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m4 Award for cell death researchers

This year’s m4 Award was presented on 11 October in Martinsried. Among the winners are Dr. Bettina Proneth, Dr. Marcus Conrad, and Dr. José Pedro Friedmann Angeli from the Institute of Developmental Genetics (IDG) at the Helmholtz Zentrum München. As part of a project entitled “METoxicate”, they are searching for novel triggers of a new cell death mechanism known as ferroptosis. Over the next two years, the project will receive a total of 500,000 euros in funding.

Prof. Dr. Horst Domdey (Bio M), Dr. Bettina Proneth (HMGU), Dr. Marcus Conrad (HMGU), Dr. Bernhard Schwab (Bavarian Ministry of Economics). Source: BioM

The m4 Award is presented by the Bavarian Ministry of Economic Affairs in recognition of innovative biomedical research projects that have the potential to lead to business start-ups and are still in the so-called “pre-seed phase”, i.e. the initial stage of a new business or venture. One such project is METoxicate, the main idea of which is to harness a specific form of cell death in order to develop new cancer therapies.

The term ferroptosis was coined in 2012. It is derived from the Greek word ptosis, meaning “a fall”, and ferrum, the Latin word for iron, and describes a form of regulated cell death in which iron plays an important role. “The individual mechanisms involved in this type of cell death only emerge slowly, and our team has already made some groundbreaking work that that is already contributing towards a better understanding of ferroptosis,” says Marcus Conrad, who heads the working group at the IDG.

Ferroptotic cell death in cancer cells

While the term “cell death” does not exactly conjure up positive, health-giving images, the selective destruction of rogue cells– particularly in cancer research – is crucial for the human body. The team of scientists headed by Marcus Conrad succeeded, for example, in proving that cells that cannot produce the ACSL4 molecule are extremely resistant to ferroptosis. Conversely, “cells that express this enzyme respond very sensitively when ferroptosis is triggered”, explains José Pedro Friedmann Angeli, who is also involved in the METoxicate project.

In addition, the latest studies have shown that a whole range of different cancers such as triple negative breast cancer are very susceptible to ferroptosis. “For the first time, this will enable the development of in vivo ferroptosis activators that could be used for the targeted treatment of tumor entities, which are otherwise very difficult to treat,” explains Bettina Proneth, a scientist at the IDG. Buoyed by the financial support of the m4 Award, the METoxicate team would like to focus more closely on long-term therapies for solid tumors, which are difficult to treat.


Further information

* Patients with triple negative breast cancer account for about 15 percent of all breast cancers. The main characteristics of this type of tumor are the lack of both estrogen and progesterone as well as HER2 receptors. The cells in these tumors only have a weak response to standard chemotherapeutics.

Up until now, ferroptosis has not been fully understood. However, the importance of cellular suicide has already been impressively substantiated – for example, through apoptosis, which has been investigated in much more detail. Moreover, ferroptosis appears to play a role in inflammation and in cell survival under oxidative stress (e.g. in the nervous system). Previously only a small number of essential molecules such as glutathione peroxidase 4 (GPX4) were known to be involved in the ferroptosis process.

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,500 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

Rising life expectancy is causing an increase in age-related, but also sociological and environmental, influences on the genes. The Institute of Developmental Genetics (IDG) examines these changes in genetic material. In the Mouse Genetics group, genetic animal models are developed to investigate various diseases. These models are analyzed in the Disease Modelling research group in order to identify gene functions and cell processes and evaluate the influence of the environment and aging processes. The group focuses on the examination of neurological and psychiatric diseases.