ImmunoMachines
Financiado
Unraveling the Supramolecular Architecture of Molecular Machineries in Adaptive...
To combat daily threats of pathogens and abnormal cells, the human organism features a sophisticated defense mechanism called the adaptive immune system. In broad terms, this intricate mechanism is triggered by specific peptide ep...
To combat daily threats of pathogens and abnormal cells, the human organism features a sophisticated defense mechanism called the adaptive immune system. In broad terms, this intricate mechanism is triggered by specific peptide epitopes presented on molecules of the major histocompatibility complex class I (MHC I), which are scanned by cytotoxic T cells. Intracellular transport, loading, and cell-surface recognition of antigenic peptides on MHC I are orchestrated by machineries, the peptide-loading complex (PLC) and the T cell receptor (TCR) complex. The PLC is composed of multiple subunits, including the antigen translocation unit TAP, the MHC I heterodimer, and several chaperones ensuring that only stable peptide-MHC I molecules are released to the cell surface for decoding by TCR complexes. Ligand binding and the supramolecular organization of TCR complexes are translated into phosphorylation of conserved tyrosine-containing cytosolic sequence motifs that initiate downstream signaling cascades. Based on their incredible efficiency and selectivity, we hypothesize that the biogenesis of MHC I is highly processive and coupled via allosteric networking, and that antigen processing and recognition machineries are compartmentalized by a defined supramolecular organization. However, despite their fundamental importance, these architectural details of the PLC and the TCR, as well as the dynamic networking that is included in the quality control of the endoplasmic reticulum (ER) and receptor signaling processes, remain enigmatic due to their inherent dynamics, low abundance, and complexity.This ambitious proposal will contribute to a long-awaited holistic understanding of the machineries that shape the vertebrate adaptive immunity. The expected findings from this project will be groundbreaking in understanding the hidden processes of epitope selection and reception in human disease.
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Duración del proyecto: 59 meses
Fecha Inicio: 2025-01-01
Fecha Fin: 2029-12-31
Fecha Fin: 2029-12-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2023-ADG:
ERC ADVANCED GRANTS
Cerrada
hace 1 año
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
JOHANN WOLFGANG GOETHEUNIVERSITAET FRANKFURT...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5