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

Periodic Reporting for period 1 - PhasAGE (Excellence Hub on Phase Transitions in Aging and Age-Related Disorders)

Reporting period: 2021-01-01 to 2022-03-31

The elderly population in Europe is in rapid expansion, raising a pressing concern about the increase of seriously 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. PhasAGE expects to create a European excellence hub at IBMC, while raising the research and teaching profile of all Partners’ staff. PhasAGE aims to foster the implementation of novel tools to study phase separation, while contributing towards responsible science communication and outreach activities with societal impact.

PhasAGE goal is to establish IBMC as an excellence hub in research and training on biomolecular phase transitions in age-related diseases, achieved through a joint training programme and exchange of best practices across disciplines, coupled with Think-Tanks to outline future R&I priorities on this topic. PhasAGE activities are structured around the Specific Scientific and Technological Objectives listed below:

-Enhance the impact and quality of research and training at IBMC on analysis of protein phase separation and aggregation in age-related human pathologies;
-Create a European excellence hub 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 at IBMC, UAB, VIB and UniPD;
-Increase the competitive edge of IBMC and enlarge networks at the national and international level;
-Contribute towards responsible communication of science and enhance scientific literacy.
PhasAGE project is focused on enhancing the knowledge and training of researchers in the field of biomolecular phase separation. Towards these aims, the PhasAGE project was launched in 2021 and included a scientific session during the Kick-off meeting (KOM), showcasing cutting-edge research from leading scientists in the field of protein aggregation and biomolecular phase separation. These first seminars were complemented with Expert Seminars with researchers from PhasAGE, and included Q&A sessions to stimulate the exchange of scientific expertise between consortium members and early stage researchers. The online PhasAGE I international conference (https://phasage.eu/phasage-conference-1/) further promoted the project’s scientific visibility. A symposium on protein aggregation and phase separation was organized at the Portuguese Neuroscience Society Meeting, constituting the first in-person event of the PhasAGE project.

Training of young researchers on biomolecular phase separation is a fundamental ambition of the PhasAGE consortium. Therefore, PhasAGE organized the training school 1 ”Computational Methods to Study Protein Phase Separation” a hands-on online course that provided participants with the knowledge of biomolecular phase separation and the expertise to use bioinformatic tools to study protein aggregation and phase separation (https://phasage.eu/training-school-1/). A portfolio with lectures and protocols, specifically developed for this training school was prepared and is publicly available in Zenodo (https://zenodo.org/communities/phasage). Part of the resources collected in this portfolio, are being conveyed in lectures for Ph.D MSc. and BSc. students from the host institution and from the University of Porto. The interest in the PhasAGE research topics at IBMC is high and resulted in the inclusion of 6 new PIs in the PhasAGE team of the coordinating institute.

To enhance the professional skills of early stage researchers, PhasAGE created a support programme including workshops focused on career development skills and alternative career opportunities (https://phasage.eu/career-development/). PhasAGE is also contributing to improve the R&I management expertise of the host institution staff through ongoing training, mentoring and benchmarking actions with consortium partners. Project outreach involved several activities with local high schools, and dissemination occurs through the project website and Twitter account.

The PhasAGE project has stimulated scientific collaboration among the partners, which resulted in several peer-reviewed publications (Nucleic Acids Res (doi: 10.1093/nar/gkab108) and Front Mol Biosci (doi: 10.3389/fmolb.2022.882160)).
PhasAGE project is actively contributing towards upgrading the impact of research and training at IBMC and consortium members, through the organization and implementation of training actions (training schools) scientific exchange and debate (Expert seminar series and conferences). PhasAGE has engaged enthusiastic early stage researchers, attracting them to the field of biomolecular condensates, and has supported and stimulated their career development skills.

The scientific and societal impact of PhasAGE was partly limited by the difficulties to organize the planned staff-exchanges and on-site activities in 2021/2022. In-person meetings are critical to reach the public, engage the patients’ associations, and promote new scientific collaborations. However, shifting the PhasAGE scientific meetings and seminars to the virtual mode allowed the inclusion of top-level speakers, and enhanced the number of participants, not only from different European countries but also from overseas. Virtual meetings were an unforeseen opportunity to foster the visibility of the PhasAGE project, IBMC, the partner institutions, and all its researchers. We anticipate that this visibility is long lasting, and will enhance the participation of early career researchers as well as scientists from academia and industry in future PhasAGE events.

We expect that the in-person events and staff exchanges planned for 2022/2033, will boost the scientific outcomes of the PhasAGE project and contribute to the implementation of optimized procedures to study phase separation, which will increase the competitive edge of IBMC and consortium members. In the long-term this knowledge will be critical to explore all opportunities to deter age-related diseases linked with aberrant phase separation, ultimately leading to improved health and well-being of European citizens.

PhasAGE outreach activities targeting the lay public and high-school students were extremely successful in enhancing awareness about the relevance of structure and disorder for protein function and disease. Teaching materials generated in the scope of these activities, easily transferable and adaptable to different audiences, will contribute to enhance the knowledge about the molecular mechanism underlying human disorders.

The PhasAGE project is raising the profile of Research and Innovation staff at IBMC through the organization of benchmarking activities with consortium members. A complementary mentorship program to exchange R&I expertise, is increasing the visibility of the PhasAGE institutions.
Analysis of LLPS behaviour of target proteins at IBMC (Credits to Sára Varga)