Project description
Novel targets to improve allogeneic hematopoietic stem cell transplantation
B cells are pivotal in chronic graft-versus-host disease (cGVHD), which is the most common cause of late non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Recent single-cell RNA-sequencing studies demonstrated that AIM2 (absent in melanoma 2) is upregulated in cGVHD patient B cells. Upon DNA binding, the AIM2 protein induces AIM2 inflammasome formation and triggers pro-inflammatory cytokine secretion. Other related studies showed that the enzyme DNase1L3 regulating extracellular DNA exposure could play a pivotal role in B cell development. The EU-funded DABAT project will investigate AIM2 and DNase1L3 in human B cells and in mouse in vivo models. The research will address intrinsic molecular programmes underpinning B cell pathobiology and agents targeting B cells which can be developed for cGVHD treatment.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine immunology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine transplantation
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
33000 BORDEAUX
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.