University of Minnesota
Department of Biomedical Engineering
http://www1.umn.edu/bme
612-624-4507

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David Odde

David Odde

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Cell Growth and Division

Mitosis

The proper segregation of chromosomes is achieved by a sorting machine known as the mitotic spindle. The spindle is composed of dynamic, self-assembling microtubules and molecular motors. We are studying the dynamic interplay of these nanomachines as they sort out the chromosomes, so that each of two nascent daughter cells gets a complete genome. Our approach is to integrate computer modeling with live fluorescence microscopy, cryo-electron microscopy, and genetics. In our models we also simulate the imaging process, an approach we call "model-convolution", which facilitates hypothesis testing. Understanding the mechanochemical basis of mitosis will give us more rational approaches to interfere with mitosis, for example in cancer therapy and control of restenosis after stenting.

Cell Growth

Each cell type has a characteristic size, ranging from a few cubic micrometers for bacteria to 1000 cubic micrometers for mammalian tissue cells. A key question is what controls cell size. We are studying how mechanical force stimulates cell growth using neurons as our model system. Interestingly, neurons can be induced to form axons de novo in response to appropriate levels of mechanical tension. In addition, we are investigating how neurons respond to the mechanical stiffness of their environment. These studies will give us a better understanding of how to promote nerve regeneration in vivo and engineer neural tissue in vitro. In addition, they will provide us with new insight on the mechanochemical basis of environmental stiffness sensing, which controls stem cell differentiation, and of cell polarization, which is required for axon growth.

Microtubule Dynamics

The positioning of intracellular structures is determined largely by the organization of the cytoskeleton, a collection of self-assembled protein filaments inside eukaryotic cells that serve as nanometer-scale railroad tracks for molecular motors and their associated cargoes. A prime example is the movement of DNA during mitosis. When cells divide, replicated chromosomes attach specifically to the ends of cytoskeletal filaments called microtubules. Microtubules then undergo stochastic switching between rounds of assembly and disassembly, which ultimately serves to mediate the movement of one chromosome to one pole and the replicated sister chromosome to the other pole. My laboratory is interested in modelling the kinetics and thermodynamics of microtubule assembly and disassembly, the dynamics of microtubule-associated proteins, and the interplay between mechanical forces and chemical kinetics and thermodynamics. In doing so we hope to better understand and control such seemingly diverse processes as cell division and nerve regeneration, both of which require the reorganization of microtubules.

Selected Publications

Odde D. Getting cells and tissues into shape. Cell. 2011;144:325-326.

Mogilner A, Odde DJ. Modeling Cells in 3D. Trends in Cell Biology. 2011;in press.

Griffin EE, Odde DJ, Seydoux G. Regulation of the MEX-5 Gradient by a Spatially Segregated Kinase/Phosphatase Cycle. Cell. 2011;146:955-968.

Gardner MK, Charlebois BD, Janosi IM, Howard J, Hunt AJ, Odde DJ. Rapid microtubule self-assembly kinetics. Cell. 2011;146:582-592.

Demchouk AO, Gardner MK, Odde DJ. Microtubule Tip Tracking and Tip Structures at the Nanometer Scale Using Digital Fluorescence Microscopy. Cellular and Molecular Bioengineering. 2011;4:192-204.

Castle BT, Howard SA, Odde DJ. Assessment of Transport Mechanisms Underlying the Bicoid Morphogen Gradient. Cellular and Molecular Bioengineering. 2011;4:116-121.

Bicek AD, Tuzel E, Demtchouk A, Uppalapati M, Hancock WO, Kroll DM, Odde DJ. Anterograde microtubule transport drives microtubule bending in LLC-PK1 epithelial cells. Molecular Biology of the Cell. 2009;20:2943-2953.

Lipkow K, Odde DJ. Model for Protein Concentration Gradients in the Cytoplasm. Cellular and Molecular Bioengineering. 2008;1:84-92.

Gardner MK, Odde DJ. Dam1 complexes go it alone on disassembling microtubules. Nature Cell Biology. 2008;10:379-381.

Gardner MK, Hunt AJ, Goodson HV, Odde DJ. Microtubule assembly dynamics: new insights at the nanoscale. Current Opinion in Cell Biology. 2008;20:64-70.

Gardner MK, Bouck DC, Paliulis LV, Meehl JB, O'Toole ET, Haase J, Soubry A, Joglekar AP, Winey M, Salmon ED, Bloom K, Odde DJ. Chromosome congression by Kinesin-5 motor-mediated disassembly of longer kinetochore microtubules. Cell. 2008;135:894-906.

Chan CE, Odde DJ. Traction dynamics of filopodia on compliant substrates. Science. 2008;322:1687-1691.

Schek HT, 3rd, Gardner MK, Cheng J, Odde DJ, Hunt AJ. Microtubule assembly dynamics at the nanoscale. Current Biology. 2007;17:1445-1455.

Nahmias Y, Odde DJ. Micropatterning of living cells by laser-guided direct writing: application to fabrication of hepatic–endothelial sinusoid-like structures. Nature Protocols. 2007;1:2288-2296.

Nahmias Y, Schwartz RE, Hu WS, Verfaillie CM, Odde DJ. Endothelium-Mediated Hepatocyte Recruitment in the Establishment of Liver-like Tissue In Vitro. Tissue Engineering. 2006;12:1627-1638.

Meyers J, Craig J, Odde DJ. Potential for control of signaling pathways via cell size and shape. Current Biology. 2006;16:1685-1693.

VanBuren V, Cassimeris LU, Odde DJ. A mechanochemical model of microtubule structure and kinetics. Biophysical Journal. 2005;89:2911-2926.

Nahmias YK, Schwartz R, Verfaillie CM, Odde DJ. Laser-guided direct writing for three-dimensional tissue engineering. Biotechnology and Bioengineering. 2005;92:129-136.

Gardner MK, Pearson CG, Sprague BL, Zarzar TR, Bloom K, Salmon ED, Odde DJ. Tension-dependent Regulation of Microtubule Dynamics at Kinetochores Can Explain Metaphase Congression in Yeast. Molecular Biology of the Cell. 2005;16:3764-3775.