# Gene expressions in human exploration beyond low earth orbits

Gene expressions in human exploration beyond low earth orbits is a proposal in response to NASA’s Human Research Program (HRP) NRA NNJ15ZSA001N-OMNIBUS "NASA Human Research Program Omnibus Opportunity", 2015. The same announcement has reoccurred: "All due dates and notification dates for NASA Research Announcement (NRA) 80JSC017N0001-FLAGSHIP1 and 80JSC017N0001-OMNIBUS ("NASA Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions" and "NASA Human Research Program Omnibus Opportunity", respectively) have been extended one additional week. [Step-1 Proposals Due: September 19, 2017, 5 PM Eastern Time]"
NASA is soliciting investigations lasting no more than one year that provide innovative approaches to any of the defined risks contained in the Integrated Research Plan (http://humanresearchroadmap.nasa.gov) of the Human Research Program. NASA is also soliciting novel research ideas that might not be directly aligned with HRP’s identified risks from new investigators who have not received NASA or NSBRI funding in the last ten years.
All categories of United States (U.S.) institutions are eligible to submit proposals in response to the NRA. Principal Investigators may collaborate with universities, Federal Government laboratories, the private sector, and state and local government laboratories. In all such arrangements, the applying entity is expected to be responsible for administering the project according to the management approach presented in the proposal. NASA’s policy is to conduct research with non-U.S. organizations on a cooperative, no exchange-of-funds basis.

## Gene project

The gene project is currently focused on gene transcriptions.

## Gene expressions

Risks summarized in the above announcement include physiological and performance effects from hazards such as radiation, altered gravity, and hostile environments.
Normal (Earth-based) gene expression may produce physiological and performance effects from the hazards mentioned.
Under, or over expression, of genes perhaps induced by onboard treatments may alter gene expression sufficiently to reduce adverse effects.
Altered treatments for preparation to return to normal (Earth-based) environments may reduce hazards before return to Earth.

## Human Research Roadmap

Human Research Roadmap The objective of this proposal is to explore each avenue of the roadmap to determine gene suites that may be contributing to or causing these effects or increasing risks of these effects sufficiently to adversely affect astronaut functioning.
1. BEHAVIORAL HEALTH AND PERFORMANCE
   * Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
   * Risk of Performance and Behavioral Health Decrements Due to Inadequate Cooperation, Coordination, Communication, and Psychosocial Adaptation within a Team
   * Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload
2. EXPLORATION MEDICAL CAPABILITY
   * Risk of Bone Fracture due to Spaceflight-induced Changes to Bone
   * Risk of Ineffective or Toxic Medications Due to Long Term Storage
   * Risk of Renal Stone Formation
   * Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities
3. HUMAN HEALTH COUNTERMEASURES
   * Concern of Clinically Relevant Unpredicted Effects of Medication
   * Concern of Intervertebral Disc Damage upon and immediately after re-exposure to Gravity
   * Risk of Adverse Health Event Due to Altered Immune Response
   * Risk of Cardiac Rhythm Problems
   * Risk of Decompression Sickness
   * Risk Of Early Onset Osteoporosis Due To Spaceflight
   * Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight
   * Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance
   * Risk of Inadequate Nutrition
   * Risk of Injury and Compromised Performance Due to EVA Operations
   * Risk of Orthostatic Intolerance During Re-Exposure to Gravity
   * Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity
   * Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations
4. SPACE HUMAN FACTORS AND HABITABILITY
   * Risk of Adverse Health & Performance Effects of Celestial Dust Exposure
   * Risk of Adverse Health Effects Due to Host-Microorganism Interactions
   * Risk of an Incompatible Vehicle/Habitat Design
   * Risk of Inadequate Design of Human and Automation/Robotic Integration
   * Risk of Inadequate Human-Computer Interaction
   * Risk of Inadequate Task Design
   * Risk of Injury from Dynamic Loads
   * Risk of Performance Decrement and Crew Illness Due to an Inadequate Food System
   * Risk of Performance Errors Due to Training Deficiencies
5. SPACE RADIATION
   * Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
   * Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs)
   * Risk Of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure
   * Risk of Radiation Carcinogenesis

## Funding proposals

Title: Gene expressions in human exploration beyond low earth orbits.
Number: 15-15Omni1-0008.
Solicitation: NNJ15ZSA001N-OMNIBUS
Step 1 submission: 08/31/2015.
Result:
* "The review of the Step-1 proposals received in response to the NASA Research Announcement (NRA) NNJ15ZSA001N-OMNIBUS “Human Exploration Research Opportunities” has been completed. Your proposal has been found responsive to the research emphases outlined in the NRA, and you are invited to submit a full Step-2 Omnibus proposal."
* "You are strongly encouraged to check the solicitation page in NSPIRES periodically for notices and FAQ updates prior to the November 23, 2015 proposal due date as new and updated information will be made available throughout the solicitation open period (tinyurl.com/2015-OMNIBUS)."
* "Your Step-2 proposal must be compliant with respect to Section D.3 of the NRA. Step-2 proposals will undergo scientific peer review as well as programmatic balance and cost review as outlined in Sections E.2 and E.3 of the NRA."
Step 2 submission (using 2015+HERO+Overview+7-31-15.pdf:
* Section D.3 of the NRA: "If a commercial organization wants to receive a grant, cost sharing is required unless the commercial organization can demonstrate that they are unlikely to receive substantial compensating benefits for performance of the work. If no substantial compensating benefits are likely to be received, then cost sharing is not required, but can be accepted. Acceptable forms of cost sharing are discussed in NFS 1816.303-70: http://prod.nais.nasa.gov/cgi- bin/common/wg/mfs.cgi/data/glimpse/archives/63?link=http://prod.nais.nasa.gov:80/far/far0553- nfs0463/1816.htm&file=/data/web/html/far/far0553-nfs0463/1816.htm&line=528#mfs."
* Section E.2 of the NRA: "The three types of objectives listed in section B.2 of this document give rise to three types of research products. If applicable for the specific research topic, proposers will identify, through answers to questions prompted by NSPIRES, which of the three types of research products best characterizes the proposed research:"
       1. For the quantification of a crew health and performance risk objective, the research product should define the likelihood or the consequence of a risk more completely. Such proposals must specify how much the uncertainty in the likelihood or the consequence of the risk is anticipated to be reduced by the proposed research.
       2. For the countermeasure development objective, the research product should be a countermeasure to mitigate a risk, or reduce the impact of a risk factor, or reduce the resources required to mitigate a risk. Such proposals must specify the Countermeasure Readiness Level (CRL) at the beginning of the proposed work and the anticipated CRL at the conclusion of the proposed work.
       3. For technology development objective, the research product should be a technology to mitigate a risk, reduce the impact of a risk factor, or better define a risk or risk factor. Such proposals must specify the Technology Readiness Levels (TRL) at the beginning of the proposed work and the anticipated TRL at the completion of the proposed work.
    3. "As with your Step-1 proposal, the Step-2 proposal must be submitted by your authorized organization representative. The due date and time of submission is 5:00PM ET on November 23, 2015."

## Section D.3

Section D.3 of the NRA: "If a commercial organization wants to receive a grant, cost sharing is required unless the commercial organization can demonstrate that they are unlikely to receive substantial compensating benefits for performance of the work. If no substantial compensating benefits are likely to be received, then cost sharing is not required, but can be accepted. Acceptable forms of cost sharing are discussed in NFS 1816.303-70: http://prod.nais.nasa.gov/cgi- bin/common/wg/mfs.cgi/data/glimpse/archives/63?link=http://prod.nais.nasa.gov:80/far/far0553- nfs0463/1816.htm&file=/data/web/html/far/far0553-nfs0463/1816.htm&line=528#mfs."
At present no substantial compensating benefits for the performance of this work is likely or planned. Any updates to computer hardware or necessary software for accessing Wikiversity resources such as Gene expressions (for this proposal) or the on-going Gene project (sponsored by the commercial organization) will be supplied by the commercial organization. Compensating benefits are supplied for the on-going gene transcription portion of the gene project. Information from this endeavor will be used to guide inquiries into various databases including those of NASA to obtain necessary information for the successful completion of the proposal.

## Section E.2

Section E.2 of the NRA: "The three types of objectives listed in section B.2 of this document give rise to three types of research products. If applicable for the specific research topic, proposers will identify, through answers to questions prompted by NSPIRES, which of the three types of research products best characterizes the proposed research:"
* For the quantification of a crew health and performance risk objective, the research product should define the likelihood or the consequence of a risk more completely. Such proposals must specify how much the uncertainty in the likelihood or the consequence of the risk is anticipated to be reduced by the proposed research.
* For the countermeasure development objective, the research product should be a countermeasure to mitigate a risk, or reduce the impact of a risk factor, or reduce the resources required to mitigate a risk. Such proposals must specify the Countermeasure Readiness Level (CRL) at the beginning of the proposed work and the anticipated CRL at the conclusion of the proposed work.
* For technology development objective, the research product should be a technology to mitigate a risk, reduce the impact of a risk factor, or better define a risk or risk factor. Such proposals must specify the Technology Readiness Levels (TRL) at the beginning of the proposed work and the anticipated TRL at the completion of the proposed work.

## Section E.3

"Step-2 proposals are due by the due date and time listed in Section H of this document. Step-2 proposals will be accepted from invited proposers only. Invited Step-2 proposals must be submitted through the NSPIRES system. The scope and content of invited Step-2 proposals will be limited and complementary to Step-1 proposals; see Section e below for additional details."
"The NSPIRES system will guide proposers through submission of all required proposal information. Select prior-phase proposal when creating an invited Step-2 proposal. The Step-2 proposal must be consistent with the funding entity selected (Omnibus in this case) when submitting the Step-1 proposal. Please note that the Proposal Summary, Business Data, Budget, and Proposal Team and Program Specific Questions are required Cover Page Elements for all Step-2 proposals. The proposal summary should be between 100-300 words (4000 characters maximum) and understandable by the layman reader. In addition to the Cover Page online budget forms, proposers are encouraged to provide expanded budgets as needed (i.e., subcontracts) as part of their budget justification (see number 11 below and the Guidebook for proposers). For proposals with NASA civil servant team members only: Proposers are required to enter the NASA civil servant team member name and fraction of full-time equivalent (FTE) involvement in the same field under the Item column in section F, Other Direct Costs, of the online budget. The funds requested should be entered as the Total Requested Funds for the NASA civil servant, including salary, fringe, materials, travel, etc. (see the FAQ posted alongside this document for additional budget instruction). This budget entry should be made for each year of NASA civil servant involvement, and is in addition to the agency identification under the team member section and the NASA civil servant FTE designation under the business data section."
"To ensure proper Step-2 proposal transmission, please provide only one PDF attachment upload ordered as below. For proposal sections 2 through 8 and sections 16 through 17, specific instruction are given in this NRA (see section D.4.a though D.4.g). These specific instructions supersede those found in the NASA Guidebook for Proposers. Proposals that do not conform to these requirements may be declared noncompliant and declined without review. For sections 1 and sections 10-15, proposers are encouraged to reference the NASA Guidebook for Proposers; however, there are no specific submission compliance requirements for these sections (format, structure, page counts, etc.).
* Table of Contents
* If applicable, inclusion of the Flight Experiment Resource Worksheet, Analog Study Resource Worksheet, or Retrospective Data Request Study Feasibility Assessment Form (see HERO Overview posted on NSPIRES alongside this NRA).
* Software Sharing Plan, if applicable (see HERO Overview posted on NSPIRES alongside this NRA).
* Animal Care or Human Subjects certifications, if applicable (see E.3.a below).
* Response to prior review, if applicable (see E.3.b below).
* Productivity of currently funded research, if applicable (see E.3.c below).
* Vertebrate Animal Scientific Review, if applicable (see E.3.d below).
* Step-1 Carry-Over (See E.3.e below).
* Scientific or Technical Project Description (see section E.3.f below).
* References and Citations.
* Management Approach (see Guidebook for Proposers).
* Personnel CVs (see Guidebook for Proposers).
* Current and Pending Support (see Guidebook for Proposers).
* Facilities and Equipment (See E.3.g below).
* Budget Justification of Proposed Costs (see Guidebook for Proposers).
* Letters of Collaboration or Support (see Guidebook for Proposers).
* Appendices or Reprints (See E.3.h below)."
"While the NSPIRES system allows for the upload of supporting documents as separate uploads, please provide the information above in only one PDF proposal document upload. It is essential that all PDF files generated and submitted meet NASA requirements. At a minimum, it is the responsibility of the proposer to:
1) ensure that all PDF files are unlocked and that edit permission is enabled – this is necessary to allow NSPIRES to concatenate submitted files into a single PDF document; and 2) ensure that all fonts are embedded in the PDF file and that only Type 1 or TrueType fonts are used. In addition, any proposer who creates files using TeX or LaTeX is required to first create a DVI file and then convert the DVI file to Postscript and then to PDF.
See http://nspires.nasaprs.com/tutorials/PDF_Guidelines.pdf for more information on creating PDF documents that are compliant with NSPIRES."
"There is a recommended 10 MB size limit for proposals (Section 2.3(c) of the NASA Guidebook for Proposers). Large file sizes can impact the performance of the NSPIRES system. Most electronically submitted proposals will be less than 2 MB in size."
"NSPIRES accepts electronic proposals through a combination of data-based information (e.g., the electronic Cover Page) and the uploaded PDF file that contains the proposal as outlined above. The NSPIRES proposal submission process ensures that a minimum set of required proposal cover page fields are completed. Provision of the proposal summary and business data elements of the cover page will be necessary in order for the AOR to submit the proposal to NASA. If either of these two proposal elements is incomplete, the "View Proposal/ Check Elements" function of NSPIRES will display red "error" flags and messages to alert the user to the information that is required but missing, and the "Submit Proposal" button will not be available. Although the PI will be able to release the proposal to the AOR, the proposal cannot be submitted by the AOR to NASA until these required fields are complete. Any additional information that is missing will be identified by yellow "warning" flags. Proposers are reminded to check the solicitation instructions to ensure compliance with all instructions, as adherence to these two element validation checks alone is insufficient to guarantee a compliant proposal. Additionally, in those cases where instruction in the NRA contradicts an NSPIRES warning, the NSPIRES yellow “warning” may be ignored. Proposers should follow the NRA instructions closely to help ensure submission of a compliant proposal."
"The NSPIRES system is limited in the character sets that can be used in filling out on-line forms. Please refer to the on-line tutorials when using special characters. Alternatively, spell out special characters where possible (such as micro rather than the Greek symbol). Applicants are encouraged to preview their proposal prior to releasing the proposal to their designated Organization by clicking the “Generate” button at the bottom of the View Proposal Screen in NSPIRES. The “Generate” feature allows applicants to preview their entire proposal in a single PDF file prior to submittal, but it is not a required step in the submission process. Please contact the NSPIRES Help Desk for assistance with this feature (e-mail nspires-help@nasaprs.comor by Telephone to 202-479-9376)."

## Step 2 submittals

The step 2 submittal process consists of two parts:
* release of the step 2 proposal by the PI to the exploratory organization and
* submittal of the step 2 proposal by the exploratory organization to NASA through NSPIRES.
The following proposal has been released to [Marshallsumter's exploratory organization]. Please review it and submit it to NASA as appropriate.
All Team Members, including Co-PI(s), must establish an organizational relationship in order to submit a proposal to NASA.
Additionally, any Team Member with the role of Co-PI must have a confirmed affiliation with the submitting organization. This is also a requirement for proposal submittal to NASA.
To log in to NSPIRES, click on this link: http://nspires.nasaprs.com/
If the above URL is not an active link, please cut and paste the entire URL into your web browser. If you have questions or problems regarding this, or any other NSPIRES business, please contact the NSPIRES Help Desk:
This message is being sent from an outbound-only mail server. Please do not reply to this message.
The following proposal has been submitted for consideration of an award by NASA:
Proposal Number: 15-15Omni2-0008
Proposal Title: Gene expressions in human exploration beyond low earth orbits
Submitting Organization: [Marshallsumter's exploratory organization]
Authorized Organization Representative: Marshallsumter
Principal Investigator: Marshallsumter
Date submitted: 11/20/2015 18:33:24
To log in to NSPIRES, click on this link : http://nspires.nasaprs.com/
If the above URL is not an active link, please cut and paste the entire URL into your web browser.
If you have questions or problems regarding this, or any other NSPIRES business, please contact the NSPIRES Help Desk:
This message is being sent from an outbound-only mail server. Please do not reply to this message.

## Phase 2 results

The evaluation of Phase 2 proposals was concluded on April 16, 2016. Results were announced on April 29, 2016.
"NASA's Human Research Program and the National Space Biomedical Research Institute (NSBRI) will fund 27 proposals to help answer questions about astronaut health and performance during future long duration missions beyond low Earth orbit. The selected proposals will investigate the impact of the space environment on various aspects of astronaut health, including visual impairment, behavioral health and performance, bone and muscle loss, cardiovascular alterations, human factors and performance, sensorimotor adaptation and the development and application of smart medical systems and technologies. All of the selected projects will contribute towards NASA’s long-term plans, such as those planned for the journey to Mars."
"The selected proposals are from 19 institutions in 11 states and will receive a total of approximately $12 million during a one- to three-year period. The 27 projects were selected from 131 proposals received in response to the research announcements entitled, "Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions" and “NASA’s Human Research Program Artificial Gravity Opportunity.” Science and technology experts from academia, government and industry reviewed the proposals. NASA will manage 20 of the projects and NSBRI will manage seven. Ten of the investigators are new to both organizations, and two of the selected projects will be jointly funded by the Human Research Program and NASA’s Space Biology Program."
"The complete list of the selected proposals, principal investigators and organizations is below:"
* Dr. Michael Bailey, University Of Washington, Seattle, “A Phantom and Test Bed to Enhance Kidney Stone Comminution by Therapeutic Ultrasound”
* Dr. Laura Barger, Brigham and Women's Hospital, “Environmental Factors Associated with Sleep Deficiency During Spaceflight”
* Dr. Laura Barger, Brigham and Women's Hospital, “The Impact of Objectively Measured Sleep Deficiency and Circadian Misalignment on Performance During Spaceflight”
* Dr. Silvia Blemker, University of Virginia, “Development of a Muscle Adaptation in Space-Flight Simulator”
* Dr. Susan Bloomfield, Texas A&M University, “Mitigating Radiation-Induced Bone Loss via Dietary Modulation of Inflammatory Cytokines”
* Dr. Lung-Chi Chen, New York University School of Medicine, “Adverse Cardiopulmonary Effects of Exposure to Extraterrestrial Dusts - Implications for Space Travel”
* Dr. Christopher Ethier, Georgia Institute of Technology, “VIIP Simulations of CSF, Hemodynamics and Ocular Risk”
* Dr. Karen Feigh, Georgia Institute of Technology, “Objective Function Allocation Method for Human-Automation/Robotic Interaction using Work Models that Compute”
* Dr. Stephen Fiore, University Of Central Florida, “Macrocognition in Teams: Examining and Developing Team Cognitive Processes and Products in the Context of Long Duration Exploration Missions”
* Dr. Ute Fischer, Georgia Institute of Technology, “Understanding Key Components of Successful Autonomous Space Missions”
* Dr. Charles Fuller, University of California, Davis, “Partial-Gravity Dose Response: Roles of Vestibular Input and Sex in Response to Artificial Gravity”
* Dr. Jeffrey Hoffman, Massachusetts Institute of Technology, “Quantifying and Preventing EVA Injury in Exploration Environments”
* Dr. Vera Khokhlova, University Of Washington, Seattle, “Development and Validation of Therapeutic Ultrasound for Bloodless Surgery in Clinical Simulation in an Analog Environment”
* Dr. Steve Kozlowski, Michigan State University, “Team Cohesion Monitoring Badge: Development of Galvanic Skin Resistance Modality”
* Mr. David Martin, NASA Johnson Space Center, “Autonomous Diagnostic Imaging Performed by Untrained Operators Using Augmented Reality as a Form of ‘Just-in-Time’ Training”
* Dr. Christopher Mason, Weill Medical College of Cornell University, “An Integrated Framework for Characterization of the Noncoding Genome and Epigenome in Astronauts”
* Dr. Anne McLaughlin, North Carolina State University, “Creating a Taxonomy of Variables Affecting Cognitive Aid Design via an Investigation of Hybrid Aids”
* Dr. Jeevan Perera, NASA Johnson Space Center, “NextGen Crew Countermeasure Software for Exploration Mission Support”
* Dr. Lori Ploutz-Snyder, NASA Johnson Space Center, “Gravitational Dose and Multi-System Physiologic Response”
* Dr. Brinda Rana, University Of California, San Diego, “Identification of Functional Metabolomic Profiles Contributing to Physiological Adaptations to Simulated Spaceflight”
* Dr. Seward Rutkove, Beth Israel Deaconess Medical Center, “Musculoskeletal Response to a Partial-Gravity Analog in Rats: Structural, Functional and Molecular Alterations”
* Dr. Ann-Sofie Schreurs, NASA Ames Research Center, “Candidate Nutritional Countermeasure to Mitigate Adverse Effects of Spaceflight”
* Dr. Guillaume Spielmann, Louisiana State University, “The Impact of Long Duration Spaceflight on the Function of B-cells and Biomarkers of Inflammation”
* Dr. Michael Stenger, NASA Johnson Space Center, “Impact of +Gz and -Gz Induced Fluid Shifts on Ocular and Cerebral Parameters during Simulated Orion Re-Entry”
* Dr. Scott Tannenbaum, The Group for Organizational Effectiveness, “A Multi-Faceted Approach to Examine Team Adaptation and Resilience within Isolated, Confined, and Extreme Environments”
* Dr. Ashley Weaver, Wake Forest University, “Quantitative CT and MRI-based Modeling Assessment of Dynamic Vertebral Strength and Injury Risk Following Long-Duration Spaceflight”
* Dr. Steven Yule, Brigham and Women's Hospital, “Developing and Validating Specific Medical Event Management Training Protocols for Flight Crews on Deep Space, Long-Duration Space Exploration Missions”.
Comment - 14 males and 13 females as proposal recipients is good! Very close to 50 %!

### Previous grantees and proposals for twin study

During the State of the Union address to Congress by President Obama on 20 January 2015, astronaut Scott Kelly was introduced. He took part in a year long study involving his twin brother, astronaut Mark Kelly. Scott served on the International Space Station for 340 days since 27 March 2015 while Mark remained on Earth.
The following 10 selected proposals from 10 institutions in 7 states receive a combined $1.5 million during a three-year period:
* Emmanuel Mignot, Stanford University School of Medicine, HERO Twin Astronaut Study Consortium (TASC): Immunome Changes in Space
* Michael Snyder, Stanford University, HERO Twin Astronaut Study Consortium (TASC) Project: Longitudinal integrated multi-omics analysis of the biomolecular effects of space travel
* Brinda Rana, University of California, Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts
* Susan Bailey, Colorado State University, Differential effects on telomeres and telomerase in twin astronauts associated with spaceflight
* Fred Turek, Northwestern University, HERO Twin Astronaut Study Consortium (TASC) Project: Metagenomic Sequencing of the Bacteriome in GI Tract of Twin Astronauts
* Andrew Feinberg, Johns Hopkins University School of Medicine, Comprehensive whole genome analysis of differential epigenetic effects of space travel on monozygotic twins
* Christopher Mason, Weill Medical College of Cornell University, The Landscape of DNA and RNA Methylation Before, During, and After Human Space Travel
* Mathias Basner, University of Pennsylvania School of Medicine, HERO Twin Astronaut Study Consortium (TASC) Project: Cognition on Monozygotic Twin on Earth
* Stuart Lee, Wyle Laboratories, Metabolomic And Genomic Markers Of Atherosclerosis As Related To Oxidative Stress, Inflammation, And Vascular Function In Twin Astronauts
* Scott Smith, NASA Johnson Space Center, Biochemical Profile: Homozygous Twin control for a 12 month Space Flight Exposure

### Subsequent grantees and proposals for twin study

* Susan Bailey, Colorado State University, Fort Collins: Telomeres and the one-year mission project
* Mathias Basner, University of Pennsylvania, Philadelphia: Temporal nature of cognitive and visuospatial brain domain changes during long-duration low-Earth orbit missions
* Marjan Boerma, University of Arkansas, Little Rock: Gamma-tocotrienol as a countermeasure against high-energy charged particle-induced carcinogenesis, cardiovascular disease, and central nervous system effects
* Mary Bouxsein, Beth Israel Deaconess Medical Center, Boston: Dose-response study of musculoskeletal outcomes following centrifugation in adult mice on the International Space Station and Time course of spaceflight-induced adaptations in bone morphology, bone strength and muscle quality
* Meghan Downs, NASA’s Johnson Space Center, Houston: Temporal changes in astronauts’ muscle and cardiorespiratory physiology pre, during, and post spaceflight
* John Edwards, New York Medical College, Valhalla: Countermeasures to radiation-induced cardiomyopathy
* Christine Fanchiang, Space Research Company, Boulder, Colorado: Using a human capabilities framework to quantify crew task performance in human-robotic systems
* Charles Fuller, University of California, Davis: Adaptation of mouse systems physiology to artificial gravity via centripetal acceleration: timing, metabolism and aging
* Alan Hargens, University of California, San Diego: Self-generated lower body negative pressure for deep-space missions
* John Lee, University of Wisconsin, Madison: Conversation analysis to measure and manage trust in virtual assistants
* Brandon Macias, NASA’s Johnson Space Center: Investigating structure and function of the eye
* Jessica Marquez, NASA’s Ames Research Center, Moffett Field: Crew autonomy through self-scheduling: guidelines for crew scheduling performance envelope and mitigation strategies
* Jason Norcross, NASA’s Johnson Space Center: Validation of fitness for duty standards using pre- and post-flight capsule egress and suited functional performance tasks in simulated reduced gravity
* Millard Reschke, NASA’s Johnson Space Center: Neuro-vestibular examination during and after spaceflight
* Kanokporn Rithidech, State University of New York at Stony Brook: Countermeasures against adverse effects of space radiation
* Stephen Robinson, University of California, Davis: Enabling autonomous crew task performance with multimodal electronic procedure countermeasures
* Stephen Romaniello, Arizona State University, Tempe: Evaluating resistive exercise as a long-term countermeasure for spaceflight-induced bone loss using calcium isotopes
* Debra Schreckenghost, TRACLabs, Webster, Texas: Enhancing situation awareness of automated procedures using adaptive multimodal augmented reality displays
* Daniel Selva, Texas A&M University, College Station: Virtual assistant for spacecraft anomaly treatment during long duration exploration missions
* Mark Shelhamer, Johns Hopkins University, Baltimore: Assessment of otolith function and asymmetry as a corollary to critical sensorimotor performance in missions of various durations
* Leia Stirling, Massachusetts Institute of Technology, Cambridge: Responsive multimodal human-automation communication for augmenting human situation awareness in nominal and off-nominal scenarios
* Martha Vitaterna, Northwestern University, Evanston, Illinois: Impact of the martian solar day and gravity on microbiota in mice: mechanisms and multi-system physiology
* David Zawieja, Texas A&M University Health Science Center, Temple: Effects of microgravity on ocular vascular hydrodynamics
* Quan Zhang, Massachusetts General Hospital, Charlestown: Characterizing the baselines of sleep quality, cognitive / operational performance, immune function, and intracranial fluids for deep space expeditions
"NASA's Human Research Program and Space Biology Program will fund 25 proposals to help answer questions about astronaut health and performance during future long-duration missions beyond low-Earth orbit. The selected proposals will investigate biological, physiological, and behavioral adaptations to spaceflight. All of the selected projects will contribute to NASA’s long-term plans, which include human missions to the Moon and Mars."
"The Human Research Program works to address the challenges of spaceflight that impact astronaut health, and its research may provide knowledge and technologies that could improve human health and performance during space exploration and aid the development of potential countermeasures for problems experienced during space travel. The Space Biology Program seeks to understand causal cellular and other mechanisms that underlie adaptation to fractional gravity levels in cells, microorganisms, plants, and animals."
"NASA is laying the groundwork for future one-year exploration missions on the International Space Station. Researchers and scientists were asked to submit proposals that considered a robust program that could include as many as 30 astronauts: 10 to conduct shorter missions of up to two months, 10 as part of standard six-month missions, and 10 one-year missions in space. By using missions of varying length, NASA seeks to establish profiles of human physiological, behavioral, and psychological variables of importance for ensuring astronaut health and performance during future long-duration deep space missions. The selected investigations cover a variety of physiological systems including the brain, eyes, sensorimotor, cardiovascular, musculoskeletal, bone, and immune. In addition to the studies NASA selected, partner space agencies from Canada, France, and Germany will contribute several experiments to the project."
"With information gained from the selected studies, NASA aims to address five hazards of human space travel: space radiation, isolation and confinement, distance from Earth, gravity fields (or lack thereof), and hostile/closed environments that pose great risks to the human mind and body in space. Among the selected projects, topics include investigating biological, physiological, and behavioral functions of rodents during partial gravity exposures provided by centrifugation on the space station, studying vision problems in astronauts, identifying medical countermeasures to space radiation, and developing real-time human performance support for autonomous spaceflight."
"The selected proposals are from 19 institutions in 11 states and will receive a total of approximately $30.5 million during a two- to seven-year period. One investigator is leading two different studies, and six investigators are new to the Human Research Program. The 25 projects were selected from 100 proposals received in response to the 2017 Human Exploration Research Opportunities Appendix C. Science and technology experts from academia, government, and industry reviewed the proposals."

### Translational Research Institute for Space Health subsequent grants and awardees

"The Translational Research Institute for Space Health (TRISH), in partnership with NASA through a cooperative agreement to fund transformative human health technologies to predict, protect, and preserve astronaut physical and mental wellness during deep space exploration missions, has selected 15 new biomedical research projects."
"The newest wave of awardees will develop solutions that will solve the highest priority risks to human health and performance during deep space missions. Topic areas include drug-free optimization of human performance; artificial intelligence and predictive algorithms of health, behavior, and medical events; novel shielding materials for preserving medications; radiation countermeasures; and multi-purpose edible plants for spaceflight applications. During the two years in which they will be funded, the awardees will be tasked with delivering groundbreaking investigative research in these areas to protect human health in space."
"The selected award recipients for the annual Biomedical Research Advances for Space Health (BRASH) 1801 solicitation are as follows:"
* Photobiomodulation to ameliorate neuronal degeneration and cognitive decline after mixed field irradiation University of Arkansas for Medical Sciences, Little Rock Antino Allen, Ph.D.
* Performance enhancement through multi-modal stochastic resonance University of Colorado, Boulder Allison Anderson, Ph.D.
* Advanced algorithms for the prediction of adverse cognitive and behavioral conditions in space University of Pennsylvania School of Medicine, Philadelphia Mathias Basner, M.D.
* miRNA signature detection and countermeasures against HZE radiation exposure for tissue degeneration NASA’s Ames Research Center, Mountain View, California Afshin Beheshti, Ph.D.
* Gene therapy countermeasures for detrimental effects of space radiation Duke University School of Medicine, Durham, North Carolina Dawn Bowles, Ph.D.
* Nucleic acid therapy platform for real-time countermeasures during spaceflight missions University of Colorado, Boulder Anushree Chatterjee, Ph.D.
* Co-optimization of duckweed biomass, nutritional quality and input-use efficiency University of Colorado, Boulder Barbara Demmig-Adams, Ph.D.
* Evaluation of SmartSleep technology for improving the efficiency and restorative quality of sleep in healthy adults in order to mitigate cognitive performance deficits due to sleep restriction and emergency awakenings University of Pennsylvania School of Medicine, Philadelphia David Dinges, Ph.D.
* Boosting brain metabolism in spaceflight with transcranial photobiomodulation City College of New York, New York Jacek Dmochowski, Ph.D.
* Genetically minimizing non-edible portions of plants for spaceflight applications University of California, Riverside Robert Jinkerson, Ph.D.
* Silk composite biomaterials for shielding medications in space Tufts University, Medford, Massachusetts David Kaplan, Ph.D.
* Integrative personalized omics profiling next steps: detection and classification of deviations from wellness Michigan State University, East Lansing George Mias, Ph.D.
* Safety and efficacy of an accelerated protocol of intermittent theta burst transcranial magnetic stimulation (TMS) to enhance performance and promote resilience in astronauts Medical University of South Carolina, Charleston Donna Roberts, M.D.
* OASIS: Optimizing Auditory Stimulation to Improve cognitive performance using SmartSleep University of Wisconsin, Madison Giulio Tononi, M.D., Ph.D.
* Wearable modular focused ultrasound systems for non-invasive stimulation of the human brain during deep space exploration Brigham and Women's Hospital, Boston, Massachusetts, Seung-Schik Yoo, Ph.D.
"The Translational Research Institute for Space Health is funded through a cooperative agreement from NASA to Baylor College of Medicine with consortium partners California Institute of Technology and Massachusetts Institute of Technology."
"TRISH is closely partnered with the NASA Human Research Program and strives to recruit new investigators and fund new approaches to solve challenges faced by humans in deep space. Ten of the 15 investigators funded in this round are new to this community of scientists."

## Panel Review
### Proposal Summary (as provided by the PI)

The objective of this proposal is to explore each avenue of the Human Research Roadmap to determine gene suites that may be contributing to or causing these effects or increasing risks of these effects sufficiently to impair astronaut functioning. Even normal (Earth-based) gene expression may be producing physiological and performance effects from the hazards mentioned. Under, or over expression, of genes in each suite may alter gene expression sufficiently to reduce adverse effects. Altered expression of genes from each suite in preparation for return to normal (Earth-based) environments may reduce hazards before return to Earth.

### Significance (strengths and weaknesses)

Does this study address one or more risks and associated gaps in the Human Research Program Integrated Research Plan? Does the study test a significant hypothesis or produce data that would enable a significant hypothesis to be generated? If the study is non-hypothesis driven, are the data produced needed to understand or reduce the risk to crew health or performance? If the task will produce a software model, new technology, new procedure or new tool, how will it serve to better quantify or mitigate a risk? If the aims of the application are achieved, how well will the product(s) address the risk(s)? If the aims of the application are achieved, how will scientific knowledge or technology advance?
This study will generate a list of candidate genes and their regulatory elements that have been previously/potentially associated with space travel risks, which is unlikely to provide new information for advancing our understanding or reducing the risks to crew health or performance.

### Approach (strengths and weaknesses)

Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Is the proposed approach likely to yield the desired results? Does the applicant acknowledge potential problem areas and consider alternative tactics? If applicable, has the applicant included a range of reasonable sample sizes for a proposed study with proper justification?
Specific to one year studies: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Is the proposed approach likely to yield the desired results in one year? Does the applicant acknowledge potential problem areas and consider alternative tactics?
The investigator tries to explore the different avenues of the Human Research Roadmap to discover the links between gene changes and the space-travel-related physiological issues, by mostly web search and literature studies. However, a systemic study plan is lacking and based on the examples described in the application, some of the searches were not conducted in appropriate databases and/or with appropriate terms.
Comment - the NASA GeneLab database contains two papers on possible human genes involved in spaceflight medical problems. NCBI Gene is the World's largest repository (PubMed) for medical research including genes and their modulation. Terms chosen from the Human Research Roadmap succeeded in isolating applicable or potentially applicable genes, which current and planned NASA research is not exploring. The systematic study plan was indicated. Demonstrated familiarity with NCBI is the key.

### Statistical Plan (strengths and weaknesses)

Does the study provide adequate justification for sample size? For example, is the choice of primary outcome relevant for the stated Aims? Are assumed effect magnitudes reasonable? Are assumed variability estimates reasonable? Are they estimated properly? Are they relevant for the proposed experimental design and data analysis methodology? What Type I and Type II errors are assumed? Is there room for a tradeoff here to accommodate sample size constraints and still provide useful information from the study? Do the investigators provide a reasonable data analysis plan? For example, is it appropriate for the proposed experimental design (e.g. repeated measures)? Does it address research hypotheses or aims? Is it robust to the sampling and other constraints associated with the research venue?
The investigator did not propose any plan for using the reported significance levels to aid in the selection of the candidate genes.
Comment - the plan was not recognized by the reviewers as a double-blind study. Significance levels can not be assigned.

### Risk Mitigation (strengths and weaknesses)

Does the study adequately improve the understanding of the adverse consequences, the probability of its occurrence, or the timeframe in which the risk must be addressed? Will the proposed countermeasure reduce a risk to crew health or performance, reduce the impact of the risk or reduce the resources required to mitigate it? Will the research product reduce the risk to crew health or performance, reduce its impact or better define it and is the technology feasible within the confines of the operational environment?
The products of this study are unlikely to have direct impact on advance our understanding or reducing the risks to crew health or performance.
Comment - it's too soon for direct impact! The first gene found GeneID: 348 apolipoprotein E has never been considered by NASA investigators nor studied on the ISS.

### Investigators (strengths and weaknesses)

Are the investigators appropriately trained and well suited to carry out this work? 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?
The PI, also the sole investigator, lacks appropriate training and expertise in the analysis of gene expression and regulation.

### Environment (strengths and weaknesses)

Does the scientific environment in which the work will be performed contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support?
The PI owns a commercial research/exploration organization, which will provide the computer hardware and necessary software for this project. However, there is no collaborative arrangement with any other investigators, which makes the scientific environment unlikely to contribute to the success of this study.
Comment - review committee did not recognize that the proposed study is a double-blind one.

### Overall Evaluation (overall balance of strengths and weaknesses of the proposal)

In this study, the applicant proposed to generate a list of candidate genes, along with their regulatory elements, that have been previously/potentially associated with each risk listed in the Human Research Roadmap through search in literature and open databases. The products are of low significance, as all the information are already in the literature/databases and no new information will be generated by this study. Also, a systemic plan is lacking and no novel method will be employed. In addition, the investigator lacks the expertise and experience in the analysis of gene expression and regulation, which makes the probability of success of this study to be very low. Therefore, the overall weaknesses identified greatly outweigh the strengths of this study.
Comment - review committee members sampled a number of {{gene project}} resources to hit levels as high as about 1600 during April but not enough checked out Transcription of A1BG which extensively looks at gene expression and regulators in transcription. The new information is the potentially applicable gene suite!

### Cost, Relevance, and Additional Non-Merit Issues

Merit score is not affected by the cost of the proposed work or the relevance of the proposed work. The Panel may include comments concerning the proposal’s budget and relevance.
It is not clear how much effort the PI will dedicate to this study.
Comment - milestones indicated PI would dedicate whatever effort would be needed to accomplish each portion of the Human Research Roadmap.
SCORE DESCRIPTION: NRFC (NRFC: 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.)
Comment - Here below are the only previous review comments.
Result (Phase 1 Review):
* "The review of the Step-1 proposals received in response to the NASA Research Announcement (NRA) NNJ15ZSA001N-OMNIBUS “Human Exploration Research Opportunities” has been completed. Your proposal has been found responsive to the research emphases outlined in the NRA, and you are invited to submit a full Step-2 Omnibus proposal."

## Hypotheses

* A thorough literature search including available NASA documentation may help to indicate those genes or gene suites (in some cases specific isoform expressions) that if altered may reduce these hazards.