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

Project Information

NAP

Grant agreement ID: 101099310

DOI

10.3030/101099310

EC signature date 16 December 2022

Start date 1 March 2023

End date 28 February 2027

Funded under

• The European Innovation Council (EIC)

Total cost

€ 3 615 375,00

EU contribution

€ 3 615 375,00

Coordinated by

UNIVERSITA DI PISA
Italy

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

Reporting period: 2024-03-01 to 2025-02-28

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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.