Martin Humphries
LAB

General introduction



Integrins as molecules: the Velcro of our body

Written by Janet Askari



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.


Want to learn more?

Read in detail about integrins as molecules.






Integrin and syndecan signalling: the compass of the cell

Written by Hellyeh Hamidi and Mark Morgan



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 extracellular 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 extracellular 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.


Want to learn more?

Read in detail about integrin and syndecan signalling.






Integrin proteomics: building a map of adhesion molecules

Written by Adam Byron



Cells must stick to each other in the right place at the right time. This helps the body to develop and function healthily. Integrin molecules on the surface of cells are critical for normal cell adhesion. But integrins cannot do all this work alone.


Many other molecules in the cell help integrins to function properly. Some of these helper molecules decode communication signals from neighbouring cells; some let the cell respond to these signals; some provide transport within the cell, shuttling molecules that cannot get to integrins on their own.



These helper molecules all team up close to integrins in a cluster of proteins known as a protein complex. Integrin protein complexes are often called “focal adhesions” because they are focal points of cell adhesion. The collection of molecules in a protein complex is actually very … complex (excuse the pun). We still do not know what all the helper molecules are, where they cluster with integrins or when their help is needed. If we knew all this information, we would have a better understanding of how integrin signalling worked. This knowledge could lead to treatments for diseases that occur when integrins or integrin helper molecules malfunction.


Currently, it's a bit like trying to read a map with lots of places missing. We know roughly where things are, but there could be many unknown places, and we don't know all the roads that link the places together. Think of the places on the map as proteins in a cell and the roads as signals or interactions between the proteins. Usually, scientists start at their favourite place (protein) on the map and discover new places and roads that are nearby. Our research has developed a way to look at the whole integrin map at the same time.


Studying all of the proteins in a system is an approach known as proteomics. Our proteomics work has shown that there are hundreds of helper molecules that collect close to integrins in protein complexes. We were surprised to find that the complicated integrin map changed when the cell was in a different environment. This may help explain how communication signals from different tissues of the body make sure cells stick to each other in the right place at the right time.


How do scientists perform proteomics?

We use a technique called mass spectrometry. Find out more about mass spectrometry.


Want to learn more?

Read in detail about integrin proteomics.