Project description
Insight into the shape of the genome
The three-dimensional organisation of DNA is critical for gene activity, cell identity and responses to stress. Emerging evidence underscores the role of lamina-associated domains (LADs), regions of inactive DNA attached to the nuclear membrane that help organise the genome. Disruption of these structures may lead to ageing and cancer. With the support of the Marie Skłodowska-Curie Actions programme, the MorphoLADs project aims to create an atlas of LAD shapes during development. Researchers will employ Caenorhabditis elegans as a model organism to study how LAD patterns differ between cell types using advanced microscopy, AI and molecular mapping tools. Project findings will delineate how differences in LAD patterns impact function, revealing new principles of genome organisation and health.
Objective
The three-dimensional organization of the genome is emerging as a critical regulator of nuclear functions. But we are only beginning to define the diverse nuclear morphologies of different cell types and understand their cell-specific functions. To address this issue, I will focus on Lamina-Associated Domains (LAD), which are large heterochromatic domains anchored to the nuclear lamina. LADs help partition silent heterochromatin from active euchromatin enabling the tridimensional organization of the genome. These domains are crucial for gene silencing, cell signaling, and protecting DNA from UV damage, and their loss often leads to cellular dysfunction, for example in cancer or aging. Studies have shown that LAD morphologies vary considerably in different cell types. I propose to leverage the stereotyped development of C. elegans to generate an atlas of LAD morphologies through embryogenesis. In Aim 1, I will use an automated cell identification AI-based algorithm (ceSCALE, recently developed in the Mango lab) coupled with super-resolution microscopy to extract temporally evolving heterochromatin features across time and space, with a special focus on lamina-associated heterochromatin. I will complement this by defining cell-specific components near the lamina (TurboID, DamID) to uncover some of the governing rules that dictate the formation of specific LAD morphologies. In Aim 2, I will focus on a specific cell type that our preliminary data show contains unusual LADs: gut cells. I will relocate heterochromatin to the nuclear periphery of gut cells through ectopic tethering to determine whether changing gut LAD morphology affects its function. I hypothesize that the almost complete localization of heterochromatin in the interior of the nucleus of gut cells enables effective nuclear export and appropriated response to environmental cues. Altogether, MorphoLADs will define cell-specific LAD morphologies and open an avenue to explore their cellular functions.
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.
- natural sciences biological sciences genetics DNA
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences genetics genomes
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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)
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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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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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(opens in new window) HORIZON-MSCA-2025-PF
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4051 Basel
Switzerland
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