Brar Lab Research
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We study the gene regulation underlying meiotic cellular remodeling.
The mechanisms that link cellular differentiation programs and dynamic gene regulation in complex eukaryotic systems remain mysterious. Such programs drive diverse and central biological processes including organismal development, immune function, disease progression, and meiosis. Our lab is focused on the molecular basis for the cellular remodeling accompanying meiosis, the highly conserved process by which gametes are produced.
We study meiosis because it is itself a biologically interesting and important process, but also because it serves as a tractable model for the complex cellular changes that accompany many types of differentiation. We are interested in understanding the fundamental mechanisms by which a cell achieves such changes. Towards this end, we use high-throughput and classical genetic and molecular approaches in budding yeast (S. cerevisiae) to study the role of pervasive short protein synthesis in meiosis, the role of several prominent and diverse stress response pathways in driving cells through the meiotic program, the contribution of regulated transcript toggling to gene regulation, and the modes of translational control that are important in meiotic cells.
Foundational work for Brar lab
In my post-doctoral studies, I globally probed the regulation of the comprehensive cellular restructuring underlying meiosis. Ribosome profiling, the deep sequencing of ribosome protected mRNA fragments, is a new method that monitors protein synthesis with scale, speed, and accuracy rivaling approaches for mRNA measurement (Ingolia et al., Science 2009). I applied this method to numerous time points through the yeast meiotic program in parallel with mRNA-seq and molecular staging to generate a rich atlas of meiotic events and gene expression and the first high-resolution map of protein synthesis through a developmental program (Brar et al., Science, 2012).
This study revealed an unprecedented view of the molecular events underlying diverse aspects of meiotic biology and uncovered numerous new and dramatic instances of dynamic translational regulation through meiosis. The effort also yielded several fundamental surprises with broad significance. Projects in the Brar lab are based on exploring the basis and molecular significance of these discoveries.
Ongoing projects in the Brar lab
Discoveries from this study have motivated several research directions in our lab, focused on answering fundamental questions about gene regulation through meiosis.
Questions that interest us are:
4. What canonical and noncanonical and translational regulation drive meiotis? What is the impact of protein degradation?
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