gutTEimpact | Illuminating the role of selfish genetic elements in somatic tissue homeostasis and aging

Summary
Life-long tissue homeostasis requires sustained function of differentiated cell types as well as progenitor cells, which ensure tissue self-renewal. Little is known about the role that non-genic repetitive DNA sequences play in the maintenance of cellular homeostasis in divers somatic tissues in vivo.
Transposable elements (TEs) are omnipresent, highly repetitive DNA sequences that mobilize and propagate within host genomes. Though previously thought to be fully repressed in the soma, TEs can be actively transcribed and, at least to some extent, mobile in certain somatic tissues. Indeed, somatic TE activity was proposed to contribute to normal development, aging, and pathologic conditions, such as cancer or neurodegeneration, underscoring the potential bearing that these selfish genetic elements could have in the soma. Nevertheless, the dynamics of activity and tissue-specific regulation of TE sequences are poorly understood, as is the impact of TE activity on different somatic cell-types and tissues.
We have recently uncovered that prevalent, tissue-specific TE mobility occurs in the Drosophila intestine and can lead to gene inactivation and tumor formation. Here, using this powerful and genetically amenable in vivo model system, I aim to combine genomic techniques with developmental and cell biology approaches to address the intriguing interplay between TEs and somatic tissue function in vivo. I will ask: 1- How TE activity differs between diverse cell types and how it changes in a tissue under normal or pathological conditions, as well as during aging? 2- What processes control TE activity in somatic cells in vivo?; and 3- What are the direct consequences of TE transcriptional activity and mobility on somatic cell function, and the long-term impacts at a tissue and organism level?
Ultimately the proposed research program will shed new lights on the importance of mobile DNA sequences in the maintenance of lifelong tissue homeostasis in vivo.
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Web resources: https://cordis.europa.eu/project/id/101078070
Start date: 01-05-2023
End date: 30-04-2028
Total budget - Public funding: 1 498 420,00 Euro - 1 498 420,00 Euro
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Original description

Life-long tissue homeostasis requires sustained function of differentiated cell types as well as progenitor cells, which ensure tissue self-renewal. Little is known about the role that non-genic repetitive DNA sequences play in the maintenance of cellular homeostasis in divers somatic tissues in vivo.
Transposable elements (TEs) are omnipresent, highly repetitive DNA sequences that mobilize and propagate within host genomes. Though previously thought to be fully repressed in the soma, TEs can be actively transcribed and, at least to some extent, mobile in certain somatic tissues. Indeed, somatic TE activity was proposed to contribute to normal development, aging, and pathologic conditions, such as cancer or neurodegeneration, underscoring the potential bearing that these selfish genetic elements could have in the soma. Nevertheless, the dynamics of activity and tissue-specific regulation of TE sequences are poorly understood, as is the impact of TE activity on different somatic cell-types and tissues.
We have recently uncovered that prevalent, tissue-specific TE mobility occurs in the Drosophila intestine and can lead to gene inactivation and tumor formation. Here, using this powerful and genetically amenable in vivo model system, I aim to combine genomic techniques with developmental and cell biology approaches to address the intriguing interplay between TEs and somatic tissue function in vivo. I will ask: 1- How TE activity differs between diverse cell types and how it changes in a tissue under normal or pathological conditions, as well as during aging? 2- What processes control TE activity in somatic cells in vivo?; and 3- What are the direct consequences of TE transcriptional activity and mobility on somatic cell function, and the long-term impacts at a tissue and organism level?
Ultimately the proposed research program will shed new lights on the importance of mobile DNA sequences in the maintenance of lifelong tissue homeostasis in vivo.

Status

SIGNED

Call topic

ERC-2022-STG

Update Date

31-07-2023
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2022-STG ERC STARTING GRANTS
HORIZON.1.1.1 Frontier science
ERC-2022-STG ERC STARTING GRANTS