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Strengthening regional stem cells based research for advancement of multi modal innovative strategy for modelling neurodevelopmental disorders

Periodic Reporting for period 2 - STREAMLINE (Strengthening regional stem cells based research for advancement of multi modal innovative strategy for modelling neurodevelopmental disorders)

Período documentado: 2023-10-01 hasta 2025-06-30

Neurodevelopmental disorders (NDDs) encompass a broad and heterogeneous group of conditions resulting from disruptions in key neurodevelopmental processes. One of the primary challenges in studying NDDs lies in their extensive heterogeneity, both in phenotypic presentation and genetic architecture. These disorders are associated with a wide spectrum of neuropsychiatric and behavioral conditions, including anxiety, depression, autism spectrum disorder, intellectual disability, schizophrenia, and bipolar disorder. The genetic landscape of NDDs is highly complex, with over 1,000 genetic loci identified as contributing to increased risk. Identifying the genetic underpinnings of NDDs is essential not only for elucidating the molecular mechanisms driving their onset but also for facilitating accurate genetic counseling, guiding clinical management, and enabling timely medical intervention. NDDs are estimated to affect approximately 10 to 15% of all births, with prevalence rates increasing worldwide over the last years, bringing a large societal and financial burden in Europe and worldwide.
Patients with NDDs and mental health problems are geographically dispersed. In the Western Balkan Region research focused on NDDs is still facing limitations due to insufficient funding and gaps in technologies. To overcome these challenges, there is critical need to establish a high-capacity regional center with research infrastructure and practices aligned with those of EU institutions. The STREAMLINE project was launched to address this need by strengthening strategic networking and boosting the research and innovation potential of the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade (IMGGE). The aim was to develop IMGGE into a high capacity hub for research of NDDs in the Western Balkans, capable of full integration with top-tier research centers across Europe. This was achieved by twinning IMGGE with three top-class research institutions in Europe: Cardiff University (CU), University of Maastricht (UM) and Centre for Research and Technology Hellas (CERTH). As a key focus, the STREAMLINE project targets 22q11.2 Deletion Syndrome (22q11.2DS)—a condition caused by a microdeletion at the q11.2 region of chromosome 22. This syndrome is strongly associated with an elevated risk for various NDDs and represents one of the strongest known genetic risk factors for development of psychiatric illness and one of the highest known genetic risk for schizophrenia. These facts underscore the clinical relevance of 22q11.2DS as a model for investigating the genetic and neurobiological basis of NDDs.
STREAMLINE aimed to enhance the European critical mass for the NDD research by strengthening strategic networking and implementing novel methodologies crucial for advancing biomedical research on NDDs in Serbia and the wider Western Balkan region.
To reinforce research and innovation capacities, empower research staff, and establish long-lasting partnerships, IMGGE researchers received comprehensive training at STREAMLINE partner institutions in the following areas: cell reprogramming; generation and analysis of brain organoids; electrophysiological analysis of neurons; RNA sequencing; bioinformatics data analysis and development of a digitalized repository; and high-throughput cell-based assays for in vitro drug testing. All newly acquired methodologies have been successfully implemented at IMGGE, contributing significantly to its research capacity and expertise.
Major achievements of STREAMLINE Exploratory research project include: generation of an extensive collection of iPSCs (eight 22q11DS carriers and five non-carrier controls), including familial cases; successful employment of human iPSCs to identify cell biological phenotypes associated with the 22q11.2 microdeletion; and revealing that some cellular phenotypes are modifiable with pharmacological agents.
During the STREAMLINE, the research management capacities and administrative skills of IMGGE staff were strengthened through trainings covered the following components: preparation of proposals for EU funding calls; data protection and data sharing in biomedical research – focusing on legal frameworks and best practices; research project management; improving soft/professional skills of ESRs; ensuring data integrity; and preparation and management of EC-funded projects and applications. Exchange of best practices and experiences between IMGGE administrative staff and experts from UM enables IMGGE to establish Office for EU projects. To foster a collaborative ecosystem for research of NDDs in the Western Balkan region, STREAMLINE organized three spring schools, four symposia, two workshops, two Industry Open Days and four thematic workshops held at both national and international conferences. As a key outcome, the STREAMLINE HUB was launched, serving as a central platform for knowledge exchange and collaboration. As its integral component, the Expert Unit for Modelling NDDs was established at IMGGE.
STREAMLINE increases scientific knowledge about molecular mechanisms underlying NDDs, while also strengthening existing collaborations and establishing novel networks with researchers in the field. The project enhances cooperation between IMGGE and both Serbian and European partners by introducing cutting-edge methodologies and technologies. It also contributes to raising awareness and improving knowledge among healthcare providers regarding the genetic basis of NDDs. Furthermore, STREAMLINE establishes high-throughput, patient-specific drug testing platforms and facilitates the discovery of novel therapeutic targets, paving the way for more personalized and effective treatment strategies.
STREAMLINE is strategically designed to strengthen research and innovation capacities across all actors within the ecosystem of widening countries. By enhancing institutional excellence and fostering inclusive collaboration, the project increases the attractiveness of research careers, supports the retention of top talent, and boosts participation and leadership success in Horizon Europe initiatives.
STREAMLINE opens new research avenues, stimulates scientific creativity, and promotes the development of innovative approaches, while facilitating the mobility and professional growth of highly qualified researchers at IMGGE. Additionally, STREAMLINE advances the understanding of the molecular mechanisms underlying NDDs, thereby contributing to the development of more comprehensive diagnostic tools and therapeutic strategies, with long-term benefits for biomedical research and patient care.
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