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PLEC2022-009171

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Granja in vitro: desarrollo del primer biobanco de organoides de animales de gra...

Granja in vitro: desarrollo del primer biobanco de organoides de animales de granja como alternativa a los experimentos con animales en la investigación de enfermedades infecciosas (FARMBANK) Animal experiments are a ubiquitous component in biomedical research, but there is a growing ethical and societal demand to reduce, refine, and ultimately replace them. However, this demand to reduce animal experiments in research... ver más

01/01/2022

INSTITUT DE RECERC...

555K€

Presupuesto del proyecto: 555K€

Líder del proyecto

INSTITUT DE RECERCA I TECNOLOGIA AGROALIMENTA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5 | 520K€

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2022-01-01 No tenemos la información de la convocatoria

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Líder del proyecto

INSTITUT DE RECERCA I TECNOLOGIA AGROALIMENTA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5 | 520K€

Presupuesto del proyecto 555K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Animal experiments are a ubiquitous component in biomedical research, but there is a growing ethical and societal demand to reduce, refine, and ultimately replace them. However, this demand to reduce animal experiments in research clashes with the increasing demand for animal models to tackle emerging biomedical challenges. Thus, we are in dire need of alternative experimental systems that reduce the demand for animal experiments. One promising alternative are organoids, which are multicellular 3D structures grown from stem cells obtained from live tissues. Organoids can be readily cultivated in vitro and at high throughput while maintaining many physiological features of their tissue of origin, making them an attractive potential alternative to animal models. However, most current efforts are restricted to organoids derived from human cancer tissues, which are of limited use in other areas, such as infectious disease research. Moreover, efforts to generate organoids from other species (i.e., domestic animals) are currently still at the pilot stage (few animals per study), and thus do not capture the genetic variability found in these populations.In this project, we will tackle these issues by developing the first comprehensive organoid biobank tailored to infectious disease research. To establish this biobank, we will use the domestic pig as our starting point, motivated by its close relationship to human physiology, its function as a mixing vessel for many zoonotic diseases, and its commercial importance in Spain. As our case study, we will largely focus on coronaviruses, a group of virus species with high affinity to pigs and with large zoonotic potential. In the project, we will pursue four objectives. First, we will generate a comprehensive biobank of porcine organoids from three tissues that are particularly important for infectious diseases (nose, lung, and gut). Overall, we aim to generate organoids from 100+ individual animals, covering all important breeds/herds in Spain. To enable the envisioned scale of this biobank, we will leverage our previous experience in generating gut and lung organoids. Moreover, to characterize this organoid biobank we will make use of a high-throughput imaging facility that we are currently establishing at our institute with funding from the Spanish Government.Second, we aim to provide a proof-of-concept that this organoid biobank is a valuable resource guiding antiviral drug development. Towards this end, we will leverage a unique library of lead compounds with antiviral effect against coronaviruses such as SARS-CoV-2 developed by our industry partner PharmaMar. We will assess the impact on viral replication and tissue health using high-throughput imaging. Third, we aim to use this organoid biobank to better understand the principles by which coronaviruses become resistant to antiviral treatment. Towards this end, we will perform serial passage experiments with concomitant antiviral treatment using our organoid biobank. We will then use deep sequencing of adapted virus populations to identify mutations driving this drug resistance.Fourth, we will expand our biobank to other domestic animals with commercial importance in Spain, in particular chicken and ruminants. Towards this end, we will apply lessons learned in objectives 1-3 to modify organoid generation and benchmarking. We envision this farm-in-a-plate will be a unique resource not only in Spain, but world-wide, with tremendous potential for reducing animal experimentation.In conclusion, this project is made possible by the unique combination of expertise among diverse academic and industrial partners and will serve as a blueprint for the development and usage of animal organoid biobanks for infectious disease research and beyond.

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