Project description
New molecular insight into chromosome dynamics
The formation and segregation of chromosomes during mitosis involves the shortening and thickening of the DNA. Protein complexes including condensin play a central role in chromosome dynamics during this process. However, the molecular mechanisms behind the function of condensin remain unclear. With the support of the Marie Skłodowska-Curie Actions programme, the Chromofold project will utilise a computational approach to study condensin-mediated chromatin folding and build a comprehensive model of condensin function. Researchers are interested in understanding if condensin is implicated in pulling DNA into loops or clustering DNA segments together in a process known as bridging-induced phase separation (BIPS). Project results will help delineate how disruption of condensin complexes may cause chromosome instability.
Objective
In human cells, the SMC complex condensin plays a significant and essential role in chromosome condensation, but there is conflicting data. Studies from other groups have suggested that the loop extruding activity of condensin is important for chromosome folding, but a study from my host lab suggested that loop extrusion (LE) alone is not able to package chromosomes. Using molecular biology experiments and polymer simulations they hypothesized that condensin has an additional bridging induced phase separation (BIPS) activity that is required for correct chromosome folding. In its absence, chromosomes are not fully compacted leading to chromosome instability.
I will collaborate closely with polymer physicists in Edinburgh to interpret experimental data and to understand how different condensin activities are necessary for chromosome folding. Together, we expect to provide a new model of condensin molecular functions based on experiments in vivo analyzed together with simulations of mitotic chromosomes. Deviations between simulations and experiments will be used to identify gaps in our knowledge leading to new hypothesis generation.
My aim is to investigate how different condensin activities (BIPS vs LE) regulate mitotic chromosome folding. To achieve this I have the following objectives:
(i) Use an in silico model of condensin-mediated chromatin folding with diverse levels of LE and BIPS to develop models of chromosome folding and generate testable hypotheses and predictions.
(ii) In human cells replace endogenous condensin components with already identified separation of function mutants to alter the balance between BIPS and LE activities and assess their role in chromosome folding.
(iii) Explore how different mutations affect condensin binding and clustering on mitotic chromosomes using super-resolution microscopy.
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 physical sciences optics microscopy super resolution microscopy
- natural sciences chemical sciences polymer sciences
- natural sciences biological sciences genetics mutation
- 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)
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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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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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(opens in new window) HORIZON-MSCA-2024-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
EH8 9YL Edinburgh
United Kingdom
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