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DNA helicases in genome maintenance: from molecular and cellular mechanisms to specific inhibitors as potential drugs

Objective

Helicases are ubiquitous enzymes, found in viruses, Bacteria, Archaea and eukaryotic cells. They act as motor proteins to separate or remodel DNA or RNA duplexes, using ATP as an energy source. Helicases play a key role in a variety of cellular processes, including DNA replication/repair/recombination, as well as RNA translation and transport. They are emerging as an important class of targets for antiviral, antibiotic and anti-cancer drugs. To date, several genetic and biochemical studies have revealed the molecular and physiological functions of DNA helicases. Moreover, protein three-dimension structural studies coupled with single molecule biophysical approaches have provided insights into structure-function relationships and reaction mechanisms of some key DNA helicases. With a consortium including experts with complementary competence and expertise in Physics, Chemistry, Biology and Clinical Oncology, and a strong commitment of companies involved in drug discovery or in the development of state-of-the-art biophysical instrumentation, we aim to: 1. obtain a detailed picture of the mechanism of action and the physiological role of a number of DNA helicases that are implicated in human diseases; 2. discover specific inhibitors of those enzymes, which can then be tested as novel therapeutic drugs, especially for cancers; 3. address the need for training next generation scientists with complementary approaches and diverse techniques by secondments in different laboratories of the consortium; 4. promote a culture of collaboration between academic and private sectors and provide young scientists with the necessary experience and skills to exploit the full potential of research findings; 5. provide early stage researchers with greater opportunities to access an increasingly competitive job market; 6. promote the values of Open Science and educate young scientists on the importance of a culture of openness, transparency, accessibility, integrity and reproducibility.
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Coordinator

CONSIGLIO NAZIONALE DELLE RICERCHE

Address

Piazzale Aldo Moro 7
00185 Roma

Italy

Activity type

Research Organisations

EU Contribution

€ 522 999,36

Participants (8)

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ELETTRA - SINCROTRONE TRIESTE SCPA

Italy

EU Contribution

€ 522 999,36

KOBENHAVNS UNIVERSITET

Denmark

EU Contribution

€ 595 044

STICHTING VU

Netherlands

EU Contribution

€ 265 619,88

THE UNIVERSITY OF SHEFFIELD

United Kingdom

EU Contribution

€ 303 172,56

UNIVERSITAETSKLINIKUM ESSEN

Germany

EU Contribution

€ 252 788,40

LEAD DISCOVERY CENTER GMBH

Germany

EU Contribution

€ 505 576,80

EDELRIS SAS

France

EU Contribution

€ 274 802,04

LUMICKS B.V.

Netherlands

EU Contribution

€ 265 619,88

Project information

Grant agreement ID: 859853

Status

Grant agreement signed

  • Start date

    1 October 2019

  • End date

    30 September 2023

Funded under:

H2020-EU.1.3.1.

  • Overall budget:

    € 3 508 622,28

  • EU contribution

    € 3 508 622,28

Coordinated by:

CONSIGLIO NAZIONALE DELLE RICERCHE

Italy