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A Novel Evolutionarily Conserved Cascade In The Immune System

Reference : PhD Angela GIANGRANDE

Offer publication : April 5, 2016

Cell differentiation requires factors that trigger specific transcriptional programs. Since the basic biological processes are conserved, these factors display similar functions during evolution. This makes it possible to use simple animals to tackle molecular cascades that are more difficult to study in higher organisms, due to genome duplication and to more complex body organization. The Drosophila Glide/Gcm transcription factor plays an instructive role in hematopoiesis. Fly blood cells provide the innate cellular and humoral immune response and constitute the professional macrophages upon infection or injury. Hematopoiesis relies on a very well conserved molecular
cascade. Given the role of Glide/Gcm, we speculated that the vertebrate orthologs play a role in the immune system and we analyzed the profile of expression of mGcm1 and mGcm2 in the major hematopoietic sites. Indeed, mGcm2 is expressed in myeloid and lymphoid lineages of the adult mouse. This has profound implications in both basic and medical science.

The candidate will work on the role of this type of transcription factor in the fly and in the mouse immune system. The candidate will proceed to analyze the function of mGcm2. The work will focus onto two cell types that express and imply mGcm2 in the immune response. We recently identified the direct targets of Glide/Gcm in flies. The candidate will also contribute to understanding the role this transcription factor in the immune response of mutant flies. These analyses will reveal the role of gcm genes in in evolution and will open novel perspectives in immunology, with a particular attention to diseases of the nervous system that are associated with defective immune response. We dispose of the KO mice and we have generated a conditional KO in the lab. A transgenic line expressing the GFP in microglia, the scavenger cells of the vertebrate nervous system, is also available and will be used to identify
and purify these cells in wild type and in KO mice. The analysis of the KO phenotype will be facilitated by the competences available at the Clinique de la Souris and will benefit from ongoing collaborations within and outside the IGBMC. The fly tools are also already available in the laboratory

- WISHED SKILLS : Knowledge and expertise in cell differentiation and immunity will be acquired. This is a multidisciplinary project that will also use imaging and molecular biology as well as bioinformatics.Basic knowledge in genetics, molecular biology and cell biology. Being familiar with mouse
biology will be a plus.

- EXPERTISES WHICH WILL BE ACQUIRED DURING THE TRAINING : Knowledge and expertise in cell differentiation and immunity will be acquired. This is a multidisciplinary project that will also use imaging and molecular biology as well as bioinformatics.

Your application

Application Deadline : Dec. 31, 2016

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