The BIORISE project proposal aims at the establishment of a Bioinformatics ERA Chair at the Cyprus Institute of Neurology and Genetics (CING). CING is currently the most advanced organisation of Cyprus in the fields of Neurology, Genetics and Biomedical Sciences and its research infrastructure is strongly supported by European Structural and Investment Funds (ESIF) through the Cyprus Directorate General for European Programmes, Coordination and Development. Through BIORISE the CING will attract talented Bioinformaticians who will be integrated within its current organisational structure to satisfy urgent needs for Bioinformatics analyses. The CING has recently established a Translational Facility infrastructure, through the ESIF and Norway grants, that will be producing a substantial amount of genomics and proteomics data. Due to budget limitations and the current economic constraints of the country, recruitment of expert Bioinformaticians has not been possible. Therefore, establishment of the Bioinformatics ERA Chair through this funding opportunity will complement and upgrade the above investments, since it will enhance the timely analysis of data and contribute towards excellence in extraction of reliable and meaningful results from large biological datasets. Furthermore, the more effective analysis of genomic and proteomic data will increase the capacity and level of excellence of CING thus promoting participation in competitive research proposals at national and international levels. In addition, BIORISE will facilitate the introduction of a Bioinformatics course within the postgraduate programmes of the Cyprus School of Molecular Medicine thus promoting the education and training of young scientists in the cutting edge field of Bioinformatics. BIORISE will have an impact at organisational, national, European and international level resulting in new multidisciplinary networks and increasing mobility thus complementing and upgrading existing infrastructures.

Working memory (WM) capacity, the ability to temporarily store information in mind, is especially important to a broad range of intellectual abilities and for optimal performance in everyday life settings. However, WM capacity is highly limited, which necessitates determining the factors that optimize/constrain efficient WM storage and remembering. To this end, new behavioural and neuroimaging evidence indicates that WM performance is influenced by attentional control. However, precisely how attention influences WM is not yet fully understood. Here, the applicant proposes to test the hypothesis that specific alleles in two dopamine-related genes, DAT1 and COMT, are associated with neural correlates of attentional encoding and attentional maintenance in WM, which in turn influence WM capacity. To explore this hypothesis, a combination of cutting-edge experimental techniques will be employed. Specifically, the applicant will use molecular genetics, electroencephalography/event-related potentials (EEG/ERPs), and behavioural measures to delve into the biological pathways underpinning the interplay between attentional control and WM capacity. The expected results will map to specific genotypes, the phenotypes (cognition/behaviour) and endophenotypes (neural markers/oscillations) of attentional encoding and attentional maintenance, and their modulation of WM. Findings will shed new light on the underlying mechanisms constraining WM capacity and shift the knowledge frontier. The proposal negotiates a subject matter of considerable importance for European society because WM deficits are a predominant symptom in many mental and neurological diseases that fall within Europe’s health priorities. During the proposed project, the fellow will acquire scientific and complementary transferable skills based on her personalized career development plan and through intra-European mobility and advanced training will reach a position of professional maturity in research.

The EBV-MS Hop-on proposal sets the goal to enhance the capabilities of the EBV-MS consortium empowering it with systems bioinformatics and other holistic approaches including network-based analytics, multi-source data integration, incorporation of a-priori knowledge from existing data and computational drug repurposing. The objectives towards this goal can be listed as: (1) capitalize on the existing publicly available data to generate an integrated knowledgebase related to EBV, MS and EBV-MS relationship (2) generate a specific disease-to-disease network around EBV infection and MS including other viral infections, diseases in the spectrum of autoimmunity and neurodegeneration, (3) generate an integrative network-based bioinformatics approach that accounts for virus–genes–disease-related protein-protein interactions (PPIs), (4) perform bulk and personalized multi-source data integration on the wide spectrum of data that will be generated (genetics, omics, imaging, clinical and lifestyle) to generate AI-ready profiles, to generate patient-to-patient networks for subgroup identification and to feed computational drug repurposing pipelines, (5) exploit the EBV and Host genetics data to suggest/rank candidate drugs in a personalized manner after fine tuning the personalized computational drug repurposing pipelines with the models of MS Brain damage and of digital twins. The ambition of this hop-on proposal is to capitalise on the wealth of data that will be generated from the initial proposal, together with the existing publicly available data, to provide deeper insights into the targeting of Epstein-Barr virus infection for the treatment and prevention of multiple sclerosis using advanced bioinformatics approaches.

The main objectives of the initial BEHIND-MS project include the investigation of the immune system response to Epstein-Barr Virus (EBV) in the blood and brain and the detection of irregular immune activation due to EBV in people with Multiple Sclerosis (MS), the exploration of how EBV and the immune system can cause damage to the nerve cells in MS as well as the identification of MS onset and progression mechanisms and of new treatments. The BEHIND-MS Hop-on proposal aims to enhance the capabilities of the BEHIND-MS consortium with network-based integrative bioinformatics that will provide integrated roadmaps linking EBV-host imbalance to disease onset and progression in MS. The objectives towards this goal are: (1) to use scRNA-seq for the generation and analysis of cell-to-cell communication networks in blood and CSF in order to assess the interplay of the various immune cell types with the EBV-infected cells in MS and Healthy background, (2) to apply systems bioinformatics approaches to generate and analyze protein-protein interaction networks between virus proteins, host proteins and proteins related to MS pathology, (3) to incorporate the protein-protein interaction and gene regulation modules of the most significant players in the redox signalling pathways (4) to provide network-based pathway analysis and computational drug repurposing enabling better understanding of the underlying mechanisms and highlighting candidate repurposed drugs that may prevent MS onset or progression, (5) to build an integrative atlas representing a knowledge base with visual and interactive interface that will combine multi-level data measurements and a-priori knowledge regarding immune system, EBV infection and MS. The ambition of this hop-on proposal is to computationally generate high granularity roadmaps of cell-to-cell communication networks and protein-protein interaction networks that bridge EBV-host imbalance to disease onset and progression in multiple sclerosis.