The overriding goal of this research program is to explore a new avenue in anticancer therapy by targeting the aberrant telomere maintenance processes in tumors. More specifically we will study possible modulators of telomeric protein/protein and DNA/protein interactions. CONSORTIUM We will achieve this goal of great relevance by bringing together an interdisciplinary high-level consortium of young investigators and building a collaborative environment for research, innovation and technology transfer. The research teams involved in this project encompass all of the requisite expertise to reach the proposed objectives and all of them have a demonstrated scientific leadership potential and independency and their research impact in terms of bibliometric parameters and recognitions (awards, grants, highlights) is impressive. The project will be coordinated by Francesco Ricci, a senior researcher at the University of Rome, Tor Vergata (RU_Ro2) who has experience in running similarly complex multidisciplinary projects and, in addition to public national and international research centres, has strong interactions with private companies. The project will foresee a strong collaboration and interaction between the involved groups. PROJECT OBJECTIVESThe project is focused on the development of a scientific and technological interdisciplinary platform able to simulate, measure and characterize interactions between proteins and DNA that are crucial in the telosome (or shelterin) telomeric complex, a key player for telomere protection (see later for more details). The project will allow to optimize and validate a range of novel different methods that could be transformatory for drug-screening applications. We will specifically apply these novel methods to find and characterize potential drug candidates able to “inhibit” the DNA/protein or protein/protein interactions. We will study the interaction between the proteins POT1 and TRF2 and specific telomeric DNA sequences. We will also focus our efforts in the study of the interaction between TRF2 and Apollo proteins which have been described to be very important for the telomere protection. Compounds able to inhibit these DNA/protein and protein/protein interactions could have a high potential as possible anti-cancer drugs as they would stop the uncontrolled replication of tumour cells. Increasing body of evidence in fact supports the idea that TRF2 and POT1 could be two key proteins for rapid apoptosis and/or senescence induction. Of note, no such drug candidates have ever been described for these targets to date.PROJECT'S IMPACT The goals of this project are highly ambitious and their achievement will have several benefits for the Italian and EU scientific excellence because of the high impact of this research in many aspects of the real life (health, cancer research, drug discovery).
The overriding goal of this research program is to explore a new avenue in anticancer therapy by targeting the aberrant telomere maintenance processes in tumors. More specifically, the project will develop a scientific and technological interdisciplinary platform that will be applied to the discovery of modulators of telomeric protein/protein and DNA/protein interactions. The specific targets of this project are the telomere/POT1 complex (DNA/protein interaction) and the TRF2/Apollo complex (protein/protein interaction) (Fig. 1). These interactions play a crucial role in telomere maintenance and protection and have huge implications for possible anti-cancer therapies.
|Data di inizio/fine effettiva||3/8/14 → 3/7/17|