Wellcome Trust Centre for Cell-Matrix Research
The Wellcome Trust Centre for Cell-Matrix Research at the University of Manchester pursues advances in the understanding of extracellular matrix (ECM) biology and its contribution to human diseases. The Centre was established in 1995 and Professor Charles Streuli is the Centre's Director.
A key aim for the Centre is to clarify the roles of adhesion molecules, found on the exterior of cells and how they bind to and organise the ECM. These interactions ultimately affect cell behaviour and are of huge importance medically: defects in cell-ECM interactions underpin many diseases, including cancer, diabetes, heart disease, osteoarthritis, inflammatory disorders, some forms of blindness, and many genetically inherited conditions.
Research and discoveries
Studies at the centre include explorations of how cell-ECM interactions control the development and function of the mammary gland. These have shown that one of the central problems in cancer is alteration in cell adhesion: either the receptors change subtly, or the enzymes that they control become altered or mutated, so the cells don’t know how to behave properly. Understanding the behaviour of normal breast cells is likely to suggest new possibilities for the treatment of breast cancer.
Other research explores why fibrous tissue forms after tendon injury and sticks the tendon to the bone, causing pain and stiffness. Recent studies reveal that a thin layer of epithelial cells, usually found in skin, cover the tendon, protecting it from damage. When this layer is damaged, the tendon cells make the unwanted adhesions, which stick the tendon to nearby tissues. Discovery of this completely new layer of tendon cells has changed the way we think about how tendons are made and maintained. Future research aims to find ways of protecting the tendon epithelium to prevent adhesions forming.
Researchers are also tackling a major challenge in stem cell biology: how to direct stem cells to become a specific cell or tissue type. At present, effective strategies to direct embryonic stem cells to form for example, a functional heart or lung are still lacking. Scientists at the Centre have developed a new protocol that allows human embryonic stem cells to be programmed to form cartilage cells. This is an important step toward growing functional cartilage and has enormous potential for treating arthritis and cartilage reconstruction in sports medicine. It also suggests a protocol for making other medically important cell or organ types, which could advance the field of regenerative medicine overall.
Researchers at the Centre include:
Dr Keith Brennan looks at the regulatory pathways that control the development of mammalian embryos. As many as two hundred different cell types are produced during this development, but very few, perhaps only seven or eight, signal transduction pathways control these processes. Dr Brennan’s group are investigating how these pathways regulate cell behaviour such as adhesion, survival, migration and proliferation.
Dr Mike Briggs is a Wellcome Trust Senior Research Fellow who investigates the proteins secreted by chondrocytes – cells that make up cartilage. These proteins are incorporated into the ECM. The calcification of the ECM in cartilage in bones is an important step in bone creation. Chondrocytes exporting incorrect forms of these proteins can directly affect the development of bone, causing conditions such as short-limbed dwarfism.
Dr Patrick Caswell is a Wellcome Trust Research Career Development Fellow, studying integrins and signalling receptors – proteins found on a cell’s surface that enable them to interpret their physical and chemical environment. These help dictate whether a cell grows, moves, specialises or dies. Integrin proteins are found both on the cell surface and inside the cell stored in specialised compartments known as endosomes. Dr Caswell’s group look at how movement of integrins between the two locations control the signalling pathways within the cell, which determines how the cell will respond to its environment. This is important in the understanding of cancer cells that manipulate integrin trafficking to metastasise.
Dr Rachel Lennon is a Wellcome Trust Intermediate Clinical Fellow identifying the underlying mechanisms of kidney disease. Normally our kidneys are responsible for removing waste products from blood and keeping protein molecules in circulation. The presence of excess protein in urine, known as proteinuria is often an early sign of kidney disease. Dr Lennon is using mass spectrometry and proteomics to look at the interactions between cells, their signalling pathways and the ECM. By examining these interactions it is hoped that new insights and treatments into kidney disease will be found.
- Wellcome Trust
- Wellcome Trust Centre for Neuroimaging
- Wellcome Trust Centre for Stem Cell Research
- Wellcome Trust Centre for Gene Regulation and Expression