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Determining the relationships between haematopoietic lineages using genetic barcoding

Objective

The immune system is made up of a series of white blood cell types, or leukocytes, that develop as a distinct lineage. They derive from haematopoietic stem cells (HSC), which divide and branch through several intermediate progenitor stages en route to leukocyte generation. Distortion of this process can lead to unchecked numbers as in leukaemia and lymphoma, or to deficiency of a particular immune cell. To influence the formation of distinct subsets of blood cells in the clinic, it is essential to first determine the branch points of progenitors and the degree of kinship between leukocyte progeny.

The identification of clonal progenitors has been used to determine these branch points. However, their characterisation requires single progenitor cell assays, which are technically demanding. Genetic barcoding is a novel technique that allows stable integration of a unique stretch of known nucleotides (the barcode) into the DNA of progenitors, such that they are maintained and can be screened in subsequent daughter progeny.

The barcodes, in effect, become the single cell tracking mechanism in this technique, thereby allowing a clonal assay but with the advantage of studying cells at a population level. This proposal aims to use genetic barcoding to assess i) the relationships of leukocytes to progenitors, ii) to determine how differentiation pathways alter upon stress, and iii) whether a true map of steady-state haematopoiesis can be mapped phylogenetically. Upon its successful application, it is envisaged that genetic barcoding can be used to address questions in development of many tissue types with potential application in stem cell therapies.

This is hoped to partly encourage the competitiveness and attractiveness of European science to international scientists and investors. This proposal also aims to foster crossover of interdisciplinary skills between the European and Australian research sectors with view to creating long-standing collaborations.

Call for proposal

FP6-2005-MOBILITY-7
See other projects for this call

Coordinator

VERENIGING HET NEDERLANDS KANKER INSTITUUT
Address
Plesmanlaan 121
Amsterdam
Netherlands