Project description
Searching for the secrets hidden in the salamander’s genetic code
The loss of a limb has significant emotional and physical repercussions, and long-term impact on mobility and functioning, impacting individuals, their families and healthcare systems. Prosthetics, currently the best solution, come with their own challenges, including achieving a comfortable fit and a higher level of function. Regeneration of tissues, organs and organ systems is an active area of research. With the support of the Marie Skłodowska-Curie Actions programme, the TRANSPOLOTL project will profile the molecular mechanisms behind regeneration in salamanders, and the forces that drove their evolution. By identifying the changes that enabled this ability in salamanders, researchers hope to obtain insights relevant for regenerative medicine.
Objective
Salamanders are unique among tetrapods in that they possess the unrestricted capacity to fully regenerate limbs upon amputation. Why is this the only tetrapod taxon harbouring such a striking regenerative potential and how did it evolve are two of the biggest outstanding questions in regenerative research. Over the past two decades, transposable elements (TEs) have emerged as one of the major drivers of regulatory evolution, and it has yet to be explored whether their spectacular numbers in salamander genomes might provide a rationale for the emergence of such an extraordinary phenotype.
The first aim of this work will be to develop an ensemble of state-of-the-art, long-read sequencing compatible approaches to profile the highly-repetitive Axolotl genome and identify the full complement of cis-regulatory-elements (CREs) driving limb regeneration. Two methyltransferase-based technologies for the profiling of chromatin accessibility and histone modifications will be developed, applied to the regenerating limb at different timepoints and later used to identify TE-derived CREs.
This approach will not only shed light on the evolution and molecular mechanisms of limb regeneration but will also set the stage for the provocative possibility of using TEs to rewire mammalian gene-regulatory-networks (GRNs) and enable regeneration. While extensively employed in a wide range of genome engineering approaches, TEs have yet to be harnessed for the regulatory rewiring of GRNs in a directed evolution context. As part of the second aim of this work, I will establish an innovative, TE-based system for the regulatory rewiring of GRNs and employ it to screen for synthetic GRNs capable of reprogramming mouse fibroblasts into a limb-bud-like state, just as it occurs during regeneration in axolotl. Ultimately, by understanding the evolutionary mechanisms behind the emergence of limb regeneration, this work aims to provide an uncharted avenue for the development of regenerating mammals.
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 zoology
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences molecular biology
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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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.
1030 Wien
Austria
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