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In protein-cascades several proteins are connected in series and transmit the signal from one to the other like in a relay race until it reaches its destination for example in the nucleus. But first the signal is outside of the cell. It might be a small molecule, a hormone or growth-factor. This molecule is recognized by a receptor on the cell-surface and bound by it. This binding changes the structure of the receptor, which is extended through the cell-membrane into the inside of the cell. This structural change transmits the outside signal to the inside of the cell. There other proteins recognize the structural change of the receptor and become enabled to bind to it. This binding in turn triggers a change, which is recognized by the following protein and so on until the signal reaches the nucleus. Of course this is a very simplified model. So linear as it is shown here it is not found in nature. And there is also not only one such cascade existing, there are many of them with different but also overlapping functions and to make it more complex with a lot of crosstalk between the cascades.
My research is to discover how such cascades are build. Why are we interested in this topic? Well, at first because we are curious, because it is fascinating to understand how nature functions. But we are also interested, because these signalling-cascades are regulating cell-proliferation and an understanding of these events might enable us to intervene specifically to stop uncontrolled dividing tumor-cells from proliferation. That would lead to cancer-treatment on a molecular and genetic level. Of course we have to know exactly what we are doing so that we do not cause unexpected and unwanted side-effects.
One example for a signalling-cascade which is deregulated in tumor-cells is the so called Raf-cascade. I worked on this cascade during the last years. In principle there are 4 members below the receptor. These are: Ras - Raf - MEK and Erk. Following activation of the receptor, for example by binding of a growth-factor, the receptor binds Ras. This interaction activates Ras which enables Raf to bind to Ras. Activated Raf binds and activates MEK, which in turn activates Erk. Erk finally translocates to the nucleaus and stimulates the cell to divide by gene-regulation. Deregulation may for example be caused by altering Ras to a constantly active form. This constitutively active Ras would continously signal that the cell has to divide and the cell will do so. Indeed we find such a constitutively activated Ras in many tumor-cells. As on the level of Ras there might occur other mistakes on other levels of the signalling-cascade.
It is important in signalling-cascades that different proteins contact each other very closely, that they bind to each other. I mentioned already above that these signalling-cascades are not linear, but that there can be cross-talk. In addition we do not know all members of these cascades and we do not know about the crosstalk of all of them. This is the topic I am working on. I try to discover, which proteins are able to bind to each other. During the last years I worked on Raf and since I am here in Great Britain, I mainly work on MEKK, a member of a parallel cascade. I am using a special test-system for my experiments, the Two-Hybrid System.

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