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Research / 11.04.2024
ERC grants Berlin scientists € 2.5 million each

(From left) Gary Lewin © Pablo Castagnola / MDC; James Poulet © Felix Petermann, Max Delbrück Center
(From left) Gary Lewin © Pablo Castagnola / MDC; James Poulet © Felix Petermann, Max Delbrück Center

Neuroscientists Gary Lewin and James Poulet at the Max Delbrück Center for Molecular Medicine have won highly coveted and competitive ERC Advanced Grants to study pain and the neural mechanisms that underlie temperature perception.

The European Research Council (ERC) has awarded Max Delbrück Center neuroscientist Professor Gary Lewin his third prestigious Advanced Grant of €2.5 million over five years to study how nerves in the skin become overly sensitive to mechanical stimuli and cause chronic pain. “The research could lead to new pain medicines, which are sorely needed,” says Lewin.

The ERC has also awarded Max Delbrück Center neuroscientist Professor James Poulet a €2.5 million Advanced Grant to study the relationship between core body temperature in mammals and their perceptions of external temperature. Poulet’s research is basic in nature and focuses on understanding how the healthy brain functions.

Perception of mechanical pain

Gary Lewin, Group Leader of the Molecular Physiology of Somatic Sensation lab, has been researching the perception of touch and pain for over 25 years. He is a pioneer in the study of the molecular mechanisms responsible for sensing mechanical pressure on the skin – a stroke or pinch for example – in mammals.

Earlier this year, Lewin and his team reported discovering a new ion channel – pores in cellular membranes through which charged biomolecules pass through to generate the electrical activity of cells. The ion channel, called Elkin1, is present in sensory endings in the skin. It plays an essential role in transmitting the sense of touch via nerve fibers to the brain. The study was published last month in the journal “Science.”

With his new Advanced Grant, Lewin now aims to use proteomic techniques that quantify all proteins in single cells to identify ion channels in skin involved in transmitting the sense of pain. “One of the approaches we want to take is to compare the proteomes of cells that transduce these persistent mechanical stimuli to cells that don't,” Lewin explains.

Hypersensitive nerves cause many types of chronic pain syndromes, says Lewin. For example, pressure sensitive nerve fibers may become hypersensitive to mechanical stimuli causing painful sensations to the slightest touch. “We want to find the distinctive molecules that are exclusively involved in the transduction of persistent mechanical painful stimuli,” he adds.

The research could lead to new types of pain treatments. It has been decades since a new pain medication has been introduced to the market, says Lewin, who developed an antibody-based pain treatment 28 years ago. The antibody was never marketed for use in humans but is now the basis of a medication given to dogs and cats suffering from chronic arthritis pain. Moreover, many existing pain medications do not provide sufficient relief for people suffering from chronic pain, he adds.

Lewin is thrilled to be among the selected awardees: “I’m very happy. It's so gratifying that the ERC felt that our project was both interesting and new, to fund me for a third time.”

Maintaining a healthy body temperature

How the brain perceives different types of sensory stimuli is a fundamental, but unsolved, problem in neuroscience. It has long been thought that the brain regulates internal body temperature and senses external temperatures via separate networks of neuronal cells, explains James Poulet, Group Leader of the Neural Circuits and Behavior lab. But Poulet’s research suggests this view is too simplistic.

In a research paper published in the journal “Nature” last year, Poulet and his colleagues identified the primary cortical representation of temperature, a “thermal cortex,” in a posterior region of the insular cortex. This region not only responds to external temperature, but may also compare core temperature with skin temperature to create a signal by which the brain perceives the difference between the two.

“Rather than being completely separate systems, we think that brain networks that control our core physiology and those that sense the environment communicate closely with each other,” Poulet says.

With his Advanced Grant, Poulet and his colleagues will compare human and mouse, which are warm-blooded, to naked mole-rats, which are cold-blooded, to identify the cellular networks that integrate sensory and core body-state information. The researchers plan to use a combination of techniques that include neural recordings and anatomical tracing, which identifies connections between brain areas.

Poulet’s lab also plans to study individual differences in core body temperature and how they contribute to differences in perception of external temperature – a phenomenon that may explain why one person might feel the need to wear a jacket when the outside temperature is 15 degrees Celsius, while another is comfortable in a T-shirt.

Although the research will have implications for diseases that involve disrupted physiology, Poulet is more focused on studying how the brain works. “Understanding the healthy brain is how we're going to solve brain diseases in the long term,” he says.

Poulet is “happily surprised and excited,” at having won an Advanced Grant. “It's a real honor.”

www.mdc-berlin.de

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