Responsible Center: NASA ARC
Grant Monitor: Griko, Yuri
Center Contact: 650-604-0519
Yuri.V.Griko@nasa.gov
Unique ID: 15945
|
Solicitation / Funding Source: 2022 Space Biology NNH22ZDA001N-SBR: E.9 Space Biology Research Studies
Grant/Contract No.: 80NSSC24K0744
Project Type: GeneLab,GROUND
Flight Program:
|
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
|
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
|
| Task Description: |
The objective of this proposal is to determine if exposure to lunar dust simulant will alter the characteristics of human intestinal cells and intestinal-relevant bacteria, both independently and during their interactions – in ways that could increase health risks. We will further evaluate if the combination of both lunar dust simulant and low shear modeled microgravity (LSMMG) culture of intestinal-associated bacteria could further alter their characteristics and interactions with human intestinal cells. We hypothesize that exposure to lunar regolith simulant will alter the phenotypic and molecular genetic characteristics of both human intestinal cells and intestinal-relevant bacteria. We further hypothesize that culture of a model enteric bacterial pathogen under LSMMG conditions, in combination with lunar dust simulant, will exacerbate the alterations observed for either stressor alone. To retain applicability of these findings for spaceflight applications, all microorganisms selected for this study have a direct route of access to the astronaut intestine (e.g., through food, water, air), and include isolates from the International Space Station (ISS) and other organisms with clear relevance to crew health.
Proposed Aims:
Aim 1. Characterize the impact of lunar dust simulants on the viability and pathobiology of 3-D biomimetic models of human intestine. Cytotoxicity, pathology, and inflammatory responses of 3-D models of human intestine will be profiled in the presence and absence of lunar dust simulants.
Aim 2. Characterize the impact of lunar dust simulants on phenotypic characteristics of pathogenic and commensal microorganisms associated with human spaceflight and the intestine.
Aim 2a: A high throughput screening approach will be applied using multi-well plates to profile a panel of intestinal-relevant bacteria (pathogens and commensals) for alterations in growth/viability in response to challenge with lunar dust simulants.
Aim 2b: The model enteric pathogen Salmonella typhimurium (S. typhimurium) will also be profiled for alterations in growth, acid resistance, and biofilm formation in response to the combined impact of dust simulants and LSMMG culture.
Aim 3. Characterize the impact of lunar dust simulants on the viability and pathobiology of 3-D biomimetic models of human intestine following challenge with a model enteric pathogen. Susceptibility of 3-D models to infection will be evaluated using S. typhimurium, a model pathogen previously shown to exhibit spaceflight – and LSMMG-induced alterations in virulence, 3-D intestinal infection profiles, pathogenesis-related stress responses, and multi-omics profiles. S. typhimurium will be cultured under LSMMG (with and without simulants) prior to addition to the 3-D model (with/without simulants). Cytotoxicity, inflammatory responses, colonization, and dual RNA sequencing (RNA-seq) of the host-pathogen interaction will be performed. We will also transcriptionally profile LSMMG-cultured S. typhimurium just prior to infection. |
Home
Developed and operated by: NASA Research and Education Support Services