Νέα Θέματα Διπλωματικών Εργασιών στο Τμήμα Ιατρικής
The Immune Biology group of the School of Medicine is looking for 2 highly motivated final-year students for the following projects.
Project 1: The role of TE in cancer cell immune evasion.
Supervisors:
Assistant Prof. Achilleas Floudas, School of Medicine, achilleas.floudas@uoi.gr
Prof. Emeritus Theodoros Tavaras, School of Medicine
Cancer cells may evade the immune system by upregulating the expression of immune inhibitory molecules, including PDL-1 and PDL-2 and by producing immune-modulatory cytokines and metabolites.
-Among transposable elements (TE), LTR retrotransposons are genetic elements with the capacity to increase their genomic copy number and associate with genetic diseases and carcinogenesis. Activated retrotransposition events are accomplished via an RNA intermediate in the hypo-methylated cancer cell.
Despite their carcinogenic role, the potential effect of TE on the capacity of cancer cells to evade the immune system has not been elucidated.
In this study, previously published scRNAseq data of various cancers will be identified and analysed for the presence of LTR retrotransposons. Cancer cell clusters with higher LTR retrotransposon expression levels will be analysed for the expression of immune modulatory molecules followed by trajectory and pathway enrichment analysis. Cancer cell lines with or without activated LTR retrotransposons will be assessed by flow cytometric analysis following treatment with methylation-promoting drugs. The student will primarily receive training in scRNAseq data analysis, Flow cytometric analysis and cell culture. This is a primarily bioinformatics-based project with the opportunity for tissue culture of cancer cells and flow cytometric analysis.
Project 2: Deciphering the crosstalk between endothelial cells and macrophages in Inflammatory Arthritis.
Supervisors:
Assistant Prof. Achilleas Floudas, School of Medicine, achilleas.floudas@uoi.gr
Prof. Savvas Christoforidis, School of Medicine and Director of BRI.
Inflammatory Arthritis (IA) including Rheumatoid (RA) and Psoriatic (PsA) Arthritis are common chronic inflammatory autoimmune diseases affecting over 1% of the global population. The disease is highly progressive involving chronic inflammation of the joints, significant comorbidities and reduced quality of life. Macrophages play a vital dual role in forming a protective barrier (CX3CR1/MERTK) in the healthy synovium and by producing inflammatory cytokines and chemokines resulting in excessive autoimmune responses disrupting bone metabolism in patients with RA. Macrophages are highly plastic, and polarisation exists as a continuum with four known subtypes of M2 macrophages, namely M2a, M2b, M2c and M2d. Recent studies demonstrated that macrophages of patients with RA exhibit intermediate M1-M2 phenotype, highlighting their plasticity.
IA disease progression correlates with increased angiogenesis, however the cellular crosstalk between endothelial cells and immune cells remains poorly understood. In this study, we will utilize already acquired scRNA sequencing data of patients with RA and healthy control synovial tissue biopsies to build receptor-ligand networks and assess the potential communication between endothelial cells and synovial macrophages. Based on the initial bioinformatic analysis patient monocyte-derived macrophages will be cocultures with endothelial cell lines in the presence or absence of specific molecular pathway inhibitors.
This is a demanding project, the student will primarily receive training in scRNAseq data analysis, and based on progress, monocyte isolation and polarization, flow cytometric analysis, cell culture and other immune based assays.