Project description
When the inner ear loses its sense of gravity
Microscopic crystals in the inner ear shift with gravity to inform the human brain which way is up. Vertigo and disorientation can result when the crystals break down. However, little is known about why these balance disorders occur or how to treat them. To find answers, the ERC-funded OTOREG aims to study the axolotl, a salamander famous for its ability to regrow lost limbs. More importantly, its inner ear is highly similar to a human ear. When the axolotl loses its gravity-sensing crystals, it loses its balance. However, it can regrow the crystals. The project will track this recovery process at a molecular level to determine whether repair is possible in humans.
Objective
Gravity deeply impacts all life on Earth. Organisms sense its directionality and use it for orientation. In tetrapods, the gravitational sense relies on biomineral crystals, known as otoconia, in our inner ear. Their movement is detected by sensory cells, transduced into a neural output, and interpreted by the brain. Deterioration of the otoconia can cause severe balance issues, contributing to diseases collectively referred to as vestibular disorders. Yet, the processes driving both otoconia formation and degradation remain unclear. Limitations in diagnosis of balance disorders in humans stem from the inaccessibility of the inner ear for studying which components are functioning deficiently. In this context there is a need to develop models of vestibular function, disease and restoration. The ultimate goal of OTOREG is to uncover fundamental mechanisms underlying gravity sensation, using the axolotl as a model of regeneration and balance disorders.
The morphology of the salamander inner ear is strikingly similar to mammals and my preliminary data indicates that removal of otoconia leads to a balance disorder phenotype. Otoconia then regenerate in the axolotl, restoring correct swimming behaviour and providing a functional readout. This system thus permits a holistic, multilevel approach to understand gravity sensation: I) At the biomaterial level, using structural methods to investigate crystal development and regeneration; II) at the molecular and cellular level, to characterize the genes and cells that drive the formation of the sensory apparatus; and III) at the organismal level, using the behavioural readout to test compounds which might contribute to the degeneration or restoration of otoconia. This detailed understanding of the gravity sensation organ can provide a platform for studying and developing therapeutical approaches for balance disorders to improve people’s quality of life, as well as to probe the fascinating biology of our most ancient sense.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2025-STG
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01069 Dresden
Germany
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