Periodic Reporting for period 1 - IDPro (Intrinsically disordered proteins in health and disease: mechanisms, molecular context and opportunities for drug discovery)
Période du rapport: 2023-09-01 au 2025-08-31
Nearly 40% of the human proteome does not fold into well-defined structures. Instead, these proteins, or parts of proteins, are intrinsically disordered, meaning they lack a fixed structure. These intrinsically disordered proteins (IDPs) play vital roles in cell communication, regulation, and adaptation. However, their flexibility also makes them notoriously difficult to study and to target with drugs. Understanding IDPs is one of the most exciting and challenging frontiers in modern molecular biology.
To push this frontier forward, the IDPro doctoral network brings together experts from nine leading research institutions and five partner organizations across seven European countries. Together, we are training eleven doctoral candidates (DCs) in the latest experimental and computational techniques to study IDPs. By combining fundamental research, interdisciplinary collaboration, and industry exposure, IDPro aims to transform our understanding of IDPs and turn these insights into new therapies for cancer, neurodegenerative diseases, and viral infections.
Scientific Objectives: From Molecular Mechanisms to Drug Discovery
IDPro’s research is organized into three main scientific work packages (WPs), each addressing a key question about IDPs.
1. Motifs and Mechanisms (WP1)
This research focuses on identifying the small linear motifs (SLiMs), short stretches of amino acids, that allow IDPs to bind to other proteins. Using advanced screening methods, we discover many new motifs and shown how these interactions can be regulated. We also explore how these motifs evolve and function in different species, shedding light on critical systems such as tumor suppression. Innovative techniques like single-molecule fluorescence and force spectroscopy are helping to visualize how these flexible molecules fold and bind in real time.
2. Larger Context (WP2)
IDRs don’t act alone. Instead, their behaviour depends heavily on the surrounding protein environment. Here, we are uncovering how interactions between structured and disordered regions determine function, regulation, and even disease.
3. Targeting and Cellular Networks (WP3)
One of IDPro’s boldest goals is to make IDPs druggable. We are developing and testing small inhibitors that can modulate IDP interactions within living cells. Promising advances are being made in this direction.
Training and Outreach
Beyond scientific discovery, IDPro is a training the nextgeneration research leaders. Eleven doctoral candidates have been recruited and are receiving comprehensive interdisciplinary training that combines advanced biophysical and computational methods with intersectoral exposure through secondments and workshops. The close interaction between academic and industrial beneficiaries ensures that trainees acquire both scientific depth and translational competence, making them highly competitive for future careers in academia, biotechnology and pharmaceutical research. In this way, IDPro directly strengthens European capacity in quantitative biosciences and contributes to the formation of a new generation of researchers fluent across disciplinary and sectoral boundaries.
Through a dedicated website, social media, and open-access publications, we share our findings with both the scientific community and the general public, emphasizing transparency and data sharing according to FAIR principles.
Looking Ahead
By combining fundamental discoveries with cutting-edge training and collaborative innovation, IDPro is preparing the next generation of scientists to turn the hidden world of disordered proteins into a source of future therapies and scientific breakthroughs.
To push this frontier forward, the IDPro doctoral network brings together experts from nine leading research institutions and five partner organizations across seven European countries. Together, we are training eleven doctoral candidates (DCs) in the latest experimental and computational techniques to study IDPs. By combining fundamental research, interdisciplinary collaboration, and industry exposure, IDPro aims to transform our understanding of IDPs and turn these insights into new therapies for cancer, neurodegenerative diseases, and viral infections.
Scientific Objectives: From Molecular Mechanisms to Drug Discovery
IDPro’s research is organized into three main scientific work packages (WPs), each addressing a key question about IDPs.
1. Motifs and Mechanisms (WP1)
This research focuses on identifying the small linear motifs (SLiMs), short stretches of amino acids, that allow IDPs to bind to other proteins. Using advanced screening methods, we discover many new motifs and shown how these interactions can be regulated. We also explore how these motifs evolve and function in different species, shedding light on critical systems such as tumor suppression. Innovative techniques like single-molecule fluorescence and force spectroscopy are helping to visualize how these flexible molecules fold and bind in real time.
2. Larger Context (WP2)
IDRs don’t act alone. Instead, their behaviour depends heavily on the surrounding protein environment. Here, we are uncovering how interactions between structured and disordered regions determine function, regulation, and even disease.
3. Targeting and Cellular Networks (WP3)
One of IDPro’s boldest goals is to make IDPs druggable. We are developing and testing small inhibitors that can modulate IDP interactions within living cells. Promising advances are being made in this direction.
Training and Outreach
Beyond scientific discovery, IDPro is a training the nextgeneration research leaders. Eleven doctoral candidates have been recruited and are receiving comprehensive interdisciplinary training that combines advanced biophysical and computational methods with intersectoral exposure through secondments and workshops. The close interaction between academic and industrial beneficiaries ensures that trainees acquire both scientific depth and translational competence, making them highly competitive for future careers in academia, biotechnology and pharmaceutical research. In this way, IDPro directly strengthens European capacity in quantitative biosciences and contributes to the formation of a new generation of researchers fluent across disciplinary and sectoral boundaries.
Through a dedicated website, social media, and open-access publications, we share our findings with both the scientific community and the general public, emphasizing transparency and data sharing according to FAIR principles.
Looking Ahead
By combining fundamental discoveries with cutting-edge training and collaborative innovation, IDPro is preparing the next generation of scientists to turn the hidden world of disordered proteins into a source of future therapies and scientific breakthroughs.
The IDPro doctoral network is making great progress in uncovering how intrinsically disordered proteins (IDPs) control vital processes in our cells. We have engaged 11 talented doctoral candidates that are getting excellent training, and have engaged in their respective research projects.
During the first reporting period, IDPro has made major scientific advances. Our doctoral candidates have discovered new binding motifs (SLiMs) that explain how IDPs interact with other proteins and regulate cellular communication. They also revealed how these interactions can be regulated, to potentially rewiring signalling networks. Other studies showed how chemical modifications, such as phosphorylation, control IDP activity. The results further clearly show that the context of IDRs matters for their functions. On the therapeutic front, IDPro scientists have developed new assays, molecular modulators, and disease models.
During the first reporting period, IDPro has made major scientific advances. Our doctoral candidates have discovered new binding motifs (SLiMs) that explain how IDPs interact with other proteins and regulate cellular communication. They also revealed how these interactions can be regulated, to potentially rewiring signalling networks. Other studies showed how chemical modifications, such as phosphorylation, control IDP activity. The results further clearly show that the context of IDRs matters for their functions. On the therapeutic front, IDPro scientists have developed new assays, molecular modulators, and disease models.
Together, the scientific achievements described above mark a shift from describing IDPs to predicting and controlling their behaviour. From an applied perspective, the results pave the way for targeting IDPs in living cells.
On a longer term, we are reinforcing Europe’s leadership in molecular medicine and training the next generation of scientists to translate IDP biology into real-world therapies.
On a longer term, we are reinforcing Europe’s leadership in molecular medicine and training the next generation of scientists to translate IDP biology into real-world therapies.