Project description
Chromosome architecture emerges in population variation
The DNA strand in each eurkaryotic cell, when unravelled, is 2 m long. Folded precisely in the nucleus, its 3D configuration is crucial to maintain correct gene transcription. To determine what effect 1D variation has on 3D genome variation, the EU-funded project POPARCH has assembled a unique cohort of 100 chickens raised in a controlled environment, the largest in vivo animal study to date. The researchers will develop a catalogue of DNA sequence variants to determine how non-coding DNA variants can control 3D genomic structure. This study promises to be the unique blueprint for further studies including testing new drug therapies on humans without interference from other variables.
Objective
The linear one-dimensional (1D) DNA fiber inside each Eukaryotic cell nucleus folds into a precise three-dimensional (3D) structure, whose structural preservation is vital for correct cell homeostasis and gene-regulatory mechanisms. Previous studies showed that if 3D structure is altered, aberrant phenotypes and diseases can arise. However, little is known on how 1D variation can affect 3D genome variation. Although recently developed technologies allow researchers to generate data to characterize the 3D structural patterns, as of yet no studies have systematically examined how this affects inter-individual 3D variation. I hypothesize a substantial fraction of 3D genome structural variation is controlled through 1D variation, affecting gene expression, and lastly phenotypes. I will test this by quantifying 1D and 3D genomic variation from 100 individuals selected from a chicken cohort my host raised under extremely well-controlled environmental conditions, making it the largest study of its kind up to today, and the first to use an in vivo animal model. Then, computationally I will develop an analytical framework and produce a catalog of DNA sequence variants that condition 3D genome structure. Upon executing my research, I expect to provide a new explanation on how non-coding DNA variants can exert their effect, thus offer new testable hypotheses to researchers interested in genotype-phenotype transitions. This is a proof-of-concept project and, should I be correct, will open a door to expansion in other species, including humans, with a large potential use in medical genomics, thus facilitating pharmacological interventions by disentangling causal intermediate processes. By combining my 3D genomics expertise with the host’s population-statistical genomics knowledge, on his unparalleled cohort of chickens, I will develop unique expertise to place me as the pioneer of a completely new, multidisciplinary field.
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.
- engineering and technology materials engineering fibers
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
- medical and health sciences basic medicine physiology homeostasis
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
Funding Scheme
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2021-PF-01
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1165 KOBENHAVN
Denmark
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