Georgina Xanthou’s Topic
TITLE: Delineation of the metabolic networks underlying activin-A-induced suppression on autoimmune central nervous system inflammation.
Scientific background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system (CNS) that affects approximately 2.5 million people worldwide. Pathogenic Th17 cells drive autoimmune inflammation and ensuing neurodegeneration in MS. Th17 pathogenicity is associated with changes in immunometabolic pathways. Hence, the identification of factors that modulate metabolic pathways associated with Th17 pathogenicity is essential for the suppression of MS. We have previously demonstrated that the protein activin-A suppresses Th17 pathogenic responses, associated with inhibition of proteins involved in certain metabolic pathways.
Our aim: is to decipher the effects of activin-A on metabolic changes in Th17 cells and how these affect their epigenome and transcriptional profile.
Mouse Th17 cells will be isolated and treated with activin-A or control (PBS).
(1) Metabolomic analyses will be performed to investigate changes in metabolites.
(2) ATAC-seq studies will investigate chromatin accessibility changes, followed by transcription factor motif enrichment analysis in open chromatic regions.
(3) ChIP-seq experiments will explore chromatin occupancy and gene regulation focusing on transcription factors involved in T cell metabolism and activin-A functions.
The aforementioned experimental approaches (which will be done by PhD and Post-doctoral fellows in Dr. Xanthou’s lab) will generate a large amount of data-sets.
Two (2) theses will focus on the study of the aforementioned data through comprehensive bioinformatics analyses (i.e. IPA, GO, KEGG pathways and other advanced statistical methods).
NAME & POSITION OF THE SUPERVISOR: Georgina Xanthou, Researcher C
LAB/GROUP, DEPARTMENT, INSTITUTION where the thesis will be executed:
Cellular Immunology Lab, Center for Basic Research, BRFAA