Objectives: The living world is embedded in the physical world. Small organisms live in a world of diffusion. The rest of us require a system of ducts for transport of all the materials we need to live. Systems of branched ducts are found in lung, kidney, mammary gland, and many other organs. This project's primary objective is to understand the mechanisms of tissue dynamics that create branched systems. It also aims to clarify the best ways to work with continuum mechanical models of morphogenesis to realistically describe mechanics and transport in developing tissues. Additionally, the project will develop new numerical methods for mixture models with interfaces. We will then test these models in a real time living branching system, the early embryonic lung.
Aim 1 : Develop accurate, stable, efficient methods for solving mixture problems with sharp interfaces.
Aim 2 : Develop a suite of models of the mechanical aspects of branching epithelia.

Public Health Relevance

Branching morphogenesis is essential for the construction/reconstruction of our bodies. The insights gained from this collaboration will inform our understanding of normal and abnormal development of the lung and other organs. Many of the methods developed will be adaptable to other problems in the dynamics of cells and tissues, in development, cancer, wound healing, angiogenesis, and other areas.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM096195-03
Application #
8284300
Study Section
Special Emphasis Panel (ZGM1-CBCB-5 (BM))
Program Officer
Hoodbhoy, Tanya
Project Start
2010-08-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$326,684
Indirect Cost
$50,739
Name
North Carolina State University Raleigh
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Bokka, Kishore K; Jesudason, Edwin C; Warburton, David et al. (2016) Quantifying cellular and subcellular stretches in embryonic lung epithelia under peristalsis: where to look for mechanosensing. Interface Focus 6:20160031
Li, Zhilin; Wang, Li; Aspinwall, Eric et al. (2015) Some new analysis results for a class of interface problems. Math Methods Appl Sci 38:4530-4539
Bokka, Kishore K; Jesudason, Edwin C; Lozoya, Oswaldo A et al. (2015) Morphogenetic Implications of Peristalsis-Driven Fluid Flow in the Embryonic Lung. PLoS One 10:e0132015
Bokka, Kishore K; Jesudason, Edwin C; Warburton, David et al. (2015) Morphogenetic implications of peristaltic fluid-tissue dynamics in the embryonic lung. J Theor Biol 382:378-85
George, Uduak Z; Bokka, Kishore K; Warburton, David et al. (2015) Quantifying stretch and secretion in the embryonic lung: Implications for morphogenesis. Mech Dev 138 Pt 3:356-63
Warburton, David; Shi, Wei; Xu, Bing (2013) TGF-β-Smad3 signaling in emphysema and pulmonary fibrosis: an epigenetic aberration of normal development? Am J Physiol Lung Cell Mol Physiol 304:L83-5
Song, Peng; Xue, Jianping; Li, Zhilin (2013) Simulation of longitudinal exposure data with variance-covariance structures based on mixed models. Risk Anal 33:469-79
Al Alam, Denise; Warburton, David (2013) Wingless: developmentally important genes that respond adversely to smoking. Thorax 68:703-4
Liu, Xingping; Wang, Changhao; Wang, Jun et al. (2013) Exploring a charge-central strategy in the solution of Poisson's equation for biomolecular applications. Phys Chem Chem Phys 15:129-41
Li, Zhilin; Song, Peng (2013) Adaptive mesh refinement techniques for the immersed interface method applied to flow problems. Comput Struct 122:249-258

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