Excellence Hub on Phase Transitions in Aging and Age-Related Disorders

Project Information

PhasAGE

Grant agreement ID: 952334

DOI

10.3030/952334

Project closed

EC signature date 2 July 2020

Start date 1 January 2021

End date 31 March 2024

Funded under

• Twinning of research institutions

Total cost

€ 899 741,25

EU contribution

€ 899 741,25

Coordinated by

INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC
Portugal

Periodic Reporting for period 2 - PhasAGE (Excellence Hub on Phase Transitions in Aging and Age-Related Disorders)

Reporting period: 2022-04-01 to 2024-03-31

Summary of the context and overall objectives of the project

The elderly population in Europe is in rapid expansion, raising concern about the increase of incapacitating age-related diseases. PhasAGE aims to strengthen the excellence, knowledge, and innovation potential of Instituto de Biologia Molecular e Cellular (IBMC) in biomolecular phase transitions in age-related diseases. By establishing a sustainable collaborative network between IBMC and the University of Padova (UniPD, IT), the Autonomous University of Barcelona (UAB, ES), and the Vlaams Instituut voor Biotechnologie (VIB, BE), PhasAGE aims to enhance the impact and quality of research and training at IBMC on computational and experimental analysis of protein phase separation, while contributing towards responsible science communication and outreach activities with societal impact. PhasAGE activities are structured around the following Specific Scientific and Technological Objectives:

-Enhance the impact and quality of research and training at IBMC;
-Create a European excellence center on phase transitions at IBMC and raise the research and teaching profile of all partners' staff (especially ESRs);
-Develop and implement novel tools and technologies;
-Increase the competitive edge of IBMC and enlarge networks at the national and international levels;
-Contribute towards responsible communication of science and enhance scientific literacy.

The PhasAGE project has advanced research and training in protein phase separation and aggregation in age-related diseases, establishing IBMC as a European excellence hub. Key achievements include the development of novel tools and software, which contribute to the understanding and treating age-related protein aggregation disorders. The publication of 42 open access articles, including 6 collaborative papers, underscores the project's scientific impact. PhasAGE organized five training schools, seminars, and workshops, enhancing the skills and career prospects of ESRs, and facilitating international collaborations to further strengthen the research community. PhasAGE dissemination and outreach efforts, including the organization of international conferences and engagement activities with patient associations, have raised awareness about the significance of protein phase separation research. This fostered responsible science communication and contributed to increasing scientific literacy. Overall, PhasAGE has successfully enhanced the research capacity, networking, and visibility of IBMC and its partners, establishing a robust European research ecosystem focused on biomolecular phase transitions in age-related diseases. The project's activities have not only advanced scientific knowledge but also had a positive impact on society and the ecosystem surrounding IBMC.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

PhasAGE aimed to establish IBMC as a leading center for research and training on biomolecular phase transitions in age-related diseases. This goal was pursued through several initiatives, including a pilot research program (WP1), extensive training and mentoring for researchers (WP2-3), and advancements in research and innovation practices (WP5). Dissemination and communication activities (WP4) were integral to the project, ensuring widespread impact and engagement, supported by efficient project management (WP6), and in strict adherence to defined ethics requirements (WP7). The main results obtained include:

1. Research. PhasAGE has contributed to the scientific understanding of protein phase separation. Software and tools were developed, including NAGPKin for analysis of protein phase separation kinetics, the SynPepDB database for peptides targeting toxic protein aggregation, the FuzDB database for fuzzy protein complexes, and the A3D database for structure-based aggregation prediction.
2. Training and Career Development. Expert seminars and staff exchange actions promoted international collaboration and interest in biophysics and computational science, while offering tailored training and mentoring to support the career development of ESRs and postdocs.
3. Dissemination, exploitation and outreach. In terms of dissemination and outreach, PhasAGE hosted three International Conferences and PhasAGE partners were invited to speak at several international conferences to disseminate research results, increasing the project's and consortium members' visibility. Active communication channels facilitated public outreach. We successfully bridged the gap between scientific research and community engagement, promoting a deeper understanding and appreciation of the project’s goals and achievements. The itinerant exhibition " A Rare Look" raised awareness about rare diseases and the importance of protein structural studies and fostered meaningful connections with diverse audiences, thereby amplifying the visibility and societal relevance of PhasAGE’s research initiatives.
4. Exploitation and Technology Transfer. Partner collaboration enhanced the knowledge of technology transfer opportunities. The filing of international patent applications exemplifies the project's successful exploitation of research outcomes, potentially leading to new treatments for age-related diseases.
5. To strengthen our research and innovation (R&I) capacitation, we implemented WP5 to enhance research capacity, networking, and visibility and expand our R&I management capacity. Benchmarking in R&I Management, and the organization of R&I Leap Forward Winter School contributed toward this aim. The digital platform "PhasAGE HUB" was established as a comprehensive resource for publications, software, and learning materials.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

PhasAGE has significantly advanced research on biomolecular phase transitions, particularly in the context of age-related diseases. By training a new generation of researchers, PhasAGE has strengthened the scientific community and contributed to societal understanding of age-related disorders. PhasAGE has made substantial progress beyond the current state of the art by developing standard protocols, innovative tools, and databases for a better understanding of LLPS, and strategies to counter aberrant biomolecular condensates, enhancing PhasAGE partners' research capacity and fostering an environment of continuous collaboration and innovation.

PhasAGE outputs are anticipated to lead to new therapeutic strategies for age-related diseases, thereby having a profound socio-economic impact. Additionally, the tailored training and career development programs for early-stage researchers will contribute to the creation of a highly skilled scientific workforce, furthering the project's long-term sustainability. PhasAGE’s public engagement efforts, have increased awareness and understanding of the importance of protein structural studies to understand and treat human diseases. These outreach initiatives have educated the public and emphasized the societal relevance of scientific research, fostering a community that is well-informed and actively involved.

PhasAGE has established fruitful interactions with several European consortia in related fields, including ML4NGP, TWIN2PIPSA, TWIN4PROMIS, and IDP2Biomed. These collaborations have strengthened the project's network and will ensure the maintenance and sustainability of PhasAGE’s goals and outcomes. By leveraging these partnerships, PhasAGE is well-positioned to continue its impactful research and training initiatives, fostering ongoing innovation and excellence in the study of biomolecular phase transitions.

Analysis of LLPS behaviour of target proteins at IBMC (Credits to S. Varga)

Analyis of the solution structure of a glutamine-repeat protein (Credits to J. Manso)