearly identified Specific Research Gaps for each Topic Area24


Additional Guidance

• Multiple animal models that can extend findings to larger species should be considered.

• Creative proposals addressing multiple risks in a cost effective manner are also encouraged.

• Studies proposing the sharing of experimental animals and tissues across risk areas and from

currently funded investigations are highly encouraged.

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• For proposals utilizing animal models, proposers are

encouraged to use animals reflective of the astronaut

population:

– Average age is 35-55 years old with first space

mission at the age 47 for ISS crews

– Current corps is approximately 30% female

– Most astronauts are lifetime never-smokers.

– Experimental studies should reflect healthy lifestyle

factors (never-smokers, normal weight, diet) Image courtesy of NASA


• Studies must also include an experimental component incorporating a mixed field

radiation environment at dose/dose-rates that can be experimentally justified for the

model system selected.

• Research should emphasize the major tissues (Gap-1: lung, colon, liver, stomach,

breast, and leukemia) with emphasis on stomach and breast as well as the bladder and

ovaries (Gap-2).

Proposals addressing liver and non-melanoma skin cancers are not requested

A high priority research area is understanding the biological basis for predicted sex

differences and individual sensitivity on lung cancer risks.

• Proposed studies must link radiation exposure to the development of clearly justified

disease endpoints representing clinically significant cardiovascular disease outcomes

• Doses corresponding to HZE particles at low fluence (less than one ion per cell), proton

doses up to 1.0 Gy, and HZE particles at low doses no higher than 0.5 Gy.

• Experimental protocols should reflect careful consideration of irradiation requirements,

including justified estimates of dose, dose rates, and ion beams for selected samples as

well as a description of the range of possible sample sizes and their associated power.

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Additional Guidance


Example — NRA Solicitation Submission and Review Process

• NRA Issued: March 4

• Step-1 Proposals Due: April 3

• Relevancy Review:

− Does this study address a research emphasis stated in

solicitation?

− Program Invites for Step 2’s (April 22)

• Step-2 Proposals Due: June 22

• Merit Review: Late July

− NASA Research and Education Support Services

– Peer Review Panels organized by subject area

• SR Review (Relevancy and Balance): August/Sept.

• Recommendations for Selection: Late Sept

• Final Selection Notification: mid October

• Awards through NASA Shared Services Center (NSSC):

Dec. through Feb timeframe

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NASA Research Opportunities

https://nspires.nasaprs.com/external/


Merit Review: Science and Technical

1. Significance: Does this study address an important problem?

How will scientific knowledge or technology be advanced?

2. Approach: Does the applicant acknowledge potential

problem areas and consider alternative tactics?

3. Innovation: Does the project employ appropriate novel

concepts, approaches, or methods? Are the aims original?

4. Statistical Plan (Strengths and Weaknesses): Does the

study provide adequate justification for sample size? Are

assumed effect magnitudes reasonable? Are assumed

variability estimates reasonable?

5. Investigators (Strengths and Weaknesses): Is the work

proposed appropriate to the experience level of the principal

investigator and any co-investigators? Is the evidence of the

investigators' productivity satisfactory?

6. Environment (Strengths and Weaknesses): Does the

scientific environment in which the work will be performed

contribute to the probability of success?

7. Overall Evaluation (balance of strengths and weaknesses)

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Proposed sampling

procedure, experimental

design, and data analysis

methodology will be

evaluated by statistician on

review panel

Peer reviewed publications

matter!

An investigation should

significantly contribute to the

risk-reduction focus of HRP

Final Merit score based on

consensus — No. of major

vs minor


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Merit Peer Review – Proposal Scoring

Scientific/technical merit of the proposal places it among the top 10%. A

proposal that has several strengths, no major weaknesses, and very few or no

minor weaknesses.

EXCELLENT

90-100

Scientific/technical merit of the proposal places it among the top 20% (but NOT

the top 10%). A proposal that has one or more strengths, no major weaknesses,

and minor weaknesses that are substantially outweighed by the strengths.

VERY GOOD

80-89


the top 20%). A proposal that has no major weaknesses, several minor

weaknesses, but sufficient strengths to balance and compensate for the minor

weaknesses.

GOOD

70-79


the top 30%). A proposal that has one or more major weaknesses, and in which

the major and minor weaknesses clearly compromise any strengths.

FAIR

50-69

Scientific/technical merit of the proposal places it in the lower 50%. A proposal

that has several major weaknesses that would require major revisions to

correct.

POOR

<50

Not Recommended for Further Consideration. A proposal that is judged by

unanimous consent of the panel to be unlikely to benefit from revision or a

revised proposal in which little or no effort has been made to address previous

review comments.

NRFC


Special Topic 01 (ST-01): GCR Simulator

Validation Experiments

IRP Risk: Risk of Radiation Carcinogenesis & Risk of In flight and Late CNS Effects

IRP Gaps: Cancer 3, Cancer 4, CNS 5, CNS 6

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Mixed field proof of concept studies, comparing predicted model outcomes

with experimental results, are sought to answer the following questions.

• How many different particles are sufficient to adequately simulate the biological

and health consequences of GCR across risk areas? What is the time scale

(dose rate and duration) and order of delivery of particle types?

• What mixed radiation field, including protons, helium and heavier nuclei,

provides the most stringent tests of model predictions? Is there an intermediate

capability that may provide a similar statistical power for determining the

validation of radiation models?

Additional Guidance

• Studies should consider the GCR simulation capability currently being designed

at NSRL as described above, as well as, other possible approaches

• Proposed studies making use of existing data sets or that are directly relatable to

past data sets are highly desirable.

• Studies that investigate mixed field dose response curves are of interest.


Blakely, Simulation of GCR-Induced Harderian Gland and Lung Tumorigenesis (LBNL)

Uses existing data on Harderian gland tumorigenesis from individual HZE ion beams to predict

outcome of mixed ion chronic GCR exposures, measure Harderian gland and lung dose-dependent

tumor data.

Kronenberg, GCR Simulator Validation Studies with Human and Mouse Models (LBNL)

Investigates cancer relevant endpoints (mutagenesis and cytotoxicity) measured in complimentary

human and mouse cell lines and animal model to facilitate design of the GCR simulator..

Complimentary Studies

• Both Studies leverage on PI’s substantial historical (>20 yrs.) data-sets using single ion beams

• Complimentary cell lines and mouse models within and across studies

• Address important questions on how tumor prevalence and carcinogenic endpoints may change in

response to a mixed field GCR including issues related to additivity of carcinogenic effects

• Will address the feasibility of simulating the complex radiation field with only a few ion species

• Blakely will address issue of non-targeted effects at low particle fluence using tumor endpoint and will

generate mathematical model for mixed beams supporting risk estimation for mission relevant

exposures

• Kronenberg will address protracted exposures over 20 days and fill in data gaps for He ions

representative of 20% of the dose

• Provides the biological validation required to extend cancer risk assessment computational models

over a broader range of experimental conditions helping to reduce uncertainties in radiation quality

effects and dose-rate dependence31

Selection Summary:

ST-01 GCR Simulator Validation Study


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NASA Selection – After Merit Review

Consider programmatic balance and

cost of all proposals in the fundable

range – 70 or greater

– Alignment with the Integrated Research

Plan

– Evaluate how the proposed work may

help achieve an appropriate balance of

scientific and technical tasks required to

understand and mitigate our Risks

– Evaluate the reasonableness of

proposed costs compared with available

funds

– Relevancy of research to support our

delivery of mitigation strategies to

operations in time to meet Exploration

mission needs

http://humanresearchroadmap.nasa.gov/

https://taskbook.nasaprs.com


Pre – Mission Post – MissionIn – Mission

• Mission Location & Duration

• Solar Conditions - Min vs. Max

• Optimized GCR Shielding with

Storm Shelter

• Operational Planning;

Monitoring/Dosimetry

• Biomedical Countermeasures*

/Radioprotectants

(Pharmaceutical, Nutritional,

Exercise)

• Space Rad Environmental

Models and Mission Design

(ALARA)

• Accurate Models of Risk

Projection – Increase safe days

in space

• Crew Selection – age, sex,

healthy worker effects

• Understanding Individual

Sensitivity*

(Genetics, Biomarkers)*long-term

development

Reduction in Total Risk Posture

• Occupational Health Care for

Astronauts*

• Advances in Treatments –

Precision Medicine*

• Biomarkers: personal risk

assessment, health

monitoring for early disease

detection

• Biomedical

Countermeasures*/Mitigators

Enables longer mission durations

Allows for larger portion of crew

office to qualify for flight

Early detection and

prevention of radiation

induced diseases to increase

quality of life & outcome

SR Research Products Mitigate Risk across all Phases of Mars Mission

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Know the Programmatic needs –address them directly in your application

• HRP is a well-documented Program

• Applied Research Program (TRL 4-6) — not basic science

• Investigations should significantly contribute to the risk-reduction

focus of HRP

• Constraints on schedule, crew access, and need for risk mitigation

are different from those in NIH and NSF solicitations

• Looking at past solicitations may provide additional insights

• Very helpful to talk with other funded PI’s familiar with Program

• Partnering with an established researcher may be beneficial

When you listen to talks during this meeting — pay attention to who funded

the research…

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Do read the entire Solicitation

• Pay attention to what the solicitation is specifically requesting

• Background sections describe our problem, strategies, and research

needs

• Your proposed research must be relevant to our objectives and

deliverables

• Look at links provided

• NASA Taskbook describes work currently being performed as well as

past studies

• My contact information is included in solicitation – don’t be afraid to

contact me if you have questions

• Don’t try to force your research into a topic area if it doesn’t fit what we

are requesting

“If the sponsor wants bananas don’t try to sell them apples, even if you

have a Nobel Prize in apples.”

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• Make sure you know requirements (page limits, deadlines, etc.)

• Non-compliant proposals are not reviewed

• Know the evaluation Criteria for Scientific Merit before you start writing

• NASA announcements have unique requirements (e.g. gap

identification, VASR)

For Step-2 proposals: Proposals must identify Integrated Research Plan risks and gaps

addressed by the research (Section I.D).

For Step-2 proposals: If using vertebrate animals, your proposal must meet

requirements of the Vertebrate Animal Scientific Review section of this solicitation

(Sections IV.B.3.f and Appendix B).

For Step-2 proposals: A thorough statistical section must be included which includes a

power analysis for the estimate of sample size and the comparison of males and

females unless compelling evidence is provided that shows that no gender differences

are expected.

Do read the entire Solicitation

36


Pay attention to bold sentences

• Highlights requirements especially those that will be considered as not

responsive

– In order to be considered responsive to this special topic area, all Step 1 and Step 2

proposals must clearly describe how the proposed biological countermeasure

addresses the requirements listed above. Proposals that do not provide convincing

evidence will not be selected for Step-2 submit.

• We identify what we are interested in as well as what we are not

interested in—provides insight into programmatic relevancy and priorities!

– Research should emphasize the major tissues (Gap-1: lung, colon, liver, stomach,

breast, and leukemia) with emphasis on stomach and breast as well as the bladder and

ovaries (Gap-2).

• Proposals addressing liver and non-melanoma skin cancers are not requested

• A high priority research area is understanding the biological basis for predicted sex

differences and individual sensitivity on lung cancer risks

37


Getting Started – Writing your grant application

• First Page and Introduction are critical:

– Start with the big picture at the educated layman’s level and then

add detail

– Clearly state the idea. Why should anyone care about your

approach? What’s novel about it?

– Identify how proposed research is responsive to solicitation and

relevant to NASA

– Get reviewers excited about your ideas!

• Background is extremely Important:

– Must show your knowledge of current relevant research

– What’s already been done – NASA Taskbook helps with this!

– State how your proposed research will the advance scientific

knowledge

• Don’t recite the solicitation contents back to us

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Experimental Design/Approach:

• Clearly identify your experimental models – cells, tissues, animals? If multiple

models, are they complimentary? How will you evaluate/validate results

across model systems?

• Discuss the time dependence, following radiation exposure, of the effects you

will measure on the likely evolution of the model systems studied?

• Examples: chemical recombination; DNA repair; cell signaling; initiation vs.

promotion vs. progression; latency of disease appearance; development of

metastases

• What will you measure and when?

– Examples: number of colonies on Petri dishes 24 hours after irradiation;

concentration of molecular yields 2 hours after the end of the exposure;

number of tumors on mice after 6, 12, and 24 months.

• What is the Sensitivity of your measurements to dose or fluence required to

provide a statistically significant measurement.

• How will you interpret results?

• What are your controls? How are they handled?

• Is your statistical power sufficient?

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Making your Case I

• Address potential pitfalls up front (show reviewers you have thought

this through). Explain options if the initial approach is unproductive.

• Do you have preliminary data that demonstrates that you are able to

do the technical things you propose?

– Are they at relevant exposure levels? Are they at endpoints

relevant to NASA?

– Are there other relevant data sets in literature that can support

your proposal?

– Piggy back experiments are possible at NSRL

– Pilot studies can be recommended at review

40


Making your Case II

• If you reference a figure, “pre-print,” or “publication” –make sure it

supports the case you are making – with statistical significance!

• Reviewers read your references as well as perform their own

literature searches

• Define your terminology well – reviewers may not be familiar with

your specific techniques. No slang terms.

• Make sure a peer reads your proposal for clarity well before

submission.

– Most importantly, listen to their feedback; if they don’t get it – it’s

highly likely that some reviewers won’t either!

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Don’t distract the reviewers from your science!

• Sloppy language, spelling, punctuation suggests general

sloppy thinking and carelessness.

• Double check for misplaced or incorrect references.

• Don’t use overly complex sentences with multiple

clauses, and avoid awkward punctuation.

• If you “re-purpose” a grant, remove references to the

other Program’s Solicitation

• Easily understood (clear, high resolution) figures and

legends are a must!

42


Panel comments that result in low scores –

• Lack of preliminary data

• Data does not substantiate their claims

• Models not relevant to endpoints

• So poorly written, message is unclear

• Doses too high—not space relevant exposures

• Not enough statistical power

43


A well thought-out plan – Research, Budget and Schedule align!

• Make sure your plan is realistic within time and budget guidance

• An early sketch of a schedule will help scope your project

– Provides an overall feel of what can realistically be accomplished within the grant

period

– Identify a few well-defined steps in achieving each specific aim

• How long will they take?

• What experiments will depend on previous work?

• Who will do what?

• When is travel needed?

• Does you plan align with NASA Space Radiation Laboratory experimental run schedules?

– Will help you allocate resources

• Does your budget match your plan?

– If you are proposing 3 runs at NSRL – your budget should show costs for three trips to

New York….

– If you have 100 animals, there should be husbandry costs for 100 animals…

• Everyone on Grant should be critical to the success of the grant with clearly defined roles

and responsibilities

• Save quotes utilized for your Budget Justification – NSSC will require these44


Don’t wait until the last minute

• Log into NSPIRES early to establish accounts – both

PI’s and Co-I’s

• Give a heads up – make sure your Institution knows you

are submitting a grant

• Avoid system upload problems, help desk goes home,

Authorizing Official not available, etc., …

• Late proposals are not accepted

45


Don’t get discouraged!

• Many experienced PI’s are not selected for award

• Smaller opportunities (Basic New Investigations, etc.)

provide excellent mechanism to gain experience

• Merit scores are by consensus

• Strong dissenting opinions are documented

• Pay attention to major vs minor strengths and weaknesses

• You now have the benefit of expert opinion and

suggestions

• Use opportunity to address reviewers comment in re-submit

to make a stronger proposal46


Questions?

A cluster of massive stars NGC 3603 seen with the Hubble Space Telescope.

Credits: NASA/U. Virginia/INAF, Bologna, Italy/USRA/Ames/STScI/AURA 47

national aeronautics and space administration human ...€¦ · space radiation program element 7...

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