Projektbeschreibung
Antikörperanalyse zugunsten verbesserter Impfstoffe
Unser Immunsystem produziert eine Vielzahl einzigartiger Antikörper, von denen jeder in der Lage ist, bestimmte Antigene zu erkennen und an sie zu binden. Bei diesem Verfahren werden bestimmte Gensegmente genetisch neu gemischt, um verschiedene Antikörpersequenzen zu erzeugen, die mithilfe von Sequenzierung der nächsten Generation und bioinformatischen Analysen bestimmt werden können. Im Rahmen des vom Europäischen Forschungsrat finanzierten Projekts Antibodyomics wird ein solcher Ansatz zur Analyse des Antikörperrepertoires im Hochdurchsatzverfahren angewendet, um die Antikörperreaktionen nach einer Impfung zu analysieren. Die Forschenden werden sich mit verschiedenen Impfparametern und ihrer Rolle bei der Antikörperbildung befassen. Die Ergebnisse von Antibodyomics werden das Verständnis der Mechanismen von durch Impfstoffe vermittelten Antikörperreaktionen verbessern und den Weg für bessere Impfstoffe und Diagnostika ebnen.
Ziel
Vaccines and immunodiagnostics have been vital for public health and medicine, however a quantitative molecular understanding of vaccine-induced antibody responses is lacking. Antibody research is currently going through a big-data driven revolution, largely due to progress in next-generation sequencing (NGS) and bioinformatic analysis of antibody repertoires. A main advantage of high-throughput antibody repertoire analysis is that it provides a wealth of quantitative information not possible with other classical methods of antibody analysis (i.e. serum titers); this information includes: clonal distribution and diversity, somatic hypermutation patterns, and lineage tracing. In preliminary work my group has established standardized methods for antibody repertoire NGS, including an experimental-bioinformatic pipeline for error and bias correction that enables highly accurate repertoire sequencing and analysis. The overall goal of this proposal will be to apply high-throughput antibody repertoire analysis for quantitative vaccine profiling and discovery of next-generation immunodiagnostics. Using mouse subunit vaccination as our model system, we will answer for the first time, a fundamental biological question within the context of antibody responses - what is the link between genotype (antibody repertoire) and phenotype (serum antibodies)? We will expand upon this approach for improved rational vaccine design by quantitatively determining the impact of a comprehensive set of subunit vaccination parameters on complete antibody landscapes. Finally, we will develop advanced bioinformatic methods to discover immunodiagnostics based on antibody repertoire sequences. In summary, this proposal lays the foundation for fundamentally new approaches in the quantitative analysis of antibody responses, which long-term will promote the development of next-generation vaccines and immunodiagnostics.
Wissenschaftliches Gebiet
- medical and health scienceshealth sciencespublic health
- medical and health sciencesbasic medicineimmunologyimmunisation
- social sciencespolitical sciencespolitical transitionsrevolutions
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- natural sciencescomputer and information sciencesartificial intelligencemachine learningdeep learning
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-STG - Starting GrantGastgebende Einrichtung
8092 Zuerich
Schweiz