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Biochemsitry and signaling in disordered and crowded cells : a new space odyssey| old_uid | 8939 |
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| title | Biochemsitry and signaling in disordered and crowded cells : a new space odyssey |
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| start_date | 2010/06/17 |
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| schedule | 13h30 |
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| online | no |
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| summary | Traditionally, the biochemical and signaling pathways within cells have
been viewed by biologists as static objects with no space dependence. More
recent experimental and modeling works in systems biology take into
account their dynamics in time, but spatial aspects are still hardly
investigated. Most often, they rely on mean-field equations ("laws of
mass-action") that are strictly valid only if the reaction medium is
dilute, perfectly-mixed and spatially homogeneous. Many of these
assumptions may be violated in cells. Notably, single-cell measurements
show that protein diffusion in most compartments (including cytosol,
nucleus and membranes) is anomalous. This phenomenon is thought to be
caused, at least in part, by physical obstruction to diffusion due to
large-size obstacles, that actually abounds in cells (organelles, internal
networks, large macromolecular complexes...). Fundamentally, these
experimental observations tell us that cellular media can be considered as
spatially inhomogeneous. To evaluate the effects of this inhomogeneity, we
need to develop spatial cell biochemistry. In this talk, I will show that
individual-based simulations can be used as a tool to understand several
aspects of anomalous diffusion in cells and present examples of the
effects it could have in the case of intracellular enzyme reaction and
protein aggregation. Notably, the latter case is relevant to the study of
aging in the bacterium Escherichia coli. Our simulations indeed suggests
that molecular crowding plays a prominent role in this phenomenon. I will
conclude with a brief presentation of our current effort towards hybrid
simulation methods, i.e. simulation techniques mixing continuous
mean-field modeling at the relevant length scale or spatial location, with
discrete, individual-based simulations in other locations. |
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| responsibles | Dutech |
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