Martin Humphries
LAB

General introduction



Integrins as molecules: the Velcro of our body



Integrins are sticky molecules that are found on the surface of all cells. One of their functions is to hold our body together and they do this by acting as a type of molecular “Velcro” that keeps our organs and tissues from falling apart.

Integrins also act as transmitters and receivers of information between the outside and inside of cells. This enables them to respond appropriately to changes in the cell's environment. In this way, integrins receive signals from the cell's surroundings and in turn transmit the information into the cell. These signals tell the cell, for example, to divide to help repair a wound or to move to a site of infection to fight a disease.

The control of these signals requires very fine tuning. This is regulated by shape changes in the integrin molecules. In simple terms, one shape corresponds to an integrin that is switched off and another shape to an integrin that is switched on. Research is being performed to understand exactly how these shapes changes happen, how they are translated into signals and how the signals tell a cell what to do in response.


Sometimes signalling by integrins goes wrong, which can lead to disease. When integrins malfunction, cells start to move and stick in the wrong place. These mistakes can result in conditions like blocked arteries and heart disease, secondary cancerous tumours and certain autoimmune conditions such as rheumatoid arthritis and inflammatory bowel disease. A detailed understanding of how integrin signalling works can potentially lead to the manufacture of new medicines to treat these life-threatening disorders.


Integrin and syndecan signalling: the compass of the cell



Cells have many different types of sensing molecules located on their surface. Each sensor has a distinct role, be it anchoring the cell in place, letting the cell explore its surroundings or communicating with neighbouring cells. Together, these sensors provide the cell with vast amounts of information about its environment. The cell must then decode, translate and respond to this information.


One example of a cell sensor is syndecan-4. A large part of the arm-like syndecan-4 molecule is on the outside surface of the cell, where it uses its huge, sticky, sugar-coated “hands” to sense and attach to the cell's surroundings.


The environment in which a cell lives is known as the matrix.

Syndecan-4 has a specific role in healing wounds. We know this because mice that lack the syndecan-4 sensor have difficulties making new blood vessels at the site of an injury, and they do not close their wounds as efficiently as normal mice. We have shown that syndecan-4 works in coordination with another sensing molecule on the surface of the cell, the integrin. Together, syndecan-4 and integrin control the ability of a cell to stick to and move across the matrix.

We believe that syndecan-4 may be acting like a compass, directing which way the cell goes. If we delete the syndecan-4 gene so that it is no longer present on the cell surface, the cell no longer has a single front and tail but instead has several at the same time. The cell becomes confused, and it moves around in circles rather than following a straight path. This may explain why mice lacking syndecan-4 have problems closing a wound. Our research aims to discover how the information collected by syndecan-4 is decoded within the cell and how syndecan-4 works in combination with integrins to cause the cell to change its shape, to move and to close a wound.


Integrin proteomics



Information about integrin proteomics will appear here soon.


Fibronectin and other ECM molecules



Information about fibronectin and other ECM molecules will appear here soon.


Anti-integrin antibodies



Information about anti-integrin antibodies will appear here soon.