What is cell death program

09.03.2000 09:55

When the cell death program is disrupted ...

Jutta Reising Communication and public relations department
Westfälische Wilhelms-Universität Münster

The junior research group at the Interdisciplinary Center for Clinical Research at the University of Münster deals with the mechanisms of programmed cell death.

Every minute in the human organism numerous of its many trillion cells perish. At the same time, new cells are constantly being formed. These processes already play a central role in embryonic development and later take place in small children as well as in old people. What is important, however, is a balance between cell death and new cell formation. If this balance is disturbed, serious diseases threaten: If too few cells die, for example cancer can develop, if cell death progresses too rapidly, this can explain degenerative brain diseases such as Alzheimer's. Scientists around the world are currently working to better understand the mechanisms that control the cell death program inherent in every organism. At the same time, based on the new results, therapeutic strategies are being developed to "repair" a disrupted cell death program and thus combat numerous diseases more effectively.

At the University of Münster, the lecturer Dr. Jochen Prehn headed the junior research group of the Interdisciplinary Center for Clinical Research (IZKF) with a focus on this topic. With regard to the content of the Münster IZKF, namely research into chronic diseases, studies of programmed cell death, also known as apoptosis, play an important role. This phenomenon could already be described morphologically over 100 years ago. But only since more than 20 genes have been identified that are involved in the cell death program in the last ten years has it been booming in this area. With molecular biological methods one is now on the track of the genes or the mechanisms controlled by them more closely with the aim of being able to intervene in the events later, among other things, by means of gene therapy.

The research carried out mainly on cell cultures by Prehn and his colleagues is currently concentrating on the question of how the cell receives the signal that it should die. As the 36-year-old pharmacist explains, certain protein-splitting enzymes, so-called proteases or caspases, play a key role in the unwinding of the cell death program. Factors that activate this energy are released from the mitochondria, the cells' energy centers. The release of these factors is genetically controlled, but, according to Prehn, can also be triggered by other mechanisms, such as an undersupply of tissue with nutrients. In order to precisely follow the mechanisms in their process and make them visible under the microscope, the young scientist marks gene products with a green fluorescent protein and smuggles them into the cell.

At the same time it is investigated how the activity of the caspases can be influenced. Depending on where the defect is, i.e. whether the cell death program is running too fast or too slowly, the therapeutic point is to stimulate or slow down the process. Corresponding drugs based on this principle are already being developed. Nevertheless, these treatment approaches are currently still in their infancy, as Prehn emphasizes. The focus of his interest is the targeted inhibition of apoptosis in the case of stroke, Alzheimer's and myocardial infarction. Such an inhibition of programmed cell death or the activity of the corresponding enzymes is important in order to prevent cardiac muscle or brain tissue from being destroyed by the temporary interruption of the blood supply. This is particularly important in the brain, as nerve cells do not renew themselves.

Should the new strategies prove to be successful, this could, among other things, provide new insights into the exact mode of action of chemotherapy in cancer. So far it was only known that the drugs used there, the cytostatics, act like cell toxins and destroy the cells accordingly. It can now be proven for the first time that they basically also trigger apoptosis or stimulate the cell death program. Further research will need to clarify why some tumors respond to the drugs and others not or only for a limited period of time.

When carrying out their research work, the five-year junior research group offers the young scientist framework conditions that other researchers can only dream of at the beginning of their scientific careers. "I have ideal conditions here for intensive research. The excellent conditions are easily comparable to a Max Planck Institute," enthuses Prehn, who worked in the field of apoptosis research in Chicago after completing his doctorate in Marburg in 1993/94. Immediately after his habilitation in 1997 in Marburg, he received the attractive position in Münster - an important step in the future scientific career of the then 33-year-old pharmacist. As the head of the group, which currently includes three postdocs, two doctoral students, three MTA and a secretary, he is his own boss, so he does not have a clinic or institute director over himself like other young scientists, but can freely switch and control what also applies to the acquisition of third-party funds.

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Nutrition / health / care, medicine
Research projects