Blood Vessel Development and Homeostasis: Identification and Functional Analysis of Genetic Modifiers

Informacje na temat projektu

ZMOD

Identyfikator umowy o grant: 694455

DOI

10.3030/694455

Projekt został zamknięty

Data podpisania przez KE 21 Czerwca 2016

Data rozpoczęcia 1 Października 2016

Data zakończenia 30 Września 2021

Finansowanie w ramach

• EXCELLENT SCIENCE - European Research Council (ERC)

Koszt całkowity

€ 2 500 000,00

Wkład UE

€ 2 500 000,00

Koordynowany przez

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

Periodic Reporting for period 4 - ZMOD (Blood Vessel Development and Homeostasis: Identification and Functional Analysis of Genetic Modifiers)

Okres sprawozdawczy: 2021-04-01 do 2021-09-30

Podsumowanie kontekstu i ogólnych celów projektu

Genetic robustness refers to the ability of organisms to withstand mutations, showing little or no phenotype, or compromised viability. Our studies on genetic robustness are specifically trying to understand mechanisms of genetic compensation, which is defined as ‘changes in RNA or protein levels that can functionally compensate for the loss of function of another gene’. This work is important for society because it will allow one to better understand phenotypic variability within the human population, in other words, why people with the same mutation often exhibit very different phenotypes. In addition, our work aims to identify genes that can functionally compensate for the loss of function of another gene in the context of certain vascular diseases. In terms of the conclusions of the actions, work done during the funding period has clearly shown the importance of the new mode of genetic compensation we uncovered, as well as its complexity.

Prace wykonane od początku projektu do końca okresu sprawozdawczego oraz najważniejsze dotychczasowe rezultaty

This project started with our efforts to understand the phenotypic differences between knockout (mutant) and knockdown (antisense treated) phenotypes in zebrafish embryos, leading to the publication of a paper entitled ‘Genetic compensation induced by deleterious mutations but not gene knockdowns’ (Rossi, Kontarakis et al., 2015). Since these initial observations, which have attracted a lot of attention, we have been working to understand underlying mechanisms and published follow up papers entitled ‘Genetic compensation triggered by mutant mRNA degradation’ (El-Brolosy et al., 2019), and ‘Transcriptional adaptation in C. elegans’ (Serobyan et al., 2020), as well as several reviews (El-Brolosy and Stainier, 2017; Sztal and Stainier, 2020; Kontarakis and Stainier, 2020; Jakutis and Stainier, 2021).

Innowacyjność oraz oczekiwany potencjalny wpływ (w tym dotychczasowe znaczenie społeczno-gospodarcze i szersze implikacje społeczne projektu)

Many mechanistic questions remain to be answered of course, and so we are continuing these studies using a variety of state-of-the-art approaches in different model organisms as well as in mammalian cells in culture.

mRNA degradation