Spotlight for ERC Advanced Grant awardees Magdalena Götz and Marcus Conrad
Wanted: Established, leading principal investigator with a track-record of significant research achievements in the last 10 years. Found: At Helmholtz Zentrum München. Magdalena Götz and Marcus Conrad both receive an ERC Advanced Grant for their outstanding scientific work. The European Research Council (ERC) will fund their projects with more than 2 million Euros each for the next 5 years.
NeuroCentro – “If we succeed to continue neurogenesis into adulthood, this could be a groundbreaking step for brain repair.”
Magdalena, this is the second time you receive an ERC Advanced Grant for your research on neurogenesis. What is the goal of your new project NeuroCentro?
Magdalena: Usually, new neurons are generated in the embryonic stage only. Our final goal with NeuroCentro is to expand the timeframe of neurogenesis to adulthood. This would give us the opportunity to reactivate the generation of new neurons for brain repair in patients. Before we get to this point, however, we first need to understand the mechanisms of ongoing neurogenesis better. We hope that our latest findings about the unique centrosome composition of neural stem cells will help us in this matter.
What makes the centrosome so interesting for your research?
Magdalena: The centrosome is a crucial cellular organelle involved in many functions of the cell cycle such as cell division. Some brain diseases can be linked to mutations in centrosome-associated proteins. The reasons why these protein mutations affect the brain development and function are still quite unknown. One exemption: Together with the Proteomics Core Facility at Helmholtz Munich, my group has screened centrosome components in human neural stem cells and has identified specific proteins which can be associated with a neuronal migration disorder called periventricular heterotopia in which nerve cells fail to migrate to their proper position. This might help to decipher the role of specific proteins at the centrosome and their contribution to neurodevelopmental disorders in general.
What are your next steps?
Magdalena: We will continue working on periventricular heterotopia and aim to reactivate centrosome components and induce cell migration. These results will be of major importance for each disease condition due to misplaced cells. In a next step, we aim to utilize Cas9 (CRISPR associated protein 9) genetic engineering to maintain the neural stem cell specific centrosome composition beyond the end of neurogenesis. This aims to allow adequate cell division and migration sustainably. If we succeed to continue neurogenesis into adulthood, this could be a groundbreaking step for brain repair.
IRONDEATH – “With ferroptosis, we will likely be able to prevent age-dependent degenerative diseases or even fight cancer in the near future.”
Marcus, what is your project IRONDEATH about?
Marcus: When we talk about “iron death”, we refer to a quite recently described phenomenon known as “ferroptosis” – a natural and non-apoptotic form of iron-dependent cell death which is marked by the oxidative destruction of cellular membranes. The reason why we talk about this are the numerous possibilities that ferroptosis offers for pharmacological intervention. Once we gain sufficient control over this distinctive form of cell death, we will soon be able to prevent age-dependent (neuro)degenerative diseases or even fight difficult to treat cancer. But first we need to improve our current understanding of the processes ultimately driving ferroptosis. Since the first mentioning of ferroptosis as a novel form of cell death in 2012, we have made great strides to better understand the molecular processes underlying this form of cell death. Actually, my group has made a series of landmark discoveries that provided disruptive new insights about ferroptosis in the recent years.
What questions do you want to address with this project?
Marcus: First of all, we aim to uncover whether there are still yet-unrecognized key ferroptosis nodes that may explain why certain cells are highly vulnerable to ferroptosis while others are not. Also, we need to better comprehend the nature and subcellular compartment where the initial ferroptosis priming signal is being generated as this knowledge is crucial to understand the entire process. And ultimately: Why do certain cells die by apoptosis and others by ferroptosis? Only dedicated basic research can provide answers to all of these questions.
Looking 5 years into the future: Where will you stand with your research on ferroptosis?
Marcus: I believe that in 5 years’ time we might be able to finally decipher and localize the ferroptosis death signal and understand why some cells are prone to undergo ferroptosis while others succumb to alternative cell death routines. This knowledge should guide us on the way to design ferroptosis-based precision treatments for patients suffering from early cell loss and tissue demise or therapy-resistant tumors and metastasis.
Learn more about this year’s ERC Advanced Grant: <link erc.europa.eu/news/erc-2019-advanced-grants-results - extern>https://erc.europa.eu/news/erc-2019-advanced-grants-results</link>