Co - Mentor
The A, B, and C’s of the Tubulin Code: Proteomic analysis of tubulin PTMs and their readers
Microtubules (MTs) are a ubiquitous cytoskeletal element of eukaryotic cells that are critical for nearly every aspect of cellular function, from defining cell shape to driving cell migration, division and signaling. During cell division, for example, MTs are the building blocks of the mitotic spindle, an apparatus that segregates a replicated set of chromosomes between two daughter cells. All MTs self-assemble from a common ab-tubulin building block, but cells can generate functionally distinct MTs in several ways. First, eukaryotic cells express many tubulin isotypes; humans express nine a- and ten b-tubulin isotypes. Second, MT function is modulated by a poorly understood set of post-translational modifications (PTMs). Analogous to the “Histone Code” that regulates chromatin biology, the Tubulin Code hypothesis states that tubulin diversity, which includes isotypes and PTMs, constitutes a code used by the cell to encrypt spatial, temporal, and functional information that specifies MT biology. The Ohi and Sept research groups are using mass spectrometry to comprehensively identify tubulin PTMs that are expressed in cultured cells at defined points in the cell cycle, for example, during mitosis and interphase. Computational approaches combined with mutational studies and live cell imaging are being used to prioritize high stoichiometry PTMs. Through further systems modeling and analysis, we will also gain a comprehensive understanding of the interdependence and regulation of cytoskeletal PTMs. Lastly, a pipeline has been developed to identify proteins that “read” the PTM state of MTs. We will use this strategy to discover proteins that interpret the tubulin code to enable critical physiological processes within the cell.