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Specific Aims
AIM 1:
Illumination of human, animal model and bat virus-host networks involved in SARS-CoV replication, host tropism and host responses that govern disease outcome and human adaptation.
AIM 2:
Data integration, modeling, and hypothesis generation to identify molecular nodes and pathways that govern disease progression across clinical, in vivo, and ex vivo samples.
AIM 3:
Reiterative validation of host-pathogen interactions that impact virus replication, exacerbated host responses, host tropism and disease progression and severity in vivo and ex vivo.
Program Components
SYBIL Consists of Two Research Projects and Four Supporting Cores
PROJECT 1:
Identify early networks and signatures associated with mild and severe SARS-CoV-2 infections in vivo
Project 1, led by Rafael Medina and Michael Schotsaert, focuses on identifying early networks and signatures associated with varying severity of SARS-CoV-2 infections using a systems biology approach. This project utilizes retrospective and prospective studies in human cohorts from Chile and Spain, alongside animal models, to investigate factors influencing COVID-19 disease progression. The use of multi-OMICs technologies, including proteomics, transcriptomics, and immunophenotyping, aims to identify biomarkers of disease in both naïve individuals and those with pre-existing immunity. Experimental infections in different mouse models under controlled conditions help in understanding disease mechanisms and identifying potential therapeutic targets.
PROJECT 2:
Ex Vivo Analysis of Coronavirus Tropism, Adaptation, Replication, and Host Response
Under the leadership of Sumit Chanda and Adolfo García-Sastre, Project 2 employs ex vivo models and advanced OMICS techniques to analyze molecular signatures correlating with clinical disease outcomes and virus-host interactions. This project aims to elucidate networks and host genes involved in virus replication, host responses, and adaptation, using human and bat cell models. By integrating these findings with in vivo data from Project 1, the project seeks to identify critical regulators and potential therapeutic targets involved in disease outcomes.
CORE A: Administrative Core
Directed by Adolfo García-Sastre and co-directed by Sumit Chanda, Core A coordinates the SYBIL consortium’s operations. It establishes an organizational structure, oversees resource allocation, and facilitates communication among project teams. Additionally, Core A is responsible for training programs in systems biology, aiding in manuscript preparation, data sharing, and regulatory compliance.
CORE B: Technology Core
Nevan Krogan leads Core B, which provides cutting-edge OMICs technologies for analyzing samples from Project 1 and Project 2. This core combines expertise in genomics, proteomics, epigenomics, and viral mutagenesis to support the characterization of biological samples, aiding in the identification of disease biomarkers and therapeutic targets.
CORE C: Modeling Core
Directed by Rafick-Pierre Sékaly and co-directed by Slim Fourati, Core C processes and analyzes OMICs datasets from both projects, applying statistical and heuristic approaches to map these datasets onto biological networks. This core plays a crucial role in identifying disease progression patterns, host susceptibility differences, and potential therapeutic interventions.
CORE D: Data Management and Bioinformatics Core
Lars Pache heads Core D, which supports data management and bioinformatics needs across the SYBIL Center. The Core oversees the dissemination of data generated by the program and develops and maintains tools for analyzing, visualizing, and prioritizing systems-level data, ensuring that research is reproducible and accessible while facilitating collaboration and data exchange across the consortium.
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