CSB2: Council for Systems Biology in Boston
CCC2010 poster prize winners announced
Published February 2, 2010
CSB2 is happy to announce that Melanie Müller from the Harvard Physics Department and Kenneth Evan Thompson from the MIT Biology Department won the two poster prizes at CCC2010. Each recipient will receive a $200 award, funded by the Center for Modular Biology under NIH grant NIGMS68763. The abstracts of their poster presentations follow:
#19 Intracellular cargo transport: Molecular motors playing tug and tug-of-war
Melanie J.I. Müller1,2, Florian Berger2, Stefan Klumpp2, Reinhard Lipowsky2
1Department of Physics, Harvard University, 2Max Planck Institute for Colloids and Interfaces
Intracellular transport is based on molecular motors that pull cargos along cytoskeletal filaments. Kinesin and dynein motors walk along microtubule filaments, while myosin motors move along actin filaments. One motor species walks actively only into one direction along the filament, e.g. kinesin-1 moves to the microtubule plus-end, whereas cytoplasmic dynein moves to the microtubule minus-end. However, many cellular cargos are observed to move bidirectionally, involving both plus- and minus-end-directed motors. The presumably simplest mechanism for such bidirectional transport is provided by a tug-of-war between the two motor species. We have studied this mechanism theoretically, using the load-dependent transport properties of individual motors as measured in single-molecule experiments. In contrast to previous expectations, such a tug-of-war is found to be highly cooperative and can lead to fast bidirectional motion with or without pauses, as observed in vivo. Our model reproduces experimental results on bidirectional transport of lipid droplets in Drosophila embryos, which have previously been thought to be incompatible with a tug-of-war scenario. One motor species walks actively only along one type of filament. However, the motor myosin-5, which walks actively along actin filaments, can passively diffuse along microtubules. Cargos that are transported along a microtubule by one kinesin and one myosin motor exhibit interspersed moving and diffusing events and increased processivity. We explain this behavior by a stochastic tug model similar to the tug-of-war model.
#23 Heterospecific modules for molecular engineering identified from a synthetic coiled-coil interactome
Kenneth Evan Thompson, Aaron Reinke, Robert Grant, Amy Keating
Department of Biology, MIT
Coiled-coil dimers, in which two alpha helices intertwine to form a supercoiled bundle, are widely used to mediate interactions both in biology and materials science. Although coiled-coil reagents for inducing homo-oligomerization or hetero-oligomerization of single complexes are commonly employed, the modern coiled-coil toolkit provides limited access to more complex interaction patterns. We have expanded the possible uses of coiled coils in molecular engineering by measuring the complete pair-wise interactions of 48 synthetic coiled coils and 7 human bZIP coiled coils using protein microarrays. Focusing on those peptides that do not strongly self-associate, we have identified a 26-member protein set that includes 27 interacting peptide pairs. The interaction connectivity of these 27 pairs can be used to assemble networks of 3 to 6 proteins with a variety of interactions. Of special interest are peptide pairs that participate in mutually orthogonal interactions. These pairs provide the ability to dimerize separate molecular systems with minimal crosstalk. The interaction geometry of two of these pairs has been confirmed with both solution and crystallographic studies, and we are currently validating the in vivo behavior of the peptides in E. coli and S. cerevisiae. The variety of network motifs discovered in our screen provide new capabilities for synthetic biology and other applications. These protein reagents will be characterized in more detail and made available to the scientific community through open-source biological repositories.