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Orexin-A, a peptide that can convince cancer cells to commit suicide Britta Wachter signal transmission via several carrier I’m gonna kill myself! Cancer is a very common disease these days and many researchers are trying to find ways to protect against cancer and to cure it. Just recently researchers found that a small peptide, called orexin-A which can be found in many parts of the body (e.g. gastrointestinal tract, pancreas, kidney, thyroid, lung, testis and placenta) can cause cancer cells to commit suicide. To be able to hopefully apply these effect one day as an effective anti-cancer tool it has to be found out how orexin-A exactly convinces the cells to commit suicide. Cell suicide occurs for example when a cell gets a specific signal from its environment that tells it to kill itself. To perceive signals in general, every cell possesses so called “receptors” on its surface that function according to the “key-lock” principle. The receptors are the locks and extracellular signals are the keys. When such a key finds its appropriate lock and binds to it, it thereby activates a specific signal pathway in the cell. In this pathway several carrier molecules transmit the message “key has bound to lock” to a terminal molecule which then gives the cell further orders what to do next. Because a cell is receiving many different signals at the same time, a huge amount of receptors exist as well as several signalling pathways with different carriers. Orexin-A is one of these key-signals and its lock is called OX1-receptor. In case of cell suicide, researcher found out that the terminal molecule is p38. p38 is an enzyme that can amongst other things induce cell suicide. In this study I tried to figure out what carriers are involved in the transmission of the orexin-A signal that convinces the cell to commit suicide. For this reason, suggested carriers have been genetically altered so they couldn’t work anymore or they have been blocked with pharmacological substances. Then it was tested if the pathway still worked and the signal arrived at the terminal stop or not. If the signal did not arrive at the terminal stop, it can be suggested that, the blocked carrier-molecule is part of the signalling pathway. So far three possible carriers have been identified. Two of them belong to the group of small G-proteins and transmit the signal shortly after it was passed from the receptor to the first carriermolecule. The other identified carrier transmits the signal directly to the terminal stop. Further research has been done to identify the remaining carriers involved in this pathway. Degree project in biology fall 2007 Examensarbete i biologi, 20 p Biology Education Centre and Department of Neuroscience, Uppsala University Supervisor: Dr. Jyrki Kukkonen