WHAT WE DO
Cell Migration and Metastasis
The human body is composed of billions of cells. During embryonic development inside the mother’s womb, many cells have to move to find their correct position within the body in order to form the structures of the different tissues and organs. After development has finished, there are several cell types in the human body that can move, for example to find and eliminate bacteria or to close a wound. This process is called 'cell migration'.
Cells are small, fluid-filled entities enclosed by a membrane. The flexible membrane is structurally supported by a skeleton, which is made up of 3 types of dynamic polymer - microtubules, intermediate filaments, and actin.
We study Actin, which we already know can change cell shape and initiate migration. It does this by making more of the polymer directly underneath the flexible membrane thereby pushing it outward. However, we still don’t know how this shape change and migration occurs in such a controlled and timely manner during development, wound healing or migration of defence cells. Cell migration is important for the normal functioning of our body but if it 'goes wrong' it can cause disease. One example is cancer metastasis, the spread of a primary tumour to distant organ. It is this metastasis of tumours (taking cancer from stages 1/2 to 3/4) which significantly reduces survival rate.
In our laboratory, we are studying how normal cells migrate in a controlled manner and why cells migrate aberrantly during metastasis.
This movie shows a migrating cancer cell. The cell contains a fluorescently labelled protein which indicates where at the leading edge of the cell, the polymer forms and pushes the membrane forward.
This movie shows a cancer cell during the uptake of receptors by endocytosis. Two proteins that control this have been fluorescently labelled to evaluate their appearance during this process.
In order for the body to function properly the billions of cells that make it up have to communicate with each other. They communicate by sending out signals that can be recognized by “antenna”, which are called “receptors”, on the surface of other cells. When a signal reaches a receptor, the receptor becomes activated, which stimulates cells to react and change their behaviour. As a consequence, a cell may devide or move. The signal is stopped by removal of the activated receptors from the cell surface by uptake into vesicles, small compartments that are surrounded by a membrane. This process is called “endocytosis”.
Endocytosis is important for the normal functioning of our body but if it “goes wrong” it can lead to disease. For example, in the case of cancer, when the process of endocytosis is altered, cells may receive more signals instructing them to divide causing tumour growth or they may receive more signals instructing them to migrate causing tumour metastasis.
We are studying the basic mechanisms of endocytosis of receptors using single cells cultured in the laboratory. We are analyzing how cells normally control the uptake of receptors. We also visualize individual proteins recruited to the vesicles by labeling them with a fluorescent dye allowing us to analyze their recruitment in living cells in real time using a microscope.