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.
Fields of science
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
35122 Padova
Italy