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Single-cell genomics to comprehensively understand healthy B-cell maturation and transformation to chronic lymphocytic leukemia

Project description

Mapping the path from immune cell to cancer

B-cells are highly dynamic lymphocytes in the immune system. When B-cells bind with an antigen, a chemical signal tells them to divide many times, resulting in an army of B-cells that ultimately produce thousands of antibodies in seconds. B-cells are also at the root of chronic lymphocytic leukaemia (CLL), the most common form of leukaemia in Western countries. CLL is characterised by abnormal growth and proliferation of neoplastic B-cells. EU-funded scientists are studying the maturation of thousands of healthy and diseased B-cells with the ambitious goal of characterising CLL molecular biology throughout the course of the disease process.

Objective

Unbiased analyses of the molecular make up of single cells are revolutionizing our understanding of cell differentiation and cancer. Over the last years, our groups have characterized the molecular features of normal B-cell subpopulations and of pools of leukemic cells from chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world. These analyses have revealed that CLL subtypes are related to different B-cell maturation stages, and that they can show a complex subclonal architecture. Such subclonality is dynamically modulated during the course of the disease, and has deep implications in CLL biology, clinical aggressiveness and treatment responses. In this scenario, BCLL@las aims at deciphering the origin and molecular anatomy of CLL during the entire life history of the disease by generating genetic, transcriptional and epigenetic maps of hundred-thousands of single cells across locations, time points and individuals. We plan to fulfill four major objectives: 1) To generate a comprehensive atlas of normal B-cell maturation, 2) To understand the initial steps of neoplastic transformation through the analysis of minute B-cell monoclonal proliferations in healthy individuals, 3) To decipher the cellular diversity and clonal architecture of CLL at diagnosis, and 4) To characterize the single-cell subclonal dynamics of CLL during disease evolution and treatment response. To reach these goals, BCLL@las gathers together four teams with complementary expertise in B-cell biology, clinics and pathology of CLL, genomics, transcriptomics, epigenomics, sequencing technologies, single-cell profiling and computational biology. This, together with the richness of the available CLL samples and the technical and analytical depth of BCLL@las shall lead to unprecedented insights into the origin and evolution of cancer in the precision medicine era.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-SyG - Synergy grant

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Call for proposal

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(opens in new window) ERC-2018-SyG

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Host institution

CONSORCIO PARA LA EXPLOTACION DEL CENTRO NACIONAL DE ANALISIS GENOMICO
Net EU contribution

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.

€ 2 297 376,31
Address
C BALDIRI 1 REIXAC 4
08028 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost

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.

€ 2 297 376,31

Beneficiaries (3)

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