What are the spectrum, frequency and consequences of errors in protein synthesis? How do cells sense and respond to misfolded proteins, particularly in the eukaryotic cytosol? How does stochasticity in protein synthesis alter the composition and stability of the proteome? Are some errors beneficial? Does error-induced protein misfolding influence the progression of neurodegenerative diseases such as ALS?
We are pursuing mechanistic answers to these questions, taking a biochemical and genetic approach, with an emphasis on developing high-resolution, high-mass-accuracy mass spectrometric techniques for proteome-scale quantitation. From a theoretical standpoint, we are interested in understanding the imprints that natural selection on fidelity and misfolding leave on evolving genes and genomes.