ESR6
Epigenomics of macrophage phenotypes and the contribution of transcription processes contributing to phenotype switch.
Noemí Caballero Sánchez is PhD Student at the Faculty of Medicine at the University of Debrecen. This doctorate program is associated with the European Training Network RENOIR which main goal is the study of muscle regeneration and aging.
She graduated in Biotechnology followed by a MSc in Molecular and Cellular Biology and Genetics. During her education, Noemí took part in several projects, in which she could gain practical experience in techniques and technologies commonly used in molecular and cellular biology, but also meant a great opportunity to reinforced and improved her knowledge in bioinformatics.
Currently, she is a member of the Nuclear Hormone Receptor Research Laboratory in the Department of Biochemistry and Molecular Biology of the University of Debrecen lead by László Nagy, who is the supervisor of the project. The major objective is the study of gene expression, epigenomics and immunophenotype changes that take place in macrophages along the muscle regeneration process.
University of Debrecen
Hungary
Partner Profile
University of Debrecen (UNIDEB)
University of Debrecen is one of the top three research universities in Hungary and a University of National Excellence.
The Faculty of Medicine has 23 clinical departments and 20 departments of basic sciences including Department of Biochemistry and Molecular Biology. Laszlo Nagy’s research group is part of RCMM (Research Centre for Molecular Medicine) research institute. The research groups of RCMM work in close collaboration with European and International partner institutions. In 2002, the research, training and networking activities of RCMM have been recognized by the European Commission and the “Centre of Excellence” title was awarded to the Centre. It hosts 28 research groups and 8 Core facilities and represents internationally recognized excellence in biomedical research. Its main research focus includes gene expression, nuclear receptors, clinical genomics, imaging, apoptosis, inflammation biology.
The ESR will be enrolled in the PhD program in Molecular and cellular immune biology at the Medical and Health Science Center at the University of Debrecen (https://www.edu.unideb.hu/)
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Topic
The progressive failure of muscle repair and an altered inflammatory response can lead to fibrosis that in turn can also negatively influence stem cells functionality.
Macrophages (MPs) subsets show mixed phenotypes that exhibit different functions mixing subsets that are beneficial for myogenesis and other subsets that are detrimental promoting fibrosis.
However, surface markers allowing to target precisely those subsets, as well as the major signaling pathways controling their behavior, are lacking.
We will study the epigenetic changes underlying the transition from inflammatory to repair MPs in both acute (CTX) and chronic (mdx) muscle injury on FACS-isolated Ly6Chi and Ly6Clow (and specific subsets identified according to the markers identified above) MP populations using single cell and bulk approaches at various time points at various time points. ATAC-seq experiments will be carried out to determine the open chromatin regions along with ChIP-seq of active (H4Ac and H3K27Ac) and repressive (H3K27Met3) histone marks.
We will built an epigenomic landscape dataset. Transcriptomic analyses will be also carried out from the same populations and changing gene sets and their genomic regulators will be determined using the bioinformatics pipelines developed at UNIDEB. The candidate transcription factors will be prioritized and their suitability as targets evaluated.
In a separate set of studies, candidate transcription factors will be analysed for their contribution of MPs gene expression and immunophenotype, including the heme-regulated transcription factor, BACH-1. Using BACH-1 KO mice we will carry on transcriptomic analyses on MPs and the involvement of the BACH-1 mediated pathways in disease progression will be identified by intersecting the datasets derived from wild type animals and DMD models.
Objectives
To isolate and characterize the chromatin structure of inflammatory Ly6Chi and repair Ly6Clow MPs from models of acute injury and DMD using ATAC-seq and ChIP-seq
To identify transcriptional regulatory molecules and pathways controlling the transition from inflammatory to repair MPs using RNA-Seq
To mechanistically dissect the role and contribution of select transcription pathways (BACH-1) using LOF studies in vivo to MPs assisted muscle repair in acute injury and in models of DMD
PHD Program
Molecular Cell and Immune Biology Faculty of Medicine
University of Debrecen
RENOIR
ESR
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