Global mass spectrometry-based analysis of covalent modifications in proteomes after radiation
Abstract
Ionizing radiation (IR), including X-rays and ? radiation produced by radioactive materials, damages all cellular biomolecules. Most of this damage is inflicted via chemical changes of cellular components caused by radiation-induced alterations of water to produce the highly reactive moieties known as hydroxyl radicals. An improved understanding of how cells deal with gamma radiation is currently limited by the lack of information about the specific type and levels of damage that the reactive molecules induce in cellular proteins. Using state of the art technologies involving instruments known as mass spectrometers that precisely determine the identity and amount of modified proteins, we will deliver a comprehensive analysis of gamma radiation-induced damage to all of the proteins within a cell. This analysis will be both chemically precise and quantitative. We will focus initially on the simple and well-characterized experimental model organism Escherichia coli. We will then expand the effort to take advantage of a bacterium, called Deinococcus radiodurans, that can survive doses of ionizing radiation a thousand or more times greater than that known to be lethal to mammals. We will define the proteins and parts of proteins most sensitive to ? radiation-induced damage and correlate those covalent changes with cell death, in the process probing the mechanisms used by Deinococcus to survive a high radiation environment. The study will ultimately allow similar methods to be applied to human cells to produce a catalogue of radiation damage to our cellular proteins. This study is one essential prelude to efforts designed to discover new drugs and other means of ameliorating the effects of radiation on workers and organisms exposed to high radiation environments.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 13, 2016
- Source ID
- HDTRA11610049
Entities
People
- Michael Sussman
Organizations
- Defense Threat Reduction Agency
- University of Wisconsin–Madison