During the last stage of cell division, cytokinesis, cells undergo a dramatic change in morphology as they rearrange themselves so as to produce two identical daughter cells. A detailed understanding of how these processes are regulated requires a fundamental knowledge of how different cytoskeletal proteins are spatially and temporally regulated, and how the resultant heterogeneity affects the mechanical properties of the cell. The complexity of these processes makes it nearly impossible to understand without a modeling framework that allows in silico testing of ideas and conceptual models. To elucidate the mechanisms by which cells regulate cytokinesis we need to appreciate how regulation of biochemical signaling cues effect changes in cell morphology. We will develop a suitable computational framework for studying the way in which biochemical regulation of cytoskeletal proteins results in desired cellular deformations during cytokinesis. Our simulations will be used to integrate computational modeling with quantitative measurements of the temporal and spatial changes of different proteins and the associated changes in cell shape during cytokinesis. Specifically, we propose: 1. to develop a computational framework for simulating whole cell, cell shape changes during mitosis;2. to develop an agent-based model of the actin cytoskeleton using a discrete-network representation of interacting filaments, and to use this model to investigate cell morphological changes during cytokinesis.

Public Health Relevance

Successful cell division has long been appreciated as critical to human health. Many cancer- associated genes lead to mitotic and/or cytokinetic failure. In this research we combine computational and experimental tools to study the way that cells regulate their mechanical properties to ensure that each mother cells successfully divides into two equally-sized daughter cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM086704-03
Application #
8217091
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Lyster, Peter
Project Start
2010-04-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
3
Fiscal Year
2012
Total Cost
$308,069
Indirect Cost
$115,019
Name
Johns Hopkins University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Huang, Chuan-Hsiang; Tang, Ming; Shi, Changji et al. (2013) An excitable signal integrator couples to an idling cytoskeletal oscillator to drive cell migration. Nat Cell Biol 15:1307-16
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