Task Fundamental Biological studies of protein phosphorylation profiles after HZE exposure (Completed)
Last Published:  11/23/20 11:55:12 AM (Central)
Short Title: Protein PP
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Space Biology Program
Funding Status: Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
Solicited
Aims:
  1. We propose to establish in vivo molecular response profiles to HZE exposure and bystander effects, whereby these complex variables will inherently be accounted for by measuring the resulting cellular manifestations. Within minutes of ionizing radiation exposure, a number of phosphorylation events occur, orchestrating cellular signaling pathways critical for cell survival, homeostasis, and genomic stability, thus determining the ensuing fate of cells after damage.
  2. We will detail phosphorylation events after Fe ion exposure to establish a molecular profile of the biological response to this particularly relevant HZE particle.
  3. Standard immunofluorescence microscopy and a novel fluorescence activated cell sorter (FACS) based assay will be used to quantitiate phosphorylation levels. The FACS based assay is a non-subjective, relatively rapid method capable of quantitating phosphorylation levels in specific phases of the cell cycle, making it ideal for these studies.
  4. Profiles of molecular markers, phosphorylated in response to Fe ion and X-ray exposure will be compared at various times to DNA repair, cell cycle progression and ultimately survival.
  5. Bystander effects, which are effects occurring in cells not directly exposed to radiation, could account for a substantial part of the total risk associated with space irradiation. Therefore, it is essential to define molecular phosphorylation profiles in response to high and low LET induced bystander effects for accurate risk assessment. These profiles will be compared to each other and to direct exposure profiles to determine unique characteristics associated with these different stimuli, and to establish quantifiable endpoints for the bystander effect.
  6. To identify potential countermeasures, we will also test whether addition of anti-oxidants diminishes the observed direct radiation and bystander effects. Different tissues of the body are known to respond differently to ionizing radiation; the effects of HZE in this regard are not well understood.
  7. We will use two tissue representative cell types, fibroblasts and lymphocytes, to determine the universality of the molecular phosphorylation profiles.
  8. Lastly, we will take advantage of rapidly advancing studies to develop novel phospho-specific antibodies to a lymphocyte specific protein.
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RiskRisk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
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RiskRisk of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure and Secondary Spaceflight Stressors
You are here!TaskFundamental Biological studies of protein phosphorylation profiles after HZE exposure

RiskRisk of Radiation Carcinogenesis
You are here!TaskFundamental Biological studies of protein phosphorylation profiles after HZE exposure