Project description
Improved neuromuscular organoids
Organoids are 3D miniature models of human organs grown in the lab that mimic key aspects of tissue structure and function. They offer powerful tools for studying tissue-specific physiological and pathophysiological processes. With the support of the Marie Skłodowska-Curie Actions programme, the NanoMag organoids project focuses on neuromuscular organoids (NMOs), which replicate the intricate interactions between nerves and muscles. However, NMOs fail to mature fully in the absence of external neuronal stimuli or mechanical force. To overcome this, researchers will develop nano-force methods to stimulate NMOs and recreate brain-muscle connections. The generated NMOs will be used to study spinal and bulbar muscular atrophy, providing new insights into the cause of this neuromuscular disease.
Objective
*Neuromuscular disorders, whose incidence and prevalence have increased over time have currently no cure, and understanding their pathological mechanisms remains challenging due to the lack of reliable human in vitro models. A groundbreaking approach involves human 3D trunk neuromuscular organoids (NMOs) that replicate the cellular diversity and the functional dynamics of the neuromuscular system. However, the absence of in vivo-like external stimulations leads to reduced contractions and prevent terminal maturation, restraining their applicability for studying long-term neuromuscular diseases. The primary goal of this project is to design innovative multi-disciplinary approaches to mimic in vivo mechanical and brain inputs and provide new paradigms for organoid generation. A new method will be developed to apply spatiotemporally controlled nano-forces within NMOs, with the aim of enhancing the maturation of both the neural and muscle tissue. Additionally, magnetically induced nano-forces will be exploited to guide the reconstruction of the corticospinal tract within newly generated cerebral-NMOs and integrate brain inputs. Cutting-edge imaging, optogenetics, and single-nucleus RNA sequencing will be used for in-depth characterization of the outcomes. The hypothesis is that these stimuli will significantly promote NMOs maturation, resulting in a more sophisticated model for neuromuscular disease research. As case-study, the enhanced NMOs will be applied to model and explore the complex pathological mechanisms of X-linked spinal and bulbar muscular atrophy (SBMA). Patient-derived nano-forced cerebral-NMOs will be generated to investigate the impact of SBMA on neuromuscular system and corticospinal tract. Supporting this project will enable the implementation of innovative methodologies for the optimization of a relevant human in vitro system, with the potential to revolutionize research and treatment approaches for neuromuscular diseases.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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13125 Berlin
Germany
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