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Role of dynamic JNK signalling in balancing cell removal and renewal in a stressed epithelium

Project description

JNK signalling in the apoptosis and proliferation responses in stressed tissue

Tissue homeostasis requires maintenance of cell numbers, particularly in situations where additional proliferation is needed to compensate for cell loss. The c-Jun N-terminal kinase (JNK) belongs to the mitogen-activated protein kinase family, is responsive to stress stimuli and is a strong candidate for mediating both apoptosis and proliferation responses. Funded by the Marie Skłodowska-Curie Actions programme, the JNK_Life.Death project will elucidate the regulatory mechanisms of these two responses and the proliferative pathways activated by JNK using the Drosophila model, in which ribosomal protein deficiency causes extensive apoptosis compensated by extra proliferation. The objective is to uncover the transcriptional programmes that correlate with apoptosis and proliferation, identify the proteins involved and investigate their spatiotemporal activity upon JNK activation.

Objective

Tissue homeostasis requires a tight maintenance of cell number. Little is known about how tissue size and cell numbers are maintained in stress situations, when additional proliferation is needed to compensate for cell loss. I propose to study the homeostatic response to stress in a tissue (Drosophila wing primordia) in which Ribosomal Proteins-deficiency causes extensive apoptosis compensated by extra proliferation. How are these two responses balanced to ensure the emergence of a normal adult organism? JNK signalling is a strong candidate to mediate both apoptosis and proliferation responses. I propose to decipher the regulatory events that control this two-faced response, and to identify the proliferative pathways activated by JNK. Using the latest tools of genome engineering and live imaging, I aim at unravelling the spatio-temporal dynamics of JNK signalling and the downstream activation of cell death or division. Next, I will use a candidate gene and an unbiased approaches to uncover the transcriptional programs that correlate with apoptosis and proliferation. Lastly, I will verify the relevance of the identified candidates and investigate their spatial-temporal activity upon JNK activation. The results will be key to reaching the next stage of understanding the role of JNK in orchestrating the concerted replacement of lost cells that ultimately results in functional epithelia. Uncovering this logic in a relatively simple epithelium will hopefully guide further studies in more complex tissues of direct biomedical relevance.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

THE FRANCIS CRICK INSTITUTE LIMITED
Net EU contribution

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.

€ 212 933,76
Address
1 MIDLAND ROAD
NW1 1AT London
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Research Organisations
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Total cost

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€ 212 933,76
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