Skip to main content

Secretome Analysis of Environmental Nanoparticle Induced Biomarkers


EMSL Project ID
18592

Abstract

A national goal for particulate matter (PM) research centers is to develop biological markers of specific mechanistic pathways that can be used to link findings from animal, human and epidemiological studies [1]. However, their remains much speculation as to the biological activity of nanoparticle exposure as a component of PM stimulation. We propose to test the hypothesis that differences in the signaling pathways stimulated by different types or sizes of PM in macrophages will be reflected by quantitative and qualitative differences in the pattern of proteins secreted from the cell. We propose to develop approaches to globally measure both the abundance and turnover of proteins released from macrophages into the extracellular space, i.e. the "secretome", in response to PM exposure. Our proposed approach will employ metabolically incorporated amino acids labeled with stable isotopes to selectively label newly synthesized proteins which are secreted from macrophages in response to PM exposure. Various mass spectrometry (MS) methods for peptide/protein identification in combination with the accurate mass measurements of Fourier transform ion cyclotron resonance (FTICR) will be used to both identify secreted proteins, as well as measure their synthesis and turnover. This approach will permit measuring the dynamic secretome response at a global scale and determine how this response changes as the chemical constituents and size of PM are systematically varied.

Project Details

Start Date
2006-03-20
End Date
2009-03-22
Status
Closed

Team

Principal Investigator

Jon Jacobs
Institution
Environmental Molecular Sciences Laboratory

Team Members

Brian Thrall
Institution
Pacific Northwest National Laboratory

Susan Varnum
Institution
Pacific Northwest National Laboratory