twiN-on-a-chip brAins for monitoring individual sleeP habits

Información del proyecto

NAP

Identificador del acuerdo de subvención: 101099310

DOI

10.3030/101099310

Fecha de la firma de la CE 16 Diciembre 2022

Fecha de inicio 1 Marzo 2023

Fecha de finalización 28 Febrero 2027

Financiado con arreglo a

• The European Innovation Council (EIC)

Coste total

€ 3 615 375,00

Aportación de la UE

€ 3 615 375,00

Coordinado por

UNIVERSITA DI PISA
Italy

Periodic Reporting for period 2 - NAP (twiN-on-a-chip brAins for monitoring individual sleeP habits)

Período documentado: 2024-03-01 hasta 2025-02-28

Resumen del contexto y de los objetivos generales del proyecto

Insufficient sleep is an under-reported epidemic and sleep disturbances are common early signs of neurodegeneration. Clinical research is currently challenging the assumption that human sleep is a one-fits-all phenomenon: breaking new grounds into sleep research is needed. NAP aims at exploiting advanced models of the human brain, the so-called cerebral organoids, for studying sleep and its alterations.

Thanks to human induced pluripotent stem cells, organoids will allow the study of individual sleep habits. During the project we will experimentally evaluate the metabolism and the mass of the cerebral organoids since these parameters are known to be intimately linked to sleep/wake rhythms. We will exploit this information for cyclically awakening the cerebral organoids, following the physiological rhythms, but also simulating sleep deprivation. We will use mice and calcium imaging for finely characterizing sleep and wake functional dynamics. Moreover, we will correlate the sleep and time times with the ones extracted in humans with wearable sleep trackers. Thanks to a new device purposely developed during the project, for the first time we will be able to monitor the electrophysiological activity of all the neurons in their 3D arrangement within the cerebral organoids. Using this purposely developed technology, we will identify the effects of sleep deprivation and the early-stage and sleep-related symptoms of neurodevelopmental disorders, such as Parkinson’s’ disease.

NAP starts on March 1st, 2023, with an international and multidisciplinary consortium, with different expertise, ranging from biomedical engineering to biotechnologies, from microfabrication to signal processing. The consortium, coordinated by the University of Pisa, is composed of the Freiburg University (Germany), the University of Amsterdam (Holland), and the SMEs, Organotherapeutics Gmbh (Luxembourg), Atlas Neuroengineering (Belgium) and SleepActa (Italy). From September 2024, thanks to the NAP HOP-ON project (funded within the HORIZON-WIDERA-2023-ACCESS-06 call for proposals), a new Beneficiary (STU) was included. STU is in charge of designing a new device for e-home sleep monitoring: this will lead to the collection of more data from both healthy volunteers and PD patients.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

The efforts of the Consortium in the first 12 months of NAP project (as sketched in the GANTT in the DoA) were directed toward: i) setting up the technical, scientific and financial management procedures among the Beneficiaries ii) recruiting the personnel necessary for conducting the research, iii) getting the necessary equipment for conducting the research proposed (e.g. the two-photon microscope for calcium imaging at UVA), and iv) planning and performing Communication, Outreach, Dissemination and Exploitation activities tailored for any possible stakeholders of our future outcomes.


The efforts of the Consortium in the first 24 months of NAP project (as sketched in the GANTT in DoA) were directed toward: i) measuring organoid mass and metabolism of whole brain organoids generated from cells of healthy individuals and PD patients carrying two different mutations, to identify the proper sleep-to-wake timing for those constructs, ii) performing preliminary tests for inducing the wake state in organoids using a drug stimulation, iii) prototype the 3D MEA and test it for cell compatibility. Regarding the non-scientific tasks, we are: i) conducting the technical, scientific and financial management among the Beneficiaries, along with the support tailored at the new beneficiary ii) conducting the experimental procedures thanks to the pipelines developed in the first year of the project, iii) performing Communication, Outreach, Dissemination and Exploitation activities tailored for any possible stakeholders of our future outcomes and iv) integrating the new partner and the additional activities within the whole consortium.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

In the first period (12 months) we extensively worked on setting up the experimenta setups for perfoming different activites going beyond the state of art, e.g. a new setup for measuring the metabolic rates in advanced in vitro construct and monitoring the calcium dynamics, the design and prototype of new electrodes array for ephysio monitoring.

In the second period, we extensively worked on exploiting the experimenta setups for perfoming the different activites envisioned, e.g. measuring the metabolic rates in advanced in vitro construct, monitoring the calcium dynamics, inducing the wake state in vitro, designing and prototyping new stackd electrodes array for ephysio monitoring.