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On-chip metasurface-based neuroimaging platform toward high-throughput drug screening in freely behaving animal

Project description

Moving zebrafish into the realm of high-throughput drug screening systems

Scientists often rely on simplified model systems to get a handle on complex topics relevant to human health and disease. The zebrafish has emerged as a very potent model system. It shares many of the tissues and organs of humans, a large percentage of the same genes (its entire genome has been mapped), and its optically transparent larvae facilitate the relatively simple visualisation of many processes in a behaving animal. However, its utility in drug screening is somewhat limited by the need for high-throughput methodologies. The EU-funded FLAMMES project is developing techniques for the optical whole-brain imaging of multiple freely behaving zebrafish larvae in parallel. The project aims to open the door to the use of this extremely versatile model system in high-throughput drug screening that evaluates both neurophysiological and behavioural effects.

Objective

A central goal of modern neuroscience is to correlate neurological conditions, external stimuli and behavior with the activity and location of individual neuron within a large brain volume. Thus, simultaneous recording of brain activity and organism behavior are fundamental to characterize circuit alterations underlying neurological disorders and to assess potential attenuation strategies. Thanks to the high degree of morphological, genetic and behavioral resemblance with humans, zebrafish is becoming a prominent model for studying neurological disorders and screening of neurospecific compounds. Owing to reduced light scattering, small size and 3R-principle compatibility of the zebrafish larvae, parallel whole-brain neuroimaging of multiple zebrafish might pave the way of in vivo drug discovery. Recent studies report technological breakthroughs that enable monitoring of zebrafish whole brain activity with cellular resolution. Although widely used for functional imaging, larval zebrafish remains limited to manual, extremely challenging and low-throughput screening.
Here, I propose to integrate my solid background in biophysics and micro-nano optics engineering with new skills I will build at the Host Institution and Secondment for the project success. Goal of this project is to enable optical whole-brain imaging of multiple zebrafish larvae (Danio Rerio) freely behaving. First, I will demonstrate zebrafish larva neuroimaging with a novel metasurface-based optical sectioning illumination (Aim 1). Second, I will demonstrate selective plane on-chip detection synchronized with the excitation plane (Aim 2). Finally, I will prove potential parallel larvae on-chip microscopy (Aim 3). The proposed neuroimaging concept is a flexible approach to perform high-throughput drug screening based on recordings of the brain activity and characterization of the behavior outcome. Collectively, this study will provide a platform that contribute bridging the gap from bench-to-bedside.

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Topic(s)

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERSITA DEGLI STUDI DI PADOVA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 183 473,28
Address
VIA 8 FEBBRAIO 2
35122 PADOVA
Italy

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Region
Nord-Est Veneto Padova
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 183 473,28
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