Descripción del proyecto
Descifrar el papel de la interacción celular en las enfermedades neuromusculares
Los trastornos neuromusculares son las enfermedades neurológicas con menos posibilidades de tratamiento y son causadas por defectos en las células de la unidad neuromuscular: los neurogliocitos y los miocitos. El proyecto financiado con fondos europeos AxoMyoGlia abordará el ambicioso objetivo de dilucidar la relación espacial y molecular funcional entre las células de la unidad neuromuscular. La investigación se centrará en neuropatías periféricas desmielinizantes y empleará modelos murinos de neuropatías para generar un interactoma celular transcripcional de la unidad neuromuscular enferma a un nivel de resolución de célula única. El proyecto pretende desvelar los mecanismo patológicos que serán relevantes para el desarrollo de estrategias terapéuticas para las enfermedades neuromusculares.
Objetivo
Neuromuscular disorders belong to the most common but least treatable neurological conditions and are caused by defects in cell types that together build the neuromuscular unit – motoneurons and their axons, glial cells and myocytes. Clinically, neuromuscular diseases share an impairment of motor function and the intimate functional relationship of involved cell types suggests overlapping pathological mechanisms. As our current understanding is largely confined to locally isolated processes, the present AxoMyoGlia proposal will undertake the ambitious approach to elucidate the spatial dimensions of the molecular interplay among the key cellular players of the neuromuscular unit. By taking demyelinating peripheral neuropathies as a powerful model system, I aim at unravelling basic principles of how local glial impairment propagates malfunction within the neuromuscular unit, including potential remote axon and muscle feedback mechanisms. To this end, I will employ neuropathic mouse models and generate a holistic transcriptional cellular interactome of the diseased neuromuscular unit at single cell resolution level. With milli- to nanometer imaging precision, this interactome will be extended to the first visualization of the spatial relation between glial and axonal dysfunction along the entire longitudinal dimension of the nerve. In order to untangle local and distant causes from consequences, I will develop an innovative mouse model that will offer the unprecedented option to specifically induce and examine the global consequences of locally restricted glial neuropathy at any position in the neuromuscular system. With its pioneering multimodal approach to converge different areas of neuromuscular research, AxoMyoGlia aims at uncovering general pathological mechanisms at the interface of basic neuroscience and applied neurology - that will be highly relevant for therapeutic advance in neuromuscular diseases and related disorders of the central nervous system.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
04109 Leipzig
Alemania