Measurement of Aberrant Protein Folds in Malignant Cells with Proteomics and Mass Spectrometry


Year of Award:
2017
Award Type:
R33
Project Number:
CA212973-01
RFA Number:
RFA-CA-16-002
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
YATES, JOHN R
Other PI or Project Leader:
Not Applicable
Institution:
SCRIPPS RESEARCH INSTITUTE
Project Summary Malignant transformation of cells drives the development of tumors. Cancer cells can be routinely genotyped today revealing a large number of somatic mutations. However, it remains unclear which mutations contribute to malignant transformation and provide a survival advantage to cancer cells and which are simply passenger mutations. Rather than dissecting each mutation individually by biochemical techniques such as cloning and overexpression, we propose to systematically profile the proteome of cancer cells for altered protein surface accessibility, which can help to better understand the impact of somatic mutations on proteome function and activity. Neomorphic perturbations in protein surface accessibility is revealed with a new, quantitative, in vivo chemical labeling approach coupled to shot gun proteomics. The novel approach can be used as a platform technology to screen patient-derived cancer cells and holds promise to pinpoint critical, cancer cell specific perturbations in the proteome.