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DABAT

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DNA sensing by AIM2 in activated B cells novel targets to improve allogeneic ha...

DNA sensing by AIM2 in activated B cells novel targets to improve allogeneic haematopoietic stem cell transplantation A recent paradigm shift is that B cells are pivotal in chronic graft-versus-host-disease (cGVHD), which is the most relevant cause of late non-relapse morbidity and mortality after allogeneic haematopoietic stem cell transplantati... ver más

30/09/2023

UBx

276K€

Presupuesto del proyecto: 276K€

Líder del proyecto

UNIVERSITE DE BORDEAUX No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2023-09-30

MSCA-IF-2019: Individual Fellowships

I+D

Cerrada hace 5 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

3 Participantes

UBx

275.62K€ | Lider

DUKE UNIVERSITY

N.D. | Participante

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Duración del proyecto: 42 meses Fecha Inicio: 2020-03-24
Fecha Fin: 2023-09-30

Líder del proyecto

UNIVERSITE DE BORDEAUX No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 276K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto A recent paradigm shift is that B cells are pivotal in chronic graft-versus-host-disease (cGVHD), which is the most relevant cause of late non-relapse morbidity and mortality after allogeneic haematopoietic stem cell transplantation. DABAT’s project hypothesis is that 1) DNA-sensing by AIM2 supports cGVHD pathological B cells through autocrine regulations and that 2) their DNase1L3 expression modulates DNA-sensing by AIM2. Doctor Sarantopoulos (Duke University, US, supervisor for the outgoing phase) recently performed a single cell RNA-Sequencing experiment showing that AIM2 is upregulated in cGVHD patient B cells. Upon DNA binding, the AIM2 protein induces AIM2 inflammasome formation that triggers pro-inflammatory cytokines secretion. The survival and function of pathological B cells in cGVHD seem to be based on similar mechanisms to those of marginal zone (MZ) B cells. Doctor Sisirak (Bordeaux University, France, supervisor for the incoming phase) showed that DNase1L3, a major enzyme regulating extracellular DNA exposure, could play a pivotal role in MZ B cells development. The researcher will conduct the DABAT project under the supervision of these two internationally recognized experts in cGVHD B cells and DNase1L3. He will study AIM2 and DNase1L3 in human B cells and in mouse models. This fellowship will provide him with advanced technical training in B cell studies, flow cytometry, transcriptomic, histopathology and animal handling. He could identify intrinsic molecular programs underpinning B cell pathobiology, so that agents targeting B cell can be developed to treat cGVHD. He will be the main spokesperson of the project to a large audience. This fellowship will be a crucial step to extend his knowledge, to develop his communication, management and leadership skills, and to enlarge his international professional network. He will then become a mature and independent researcher enriching EU expertise and networking in Immunology and Transplant Immunology.

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