Mammalian Gut Microbiome Metaproteomics
People: Carlos Gonzalez, Ellen Casavant

Ninety percent of the cells and 99% of the genes in the human body are not human at all, but microbial. The vast majority of these organisms live in the gastro-intestinal tract where they can reach concentrations of 10^12 cfu/ml. The Elias lab is collaborating with the Sonnenburg Lab (microbiology and Immunology, Stanford) to applying our proteomic techniques to the study of the human gut microbiome. By applying mass-spectrometry based proteomics and developing specialized computational tools to handle large, poorly-defined systems, we provide a new way to observe and quantify the expression of the millions of genes present in the system. Using germ-free mouse models (Sonnenburg Lab), we can make experimental perturbations on defined communities to study issues ranging from diet and obesity to infection and antibiotics. In particular, we are interested in how proteins secreted by the host affect and are affected by the resident microbiota.

MHC I associated protein turnover using quantitative mass spectrometry
People: Niclas Olsson, Shelley Dutt

Protein degradation and immune system surveillance are tightly interconnected. Aside from recycling proteins to recover amino acids for future biosynthesis, protein degradation is essential for reporting pathogenic peptides to the immune system. In a cell, degraded peptides, often of viral origin, are loaded onto MHC I molecules and then presented to the immune system at the cell surface. Self peptides derived from endogenous proteins that activate an immune response, however, can lead to autoimmune diseases, but can also provide a route towards sensitive cancer diagnosis or treatment. Still, little is known about the exact nature of peptide antigen presentation, in health and disease and it is therefore of great interest to investigate MHC I associated presentation and turnover. By using quantitative mass spectrometry and ribosome profiling methods we want to shed light into protein turnover affecting autoimmunity.

Proteome turnover in aging and infectious disease
People: Kavya Swaminathan

We are developing mass spectrometry-based methods to investigate the role of protein turnover in aging. Several investigations have linked aging to general decreases in protein synthesis, impaired molecular chaperone activity, impairment of protein degradation machinery, and accumulation of damaged proteins. Since this failure to maintain proteostasis can have catastrophic consequences, establishing a systems view of the changes that occur in overall protein stability with increasing age will be integral to our understanding of the pathways involved in aging and age-related diseases. Quantitative measurements of protein synthesis and degradation will indicate modes of regulation and may suggest eventual avenues for the therapeutic intervention.