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Genetic Design of Biological Time in Fish

Project description

New tools to understand the pace of life in vertebrates

The pace of life of each species determines the duration of embryonic development, onset of puberty, and rate of ageing. However, it remains unclear why these traits vary so greatly between different species. The long lifespans of classical vertebrate models have impeded progress in this area until now. The EU-funded AquaAgeRate project aims to develop tools to study how the pace of life is regulated in vertebrates, with a focus on killifish species. These fish species exhibit up to a 10-fold difference in lifespan, making them an ideal model for studying life-history adaptations. Understanding the pace of life could have far-reaching implications, including rrevolutionizing ageing management, treating related diseases, and improving in vitro fertilization and commercial aquaculture.

Objective

Every species experiences a unique pace-of-life, which determines the duration of its embryonic development, onset of puberty, and rate of aging. However, how these traits are scaled so differently between species is largely unknown. Here, I propose to develop the tools to systematically study how the pace of life is regulated in vertebrates. To date, progress in our understanding has been experimentally hindered by the relatively long lifespans of classical vertebrate models. To address this challenge, I recently pioneered a genetic platform for rapid exploration of aging in the naturally short-lived turquoise killifish.

Killifish species display up to 10-fold differences in their lifespan, thus providing a microcosm of extreme life-history adaptations. Here, we will significantly advance the state of the art by transforming selected species into genetic models. Specifically, we will use unbiased chemical screens to explore the molecular switch that allows killifish development to be suspended for years, in a process called diapause. We will then use our findings to establish genetic control of diapause and the aging processes that co-evolved in this clade. Interrogation of the transcriptional networks in play will be made possible by developing a CRISPR screen platform for fish cells. Finally, we will explore the co-regulation of rapid puberty and compressed lifespan in killifish, by developing multiplexed and reversible genetic approaches.

Aging is the primary risk factor for many human pathologies. Thus, developing a quantitative and mechanistic understanding of the pace of life could revolutionize the way we manipulate aging, treat related diseases, and even control complex traits. Identifying such new principles will also have a broader impact, such as affecting developmental rates in in-vitro fertilization. Furthermore, providing precision genome editing tools for fish, and accelerating the generation time will greatly impact commercial aquaculture.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2022-STG

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Host institution

THE HEBREW UNIVERSITY OF JERUSALEM
Net EU contribution
€ 1 500 000,00
Address
EDMOND J SAFRA CAMPUS GIVAT RAM
91904 Jerusalem
Israel
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 500 000,00

Beneficiaries (1)