W.M. Keck Foundation Science and Engineering Grant

Investigators:
Neil Kelleher, Northwestern University
Philip Compton, Northwestern University
Navdeep Chandel, Northwestern University

W.M. Keck Foundation Science and Engineering Grant
Protein complexes are cellular machines that manage and perform most functions in our cells and in all living organisms. Scientists continue to struggle to understand their composition, their structure and how they can malfunction. Because the most revealing and accurate approach—examining native complexes as entire units—has seemed virtually impossible, most analyses have used mass spectrometry of protein fragments, which may lead to partial or misleading results. A team from Northwestern University, in collaboration with Thermo Fisher Scientific, plans to overcome this major barrier in disease research by developing a new kind of mass spectrometer that combines the advantages of Time-of-Flight (TOF) and Fourier Transform (FT) analyzers. This instrument will be used to separate an intact protein complex from a mixture and then detect it directly or activate to release its subunits. The instrument will then detect the intact masses of subunits and the fragmentation products that result from their stepwise disassembly. To this platform, they will couple new separation strategies and software, followed by application of the combined system to mitochondrial complexes isolated from models of aging and kidney cancer. This integrated workflow will constitute a major advance in protein mass spectrometry, accelerate the understanding of disease at a molecular level and address a key challenge of this century: to define the human proteome.

Collaboration Publications

  • Skinner OS, Do Vale LH, Catherman AD, Havugimana PC, de Sousa MV, Compton PD, Kelleher NL "Native GELFrEE: a new separation technique for biomolecular assemblies." Anal Chem, 2015, 87(5) p. 3032-8.
    Summary | Full Text (DOI)

  • Belov ME, Damoc E, Denisov E, Compton PD, Horning S, Makarov AA, Kelleher NL "From protein complexes to subunit backbone fragments: a multi-stage approach to native mass spectrometry." Anal Chem, 2013, 85(23) p. 11163-73.
    Summary | Full Text (DOI)

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