Phosphotyrosine-dependent regulatory mechanisms of mammalian brain development: A large-scale phosphoproteomic and biochemical study.

University Of Vermont & State Agricultural College, Burlington VT

Investigators

Abstract

This PI seeks to understand how neurons of the developing mammalian brain are appropriately positioned in the brain. During brain development many neurons migrate from their places of birth and are guided by cues in their environment to make the critical connections and structures of a functioning brain. This study will use biochemical, cell biological and newly developed proteomic approaches to study proteins that are known to be essential for neuronal positioning, but whose regulation is poorly understood. A major focus of the study will be the characterization of novel tyrosine phosphorylation events recently identified by Ballif on these neuronal-positioning proteins from mouse brain. Tyrosine phosphorylation is one of the most dynamic mechanisms reversibly regulating proteins and altering cell fate. It is anticipated that this study will make clear the role of targeted tyrosine phosphorylation events on critical proteins governing brain development. Additionally, this study will identify and quantify across development many thousands of tyrosine phosphorylation events on hundreds of brain proteins, accomplishing in a few years what would have required decades using traditional methods. To accelerate the research of other developmental neurobiolists in the field, all identified phosphorylation events will be submitted to public databases including Phosphosite (http://www.phosphosite.org). On the heels of the genomic revolution today's undergraduate and graduate students need access to training in proteomic technology. In collaboration with established infrastructure and outreach programs in Vermont, Dr. Ballif will teach a proteomic module to over 150 undergraduates at nine institutions of higher learning in Vermont; will mentor in research projects two full time graduate students and more than ten undergraduate summer students (including minorities); and will train the proteomics staff in large-scale quantitative proteomics making this technology available to the many investigators it serves each year.