image: Gary R. Lewin's focus is on understanding the anchoring of ion channels. view more
Credit: Anyess von Bock / MDC
Basic researchers Gary Lewin and Norbert Hübner are investigating the molecular mechanisms underlying neurological and heart diseases. Their focus is on understanding the anchoring of ion channels and micropeptides in heart muscle cells.
Tethered ion channels
The European Research Council (ERC) has awarded MDC research Gary R. Lewin an Advanced Grant worth 2.5 million euros. After receiving an ERC Advanced Grant in 2011 and an ERC Proof of Concept Grant in 2016, the scientist, who has been working at the MDC since 1996, is now the recipient of coveted ERC funding for the third time.
Lewin and his research team are attempting to understand how the sense of touch works and how neurons perceive mechanical stimuli. It is already known that when skin is touched, an electric signal is generated in the ion channels of the neuronal membrane. Similar to ships moored in a harbor, ion channel proteins are tied to the surrounding connective tissues and can as a result feel the "swell of the waves" in their periphery. But researchers still haven't discovered what these molecular tethers are made of.
The research project aims to identify ion channel anchors and characterize them at the molecular level. The scientists also want to find out how these anchors can be untethered in a targeted and reversible way. Through mouse and human studies, they hope to lay the groundwork for therapies that address tactile disorders.
Small proteins and heart failure
More than 20 million people worldwide suffer annually from heart failure. One in five patients die within a year. MDC scientist Norbert Hübner and his team will use the ERC Advanced Grant, which is worth 2.3 million euros, to decipher the molecular mechanisms underpinning this serious disease.
They are taking an entirely new approach - one that involves small proteins called micropeptides. These are being produced from RNAs, which were previously considered to be of no significance to the heart and its diseases. The researchers will attempt to answer questions such as: Which genes encode micropeptides? What are their functional roles in the heart or in heart cells? And how are they involved in heart failure?
Since heart muscle can't be easily studied in vitro, the scientists are using pluripotent stem cells (PSCs) to study heart muscle functions in cell models, looking into the ability of heart cells to contract and how it is affected by micropeptides. Some of these molecules can leave the cell, where they can communicate with other cells. The researches will therefore study if some of the small proteins act upon neighboring cells of connective tissue. Extensive growth of connective tissue plays a key role in development of heart failure, but the mechanisms that drive this process are mostly unknown.
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About ERC grants
The funding program of the European Research Council (ERC) is one of the most important in Europe. Since 2009, ERC Advanced Grants have covered all scientific disciplines. Recipients are awarded up to 2.5 million euros for a period of five years. MDC researchers have so far received a total of 22 ERC grants, nine of which have been Advanced Grants.
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) was founded in Berlin in 1992. It is named for the German-American physicist Max Delbrück who was awarded the 1969 Nobel Prize in Physiology and Medicine. The MDC's mission is to study molecular mechanisms in order to understand the origins of disease and thus be able to diagnose, prevent and fight it better and more effectively. In these efforts the MDC cooperates with the Charité - Universitätsmedizin Berlin and the Berlin Institute of Health (BIH) as well as with national partners such as the German Center for Cardiovascular Research and numerous international research institutions. More than 1,600 staff and guests from nearly 60 countries work at the MDC, just shy of 1,300 of them in scientific research. The MDC is financed by the Federal Ministry of Education and Research (90 percent) and the State of Berlin (10 percent) and is a member of the Helmholtz Association of German Research Centres.