Responsible Center: NSBRI
Solicitation: 2015 NSBRI-RFA-15-01 First Award Fellowships
Grant/Contract No.: NCC 9-58-PF04307
Project Type: GROUND
No. of Post Docs: 0
No. of PhD Candidates: 1
No. of Master's Candidates: 0
No. of Bachelor's Candidates: 0
No. of PhD Degrees: 0
No. of Master's Degrees: 0
No. of Bachelor's Degrees: 0
|| POSTDOCTORAL FELLOWSHIP
Before we can ethically send Astronauts to distant locations in space, such as Mars or asteroids, it is critical that we understand how spaceflight affects the human immune system. For years, post-flight data has suggested that spaceflight has a negative impact on the immune system. Unfortunately, the majority of this data was obtained following short-duration missions after the Astronauts had returned to Earth, meaning that no in-flight data was collected. The recent 'Integrated Immune' study filled many of these knowledge gaps by analyzing blood obtained from Astronauts on the Space Shuttle (or International Space Station (ISS)) while they were still in space. Of particular interest were the findings that anti-viral immune responses were compromised during spaceflight. Consequently, latent viral reactivation can result in many negative consequences including Shingles, reduced vaccine efficacy, and increased susceptibility to infection. While the 'Integrated Immune' study focused primarily on the adaptive immune system, our 'Salivary Markers' flight experiment (Principal Investigator Dr. Richard Simpson) has focused on the innate immune system. The current proposal focuses on Natural Killer (NK)-cells, which are able to kill virally-infected and malignant cells without prior exposure. Our in-flight data shows that NK-cell anti-tumor activity is greatly reduced during spaceflight, while cytomegalovirus (CMV)-driven responses are amplified. The current proposal will explore two plausible mechanisms for these observations--microgravity and stress. The effects of microgravity can be simulated with a rotating wall vessel that keeps the cells in a constant state of freefall, while stress can be simulated using serum (with natural stress hormones) from Astronauts on ISS. It is hypothesized that treatment with simulated microgravity and spaceflight-derived serum will mimic the deleterious effects of spaceflight on NK-cells. Once we have determined the mechanisms underpinning the adverse effects of spaceflight on NK-cells, we can begin to develop countermeasures that will protect future space explorers from becoming immunocompromised during long-duration missions.
Based on data from 10 subjects tested so far, we are able to report that exposure to simulated microgravity (SMG) decreases NK-cell anti-tumor activity similarly to spaceflight. This decrease in function was due to impaired NK-cell degranulation, decreased production of cytotoxic cytokines (e.g., tumor necrosis factor-a and interferon-a), and reduced expression of the cytolytic protein perforin. No change in NK-cell expansion, conjugation with tumor target cells, or NK-cell expression of the pro-apoptotic protein granzyme B was observed. The serum component of the project is just now underway as we only recently received NASA IRB (Institutional Review Board) approval to request an additional blood sample from the Astronauts who participated in our 'Salivary Markers' flight study.