Abstract#

ELI5: Astronauts on a long mission face adverse challenges to their bodies: bones get weaker, muscles shrink, radiation damages DNA, and their brains start to slow down. It's like the body is aging really fast. Changes that take decades to occur on Earth, happen within weeks and months in space. We don't yet have good medicines to prevent it.

Some people, though, are naturally tougher: their genes make them more resistant to bone loss, radiation damage, or muscle wasting. The Spacefarer Phenome project wants to find gene variants that confer this resistance, and use them as a roadmap to develop drugs that could protect any astronaut.

The project will use large public databases of human genetic data, run them through a series of computational filters to find the most promising genetic "shields", and then virtually test existing drugs to see if any of them could be repurposed to flip those protective switches. The pipeline will produce a ranked shortlist of drug candidates backed by solid evidence – a first step to a robust astronaut biology.

Problem#

Human physiology evolved for Earth and is poorly suited for deep space. Astronauts face cosmic radiation at 50–500 mSv/year, causing DNA damage, cellular senescence, and elevated cancer risk; 1–2% monthly bone density loss, up to 20% muscle atrophy over six months; and cognitive decline from isolation. The observed changes can be framed as accelerated organismal aging with remarkable overlaps with the established hallmarks of aging framework. Current countermeasures are symptomatic: exercise slows but does not prevent musculoskeletal loss; shielding reduces but cannot eliminate radiation exposure for deep-space missions. A toolbox to systematically identify naturally occurring protective genetic variants across these stressors and to translate them into therapeutic targets is lacking.

Solution#

The Spacefarer Phenome project aims to identify genetic traits that confer resilience and adaptability for space environments. By combining genomics, structural biology, and molecular modeling, we will:

• Identify protective genetic variants

• Prioritize druggable targets for therapeutic development

• Find drugs that could enhance or mimic these variants

This proposal funds a focused, first-pass computational pilot to uncover genetically supported intervention opportunities for human spaceflight resilience. Initially, the project will focus on 1-2 phenotype classes, with final selection informed by data quality and biological relevance. By combining public human genome-wide association studies (GWAS) data, causal inference via Mendelian randomization (MR), and structure-informed prioritization, the project will generate an initial evidence base for space-relevant target discovery and a shortlist of promising compounds for follow-on.

Project deck: https://doi.org/10.6084/m9.figshare.30948245

Benefits#

This project benefits MoonDAO by expanding its activity into an important but underexplored domain of space exploration: human biological resilience. As a focused computational pilot, it will generate tangible public outputs, including a reproducible target-discovery workflow, a prioritized list of genetically supported therapeutic targets, and a shortlist of repurposable compounds for follow-on validation. These outputs give MoonDAO a credible entry point into space biology, help attract contributors from the life sciences and computational research communities, and strengthen the organization's broader mission of enabling sustainable human presence beyond Earth.

By open-sourcing the workflow and key artifacts, the project gives MoonDAO a visible, reusable research asset that can support future collaborations, community engagement, and follow-on scientific work. The methodology, findings, and data generated will be published as a preprint, acknowledging MoonDAO as a funding body. Furthermore, the preprint will become accessible through major science communication platforms, such as Google Scholar, ResearchGate, and ResearchHub, garnering visibility for MoonDAO among space biology/AI domain specialists.

Media plan: MoonDAO will receive recognition upon the funding receipt in a series of social media posts, produced by Expanse Bio (https://expansebio.xyz/), a decentralized space biology initiative, across X, LinkedIn, and Instagram, as well as upon the completion of the project, highlighting key findings in a long-form format, e.g., blog article, which will likewise be disseminated through the mentioned social platforms.

Risks#

This is an exploratory computational discovery project designed to learn efficiently from existing data while building a strong foundation for follow-up work. Acknowledging the scarcity of direct spaceflight datasets, the workflow will prioritize biologically relevant proxy phenotypes supported by large public resources, then refine candidates through causal inference, phenome-wide profiling, and structural prioritization.

Time constraints and project complexity are addressed by refraining from generative steps in favor of drug repurposing strategies, which will reduce the computational load on docking screens and molecular dynamics (MD) simulation.

A methodological risk may lie in biological over-interpretation: human-genetic associations may not automatically translate into safe intervention targets due to the potential pleiotropic nature of some gene variants and, by extension, off-target effects of the discovered interventions. We address this directly by integrating extensive PheWAS (phenome-wide association studies) to computationally profile and score all off-target effects across human phenotypes prior to any structural modeling.

Project updates will be publicly shared with the MoonDAO Senate in a timely fashion.

Objectives#

Objective #1: Generate a prioritized target shortlist for key spaceflight stressors, with full statistical provenance and biological annotation. Key results: A reproducible target prioritization system and benchmarking for 1-2 space-relevant phenotype classes.

Objective #2: Develop a four-stage computational pipeline (GWAS → MR → PheWAS → Druggability) that identifies causally validated, druggable genetic targets for human spaceflight resilience. Key results: A ranked list of 3-5 genetically supported, mechanistically interpretable targets.

Objective #3: Validate target druggability with molecular docking on a small set of drug-like compounds amenable to therapeutic repurposing. Key results: A short list of 20-50 compounds with explicit evidence trails.

Team (Table A)#

Team bios#

Project lead: The project is carried out by Rakhan Aimbetov, Ph.D. in biotechnology, who has academic research and industry experience. His graduate research at MD Anderson Cancer Center (USA) focused on mTOR kinase complex biochemistry; postdoctoral work followed at Institut Gustave Roussy (France) in histone variant epigenetics and proteomics, and at Nazarbayev University (Kazakhstan) in the molecular mechanisms of Parkinson's disease. He has published 5 peer-reviewed studies (2 as first author, 1 as corresponding author). Industry and academic roles include Regulatory Affairs Specialist and Vaccine Portfolio Manager at GlaxoSmithKline, Deputy Department Head for Science and International Cooperation at the Al-Farabi Kazakh National University School of Medicine, and Senior Researcher at the National Center for Biotechnology (Kazakhstan). His molecular biology expertise underpins the biological interpretation and target validation components of this project.

Multisig member #1: Rakhan Aimbetov – biologist; principal investigator, developer. https://www.moondao.com/citizen/rakhan-aimbetov-64

Multisig member #2: Dorian Leger – space bioeconomy expert; founder of Cx Bio (https://www.cxbio.io/), a biotech consultancy, and Expanse Bio (https://expansebio.xyz/), a decentralized space biology initiative. Formerly, Max Planck Institute, ispace, European Space Agency, Tesla. https://www.linkedin.com/in/dorianleger/

Multisig member #3: Michael Mati – aircraft maintenance engineer; DeSci operator and communications/marketing lead at Expanse Bio. Formerly, HydraDAO, CryoDAO. https://www.linkedin.com/in/michael-mati-33b7272a7/

Multisig member #4: Rina Faber – space missions engineering expert; COO at LunCo (https://lunco.space/), MoonDAO senator. https://www.moondao.com/citizen/e-cat-74

Multisig member #5: Ryan Shauers – MoonDAO executive. https://www.moondao.com/citizen/ryan-1

Timeline (Table B)#

Deadline for the project: end of July 2026

Budget (Table C)#