DeconstrucTolerance
Financiado
Deconstructing Intestinal Immune Tolerance
The intestinal tract is the main site of nutrient absorption and faces constant exposure to complex environmental stimuli. Intestinal barrier integrity and functionality are safeguarded by the intestinal immune system, which must...
The intestinal tract is the main site of nutrient absorption and faces constant exposure to complex environmental stimuli. Intestinal barrier integrity and functionality are safeguarded by the intestinal immune system, which must balance its pro- and anti-inflammatory activities to provide protection from pathogenic microorganisms while preventing unwanted reactivity to self-antigens, commensal microbes, and dietary components. The intestinal immune environment can be viewed as a multicellular network in which the identity and function of individual cells is intrinsically programmed by transcription factors (TFs) that regulate their gene expression. These cells in turn can respond to signals in their environment and impact the behavior of their neighbors, which over time drives changes in tissue physiology. Conventional genetic knockout approaches offer insufficient temporal resolution to dissect these regulatory layers.In this proposal, we will employ chemical genetic protein degradation using the auxin-inducible degron 2 (AID2) system to “deconstruct” the intestinal immune regulatory network. These studies will focus on the role of Foxp3+ regulatory T (Treg) cells, whose continuous immunosuppressive activity is required to prevent the onset of intestinal inflammation. In Aim 1, we will use newly generated mouse models to probe the direct gene regulatory functions of key TFs that define intestinal Treg cell subsets. In Aim 2, we will fluorescently label intestinal Treg cells and rapidly degrade the TFs that confer their suppressive activity to study their functionality in situ. Finally, in Aim 3, we will use a reversible mosaic protein degradation strategy to study how the signals that precede and promote intestinal Treg cell differentiation shape the developing intestinal immune system. Together, these studies will provide fundamentally new insights into the regulatory network underlying intestinal immune tolerance.
ver más
Duración del proyecto: 59 meses
Fecha Inicio: 2024-01-01
Fecha Fin: 2028-12-31
Fecha Fin: 2028-12-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-01-01
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2023-STG:
ERC STARTING GRANTS
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5