Speaker
Dr
Ravishankar R. Vallabhajosyula
(CFD Research Corporation (CFDRC))
Description
Exposure to space radiation and the associated health risks pose a major challenge to the growth of deep space exploration. The effects of such radiation on electronics and shielding have been studied in considerable detail and have led to novel methods and design strategies for minimizing equipment failure and developing hardening strategies. Similar efforts to better understand the effects of space radiation on human health utilize techniques such as DNA strand breaks, cytogenic analysis and molecular markers, and are often used to measure the late-effects of exposure to radiation. However, these approaches require sophisticated equipment, are typically based on destructive analysis of cells and are time consuming. There is a clear need for the development and validation of the early stage biomarkers of radiation exposure, which could lead to the development of improved therapeutic protectants, targeted drug delivery or other countermeasure or can be used to mitigate the severity of radiation exposure.
In this context, we have developed and validated a systems biology based approach for identifying biomarkers from genomic samples. Our approach integrates features of the detected signaling pathways to construct a comprehensive network model. Cells exposed to different doses of radiation are analyzed for changes in gene expression. The upregulated or downregulated genes are used to automatically build a pathway model integrating diverse mechanism of action. A Boolean logic-based simulation of these complex pathways is used to determine an Active Core Pathway that captures the principal responses of the radiation exposure. Network modeling and analysis is subsequently applied to the cellular pathways to discover and rank biomarkers of radiation exposure. Model predictions are validated is performed by comparing with experimental studies.
This approach can be integrated downstream of currently used software tools that compute dosages and energy-deposition in biological tissue (e.g., Geant4 DNA module) when an astronaut is exposed to radiation. Detection of one or more of the predicted radiation biomarkers of early-exposure can serve as a starting point for application of relevant therapeutics or countermeasures.
Primary author
Dr
Ravishankar R. Vallabhajosyula
(CFD Research Corporation (CFDRC))
Co-authors
Dr
B. Prabhakarpandian
(CFD Research Corporation (CFDRC))
Ms
Giuseppina Lamberti
(Temple University)
Dr
Kapil Pant
(CFD Research Corporation (CFDRC))
Dr
Mohammad Kiani
(Temple University)
Dr
Mohan Achary
(Temple University)
