We now have a near complete parts list of all the molecules constituting cells. However, we still only poorly understand how all these tiny molecules self-organize into much larger organelles, cells, and organisms. Our group aims to elucidate principles underlying this organization. Specifically, we study how the proteome partitions between nucleus and cytoplasm. We aim to decipher the underlying molecular mechanisms, and ask how different nuclear composition affects biological function. To address these questions we employ and develop mass-spectrometry based proteomics and combine this technology with computational, biochemical, and imaging approaches. Our main research models are human tissue culture cells and the eggs, cell-free extracts, and embryos of the frog Xenopus laevis.
Outlined below are a few examples of questions and aims we are interested in. For more background, please see the research subsections menu on the left and our publications.
- Developing multiplexed MS methods for quantifying low abundant proteins (~1 nM) such as transcription factors and kinases
- How does nuclear composition change during development? How is this change able to act as a developmental timer that turns on transcription at the midblastula transition?
- How does nucleocytoplasmic partitioning differ between cell types?
- Several inhibitors of nuclear export are showing promise in clinical trials against cancer. Can we measure changes in nuclear localization upon drug addition to understand how they work?
- Can we add prokaryotic proteomes (several thousand proteins that have never seen a nucleus) to eukaryotic systems and measure their nuclear partitioning to determine which physiochemical properties of proteins determine flux across the nuclear membrane?
- Can we systematically measure the binding constants for active transport of proteins into and out of the nucleus via importins and exportins for the entire proteome? Can we integrate these measurements with other data to predict nucleocytoplasmic partitioning?
- Since measuring the native size for thousands of proteins, we have been surprised by how many proteins inside the cell appear to be in complexes. Are most of these complex interactions weak or strong? Can we develop methods to measure the strength of these interactions that could help us better understand the nature of cytoplasm?