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Human skeletal muscle organoids to identify novel biomarkers and therapeutics in personalized medicine for sporadic inclusion body myositis

Group: Biosensors for bioengineering
Group leader: Javier Ramon Azcon ( jramon@ibecbarcelona.eu)

Research project

Sporadic inclusion myositis (sIBM) is a rare disorder (OMIM 147421) that becomes the most common myositis in the over-fifties adult population. The disease is characterized by distal and proximal progressive skeletal muscle weakness and atrophy that produces severe disability. At present, there is still non-known etiology, non-effective biomarkers, nor treatments for sIBM patients, among others, due to the lack of useful models of disease. Animal models and classical in vitro 2D-cell cultures usually set the path to depict pathogenic molecular mechanisms and advance in disease breakthroughs. However, serious concerns exist regarding how faithfully these 2D-cell models reproduce the biological complexity of the target tissue in the case of muscle and how the human mechanism of disease is recapitulated in animals. Biofabrication tools can be applied to engineer human three-dimensional (3D) culture systems that complement current preclinical research models.

This project will develop patient-derived sIBM muscle organoids harboring patient genetic, epigenetic, and environmental cues and monitor real-time responses to therapeutic candidate drugs of a muscle-on-a-chip device (MoC). We aim to test in sIBM-MoCs drug hits selected from repositories of therapeutic candidates depending on the deregulated pathways found in sIBM patients by screening patients’ exome, transcriptome, proteome, and metabolome.

The project will be an interdisciplinary project coordinated by IBEC (Prof. Javier Ramon) and with the participation of the Hospital Clinic de Barcelona (MD. Josep Maria Grau Junyent and Dr. Gloria Garrabou).

Job position description

Our central hypothesis is that patient-derived 3D cultures of skeletal muscles will contribute to elucidating the molecular pathways of the disease and predict in a much more precise way than conventional cell culture and animal models the response to

candidate therapeutics. This hypothesis is supported by technological developments (MoCs devices and biosensors) that make possible real-time determinations of drug responses. We additionally hypothesize that the OMICs’ characterization of sIBM patients (study of the exome, transcriptome, proteome, and metabolome) will help to depict deregulated pathways in disease that will offer (i) to deepen in disease etiology, (ii) to identify diagnostic/prognostic biomarkers and (iii) to select therapeutic targets and pharmacologic candidates that will be tested in the MoCs device. Combining the MoCs and OMICs technology will fill the gap currently existing in the preclinical research in sIBM, which completely lacks this type of approach.

The Ph.D. student will be in charge of the 3D skeletal muscle development and the design and fabrication of a suitable microfluidic device to cultivate and monitor functional human skeletal muscle tissue. Finally, the Ph.D. student will screen therapeutic targets and pharmacologic candidates in the MoCs device.