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.
Aim 3 : Determine the morphogenetic effect of the mechanics internal to a branching epithelium.
Aim 4 : Determine the morphogenetic effect of the mechanics external to a branching epithelium. Part of this project will be a determination of the appropriate constitutive laws, as well as quantification of the physical parameters, of the tissues involved in branching epithelia. This can only be effectively done by theory-guided experiments in conjunction with experiment-guided theory. The synergy of mechanistic mathematical modeling, sophisticated simulation, and experiment designed and analyzed in a quantitative mechanical framework will - help support or refute hypothesized mechanisms - clarify the relative roles of various physical phenomena in creating branched systems of ducts - help drive a part of biomedicine towards the future as a more exactly quantitative discipline.

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 #
3R01GM096195-01S1
Application #
8135945
Study Section
Special Emphasis Panel (ZGM1-CBCB-5 (BM))
Program Officer
Haynes, Susan R
Project Start
2010-08-01
Project End
2014-06-30
Budget Start
2010-08-01
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$48,861
Indirect Cost
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
Bower, Danielle V; Lansdale, Nick; Navarro, Sonia et al. (2017) SERCA directs cell migration and branching across species and germ layers. Biol Open 6:1458-1471
Li, Zhilin; Ji, Haifeng; Chen, Xiaohong (2017) ACCURATE SOLUTION AND GRADIENT COMPUTATION FOR ELLIPTIC INTERFACE PROBLEMS WITH VARIABLE COEFFICIENTS. SIAM J Numer Anal 55:570-597
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
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
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
Wang, Zhaohui; Li, Zhilin; Lubkin, Sharon (2014) A Robin-Robin Domain Decomposition Method for a Stokes-Darcy Structure Interaction with a Locally Modified Mesh. Numer Math 7:435-446
Xiao, Li; Cai, Qin; Li, Zhilin et al. (2014) A Multi-Scale Method for Dynamics Simulation in Continuum Solvent Models I: Finite-Difference Algorithm for Navier-Stokes Equation. Chem Phys Lett 616-617:67-74
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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