Project description
X chromosome dosage in development and disease
Sex chromosomes play a crucial role in determining the phenotypic differences between males and females. However, their unequal gene copy distribution can lead to gene product imbalances. To address this, many species have evolved dosage compensation mechanisms, which equalise gene expression between the sexes. When this process fails, it can result in sex-specific disorders or lethality. In this context, the ERC-funded XDose project seeks to understand the mechanisms behind X monosomy-associated lethality by studying sex chromosome dosage in flies. By leveraging fly genetics and genomic techniques, the project will explore the roles of X chromosome dosage in development and its evolutionary significance across insect species, ultimately shedding light on its impact on health and disease.
Objective
Sex chromosomes are critical for controlling the phenotypic differences between males and females. However, they also create an imbalance in the gene products of sex-linked genes, with males having only one copy and females having two copies. To counteract this imbalance, many species evolved a chromosome-wide mechanism known as dosage compensation, which helps equalise gene expression between the sexes. This process is vital, as failed dosage compensation can lead to sex-specific disorders and lethality in several species including humans. Although researchers have made significant progress in understanding the mechanistic basis of dosage compensation, the core questions remain unanswered: why is the lack of X-chromosome compensation lethal and what are the physiological consequences of its absence?
The proposed research aims to identify the mechanisms underlying X monosomy-associated lethality by studying the genes, cells, and developmental processes sensitive to X chromosome doses. This question has been poorly investigated partly due to the difficulties of studying sex chromosome effects. To overcome this barrier, we will investigate flies as these permit the remarkable possibility of generating mosaic animals where sex chromosomes can be genetically manipulated in defined organs, and consequently, functional and molecular analysis.
Here, I will combine classical fly genetics, two novel model systems and cutting-edge genomic techniques to:
1. Identify the functions of X chromosome dosage in fly development.
2. Characterise the ancestral X chromosome compensatory system of all insects.
3. Discover the general shared functions of sex chromosome dosage in development using new insect model species.
Thus, results from this research should have a major impact on our understanding of the importance of sex chromosome dosage in physiology and disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine physiology
- natural sciences biological sciences zoology entomology
- natural sciences biological sciences genetics chromosomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-COG
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75794 PARIS
France
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