The Extracellular Matrix
"All things in nature have a shape, that is to say, a form, an outward semblance, that tells us what they are, that distinguishes them from ourselves and from each other. Unfailingly in nature these shapes express the inner life, the native quality, of the animal, tree, bird, fish, that they present to us; they are so characteristic, so recognizable, that we say, simply, it is 'natural' it should be so." Louis Sullivan (1896) Louis Sullivan was an architect from the Prarie school of architecture and is widely considered to be one of the forefathers of the modern skyscraper. Taking leads from nature, his work typically incorporated organic details that were integral to the building itself, a classic example being the Guaranty building. His ideas were taken up by his student - Frank Lloyd Wright - who coined the term "Form is function". One of the more famous examples of FLW's work is Fallingwater, a private residence which encompasses designs that are aesthetic yet functional. In nature, we observe a multitude of examples of this 'form is function' sentiment.
From the problem of protein folding to the development of embryos, basic mechanisms underlying the generation of form (morphogenesis) still remain unresolved. Furthermore, for many biological processes the role played by organisational / architectural properties are yet to be elucidated. In our lab we are developing new tools and databases aimed at understanding the generation and influence of biological structures. One of our main interests is the study of cellular and extra-cellular networks of structural proteins including elastin. Despite decades of study, the role of network connectivity and organisation in the biomechanical properties of structural protein networks still remain poorly understood. Furthermore, while we have witnessed the growth in databases concerned with metabolic proteins, kinases or other signalling elements, very little attention has been devoted to structural proteins. In collaboration with Dr Fred Keeley and Dr Regis Pomes, we are currently studying the role of elastin sequence on its ability to perform its physiological functions.
Other activities:
Elastin
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Evolution of the ECM
Interactions among genes and the proteins they encode form complex networks of associations responsible for the processes of life. There is increasing evidence that disruption of these relationships leads to serious consequences in the form of disease. The extracellular matrix (ECM) represents a group of proteins responsible for interactions external to cells. As such, they play a key role in shaping and maintaining the body plan of multicellular organisms during development and wound repair. Together they form connective tissues, ligaments, tendons, blood vessels, bones and contribute resilience and elasticity to skin, bladder and lungs. Disruptions in this system are thought to contribute to cancer, heart disease, asthma, fibrotic diseases and arthritis. We developed a general approach to defining the components of a biological system by leveraging information deposited in public data sets and applied this approach to construct and analyze a human network of extracellular matrix and related proteins. The proteins are organized in modules representing distinct biological functions and many of these modules can be linked to diseases. Also we compare human proteins to their equivalents in other species to infer important evolutionary patterns. So far, this analysis has highlighted the limitations of our knowledge of the ECM and identified areas for more focused studies to better understand the structure, function and evolution of the ECM as well as its role in health and disease. This is important because understanding how the matrix is organized in humans and other organisms can provide insight into disease mechanisms and allow the prediction of new disease associations.
