Among the defining properties of the eukaryotic cell is its organization into spatial compartments known as organelles. Organelles provide the cell with specialized biochemical environments crucial for processes fundamental to life, from gene transcription in the nucleus to energy production in mitochondria. Coordinating organelle copy number, size, and composition with developmental and environmental cues is one of the chief ways the cell can match its biochemical capabilities with its physiological demands. How does the cell orchestrate flows of matter and energy to produce exquisitely defined organelles at the nanometer and femtoliter scales of a cell? Here I will present recent progress toward answering this fundamental question in cellular biophysics. First, using a stochastic model of organelle copy number control, I will show that cell-to-cell fluctuations in budding yeast organelle copy numbers can be used to rapidly infer the mechanisms by which organelle copy numbers are regulated. I will show how our fluctuation-based inferences suggest resolutions to controversies surrounding the biogenesis of peroxisomes and lipid droplets, organelles responsible for major steps in lipid metabolism. Second, I will describe my recent efforts in understanding the biophysics of protein targeting to organelle membranes. Using single molecule imaging, mass spectrometry-based protein identification, and a mathematical model combining chemical kinetics with transport theory, I will show that spatially localized protein synthesis is key to protein trafficking specificity to the mitochondrial outer membrane, shedding light on a long-standing puzzle in cell biology. I will close by discussing how I plan to use these findings as a springboard to uncover the broad biophysical decision-making principles by which the cell controls organelle biogenesis and how to harness these principles to rationally engineer cellular organelle composition with tools from synthet ic biology for applications in health and energy.
Coffee: 3:30 pm, 245 Compton