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 researchers 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.