Quantifying 3D cellular organisation to uncover the structure-function relationships in multicellular tissues

Jackson, Matthew David Bruce (2019). Quantifying 3D cellular organisation to uncover the structure-function relationships in multicellular tissues. University of Birmingham. Ph.D.

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Abstract

A wide range of multicellular forms are observed throughout biology, constructed using tightly regulated developmental processes. Cell communication occurs across these cellular architectures, and loss of normal cell organisation is often deleterious to an organism, suggesting that these cellular structures themselves perform a functional role. Despite this, organisational features of multicellular tissues that support these functions are poorly understood, due to low availability of appropriate datasets, and the lack of a quantitative framework to explore them.
To quantify cell patterning in 3D tissues, organ-wide cellular interactions are converted into a network, and network science algorithms are employed to uncover both local and organ-wide organisational principles of cells in 3D space. Models were used to understand how cellular architecture affects the potential flow of information throughout an organ. Topological analysis of cells in the embryonic plant stem revealed a previously unknown molecular transport conduit, while quantification of cellular organisation in the plant shoot apical meristem revealed mechanisms for the maintenance of the stem cell population.
This work enables the discrete comparison of diverse 3D multicellular tissues, and the identification of structure-function relationships in organs. Understanding the organ-wide design principles that have emerged through evolution will provide guidance for future organ design.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):