Periodic Reporting for period 1 - NAP (twiN-on-a-chip brAins for monitoring individual sleeP habits)
Reporting period: 2023-03-01 to 2024-02-29
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).
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).
The efforts of the Consortium in the first 12 months of NAP project (as sketched in the GANTT in Figure 1) 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.
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.