Mechanisms of Cytoplasmic Streaming

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This project will explain the intricate characteristics of intracellular transport systems by determining the biophysical mechanisms responsible for organelle movements in plant cells through a combination of biological, computational, and statistical approaches. Biological systems are characterized by highly complex traits that result from the interplay of much simpler components. One of the major challenges in modern biology is to define the interactions of these basic components in order to arrive at the properties of the full system. Intracellular transport along cytoskeletal filaments represents such a biological system that is tractable with today's technology. Importantly, this transport plays fundamental functions in establishing cell polarity, in mediating growth, and in responding to the environment or to pathogens. Therefore, better understanding of the mechanisms underlying intracellular movements as provided by this project may impact, for example, agricultural yield or treatment of diseases. This project will also establish a paradigm for the cross-disciplinary training of graduate students at the interface of molecular cell biology, computational biophysics, and statistical machine learning. This training will be extended to undergraduate and high school students who will participate in carefully selected research projects appropriate for their background. Broader dissemination of the research findings will occur via a dedicated website as well as through lectures for the general public.Cytoplasmic streaming in plant cells is characterized by the rapid movement of organelles along the actin cytoskeleton. While it is known that these movements are driven by class XI myosin motor proteins, the precise mechanism for the propulsive mechanism is still debated. One model posits that myosin motors directly associate with individual organelles and pull them actively along actin filaments. Another model proposes that only a few organelles such as the ER directly bind to motors while all other organelles are propelled indirectly by binding to the actively moving organelle(s). A third model predicts that a small number of actively moving organelles generate a hydrodynamic flow in the cytoplasm that transports other organelles passively along this stream. This project will test these motility models by developing a series of rigorous tools to model, measure, and evaluate intracellular dynamics. First, stochastic models will be developed that translate the concepts of the three motility models into explicit biophysical descriptions for computer simulations. Second, novel analytical tools will be developed that are able to capture and describe the complex behavior of organelles in living cells with high spatiotemporal resolution. Third, a machine learning approach based on Bayesian considerations will be designed that can evaluate motility models based on experimental data. Combined with novel tools for experimental interference with specific organelle movements and identification of the cellular cargo of two representative myosin XI motors, this research will deliver a new level of understanding of intracellular transport along the cytoskeleton that will impact cell biological interpretations for all eukaryotic systems.