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Aligning pigmentation and repair: a holistic approach for UV protection dynamics

Objective

The human body takes different measures in order to protect itself against the results of UV exposure and its accompanied hazards, such as skin cancer. Despite extensive studies regarding the molecular regulation of the two main UV protection mechanisms, namely, the DNA repair system and the pigmentation system, a comprehensive theory that simultaneously accounts for the two systems is still missing. Hence, the ground-breaking goal of this proposal is to elucidate, for the first time, the dynamic control used to schedule and synchronize the UV protection subsystems.
Since these two systems serve the same physiological purpose, but on different time scales (DNA repair takes minutes, while pigmentation lasts hours to days), I propose to take the novel approach of focusing on their timing as an opportunity to uncover their regulation. As a first step, we exposed human and mouse skin to UV and found that UV exposure at 48hr intervals resulted in higher skin pigmentation than did exposure at 24hr intervals, even after controlling for total UV dosage. Furthermore, we found that the expression level of the melanocyte central regulator, MITF, exhibits damped oscillatory behaviour during this 48hr interval. I therefore hypothesize that the dynamic behaviour of the central regulator dictates the UV–response timing of the two protection systems. In the proposed research, I will take a holistic approach and address this issue from three complementary perspectives: (1) transcriptional dynamics, (2) temporal effects on cellular output, and (3) DNA repair after UV. This will be achieved by utilizing and developing new experimental and analytical tools that will allow us to correlate the temporal behaviours of a wide set of molecular markers. Reaching our goals will provide a breakthrough in our understanding of skin protection from UV and the underlying mechanisms that control it. These findings may offer exciting new avenues for future skin cancer prevention.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

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.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-COG

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Host institution

TEL AVIV UNIVERSITY
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.

€ 1 971 875,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 971 875,00

Beneficiaries (1)

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