Project Leads: Robert Moritz, Jeff Ranish

The quantitative, sensitive and comprehensive measurement of proteins and their interactions remains a significant challenge for proteomics. Yet such measurements are critical to developing predictive models of protein-based network structures, and the dynamics that underlie biological responses.  The research projects drive the development of: 1) comprehensive quantitative measurements of proteomes and sub proteomes, lipidomes, metabolomes, post-translational modifications, protein/protein or nucleic acid/protein interactions and their dynamics, and 2) metrics for the quality of proteomics measurements including protein identification, quantification, interactions, and modifications.

The Proteomics core facility provides informatics and user support, maintains key instrumentation, and develops new assays such as single-cell copy-number-variation assays.

Current proteomics projects are:

MSLXR structure for mapping protein complexes

MSLXR structure for mapping protein complexes

Application to identification of protein complexes.  Key challenges associated with studying protein-protein interaction networks by chemical crosslinking, mass spectrometry-based approaches are 1) the identification of low abundance crosslinked peptides amidst a complex mixture of uninformative peptides and the confident assignment of peptide sequences to complex fragmentation spectra of crosslinked peptides.  To address these challenges, we recently designed and synthesized a new, homo-bi-functional, ‘mass spec’ labile crosslinking reagent (MSLXR).

Software and data repository developments.  The proteomics core has continually provided new software solutions for modern day mass spectrometry – “proteomics informatics” (e.g. Center supported Transproteomic Pipeline), data standards and interchanges structure (including vocabulary instructions), and the development and application of an open modification database search strategy for identification of crosslinked proteins and the site of crosslinking.