July 5, 2005
Successful Young Researchers, Part III: Cell detectives, looking for clues on Leukaemia
By Natascha Plankermann
Searching for clues is not only the work of detectives, it`s also taking place in a laboratory as part of the work that Prof. Markus Müschen and his team of young researchers in the laboratory for molecular stem cell biology at Düsseldorf`s Heinrich-Heine University are carrying out on cells: they are comparing stem cells which normally develop into Lymphocytes (in white blood cells) with damaged cells which develop into Leukaemia, and at the same time have stumbled across gene breaks and pirate proteins.
The underlying question behind many of the experiments carried out by the twelve scientists working with Prof. Müschen is: How does Leukaemia originate? "Stem cells are a model for normal developmental activity to us in which the same dysfunctions are always emerging. The Search System SAGE (Serial Analysis of Gene Expression) help us to find out what the genetic changes of a normal situation are and to recognise the pattern behind it", explains Prof. Müschen. Profiles of cells are created which are already early lymphocyte progenitor cells. Lymphocytes have the task, as white blood cells and therefore part of the body`s immune system, to identify dangers such as bacteria or viruses and to make sure they are destroyed.
Gene breaks can sometimes happen during normal cell development, after which the broken gene pieces come together in a new way. "There are four breaking events, that happen particularly often and lead to certain types of Leukaemia", explains Müschen. One of these disease causing phenomena is the breakage of chromosomes 9 and 22. Afterwards, new, unnatural chromosome formations come into being. "In this case many genes are responsible for the destruction of normal development. "Müschel and his colleagues have just detected a specific, appropriately named 'signal gene': It sends out signals and thus captures a new partner - like a pirate. "In this way cells are tricked to go down a wayward path. They now carry a survivor signal inside which pretends to be autonomous, and the cell grows without control.
This is the general tactic of Leukaemia cells, which reminds Prof. Müschen of societal phenomena: "These cells try to become deaf to the signals of their environment. Normally, they have organs for recognition, receptors for messages from outside - for positive and self-destructive commands alike. "Since these receptors are missing, the blood cancer cells can evade the controls throughout the organism and need only proteins to develop unconsciously malignant. Discovering the inner survival strategy of Leukaemia cells is the first step in shutting them down. Thus the detective work of Prof. Markus Müschen and his team is important for clinics in Paris, Boston and Chicago who are working on applying the results of this research. The main thing in the long run is to cultivate stem cells when they develop good characteristics - and to kill them off if they show unnatural development.
Müschen started his research in 1998 at the Cologne Genetic Institute, where he carried out his scientific training after receiving his licensure. Two years ago the call came from Heinrich-Heine University: the scientist`s research had been chosen for funding by the Stem Cell Network in NRW. Now he leads a group of twelve students working towards their diplomas and doctorates in an independent department, whose work is being supported throughout the NRW region with 1.25 million Euro for a total of 5 years. Müschen also appreciates the regular conferences held by the network and the exchange of colleagues such as Prof. Jürgen Hescheler from the University of Cologne.
Full article available here.
