Thesis supervisor: László Nagy
Location of studies (in Hungarian): University of Debrecen Abbreviation of location of studies: DEÁOK
Description of the research topic:
Macrophages are heterogeneous immune cell populations with a remarkable diversity of functions and activation states in different anatomic locations. Their diverse phenotype is the result of a complex interplay between tissue micro-environmental signals and a hardwired differentiation program that determines macrophage identity and fulfills organ-specific and systemic trophic functions. However our knowledge is limited regarding the development of macrophage subtype specification and functional diversity. Our preliminary results laboratory pinpoint that the heme-regulated transcription factor, BACH1 is an important regulator in macrophages. It is found to bind extensively to chromatin sites and largely to co-localize with the master regulators PU.1 and CEBP/a. We found that existing BACH1 deficient mouse model likely underestimates BACH1’s function as it is a hypomorph mutant and not a KO.. We propose that BACH1 with its capacity to directly bind metabolites and sense the tissue micro-environment acts as a signal integrator sensing different tissue stimuli and shape transcriptional programs in macrophage subtypes. We will use new genetic tools coupled with transcriptomic and chromatin assays to readdress and dissect the contribution of BACH1 to macrophage specification in vivo. Our proposed experimental plan aims 1) to place BACH1 as part of the core macrophage master regulator complexes regulating macrophage identity/function, 2) to reveal BACH1- dependent homeostatic and inflammatory transcriptional programs in resident and inflammatory macrophages during muscle injury and 3) identify downstream effector molecules and macrophage-tissue crosstalk loops.
Number of students who can be accepted: 1
Deadline for application: 2018-05-15
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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