Thesis topic proposal
Dynamics of small extracellurar vesicle-mediated communication in the tumor


Institute: University of Szeged
theoretical medicine
Doctoral School of Interdisciplinary Medicine

Thesis supervisor: Krisztina Buzás
Location of studies (in Hungarian): Department of Immunology, University of Szeged
Abbreviation of location of studies: Immun

Description of the research topic:

Current evidence suggests that small extracellular vesicles (sEVs) play key role in favoring cancer hallmark traits throughout the distinct stages of cancer progression. They can manipulate the local and systemic environment, including the immune system to evade anti-tumor response. In this project, we aim to describe the quantitative characteristics of the sEV-mediated communication network inside the heterogeneous tumor tissue and explore the chemotherapy-induced effects on that.
We will describe the sEV dynamics, i.e. secretion and internalization quantities across a cell culture panel of 8 normal and 16 tumor cells. We will explore correlations between the sEV dynamics and cell physiology, as well as aggressive cancer phenotype.
Using a novel, fast and cost-effective high-throughput method and 3D tumor models, we will investigate the crosstalk between tumor cells and normal stroma cells. We will describe the quantitative characteristics, heterogeneity and functional effects of the sEV network in tumors by using 3 different tumor cells and stroma cells, i.e. myeloid cells, fibroblasts, endothelial cells. Finally, we will also explore the chemotherapy-induced effects on the sEV dynamics.
We will introduce novel metrics, such as sEV dynamics constant, sEV activity value and sEV-index that ensure a comprehensive quantitative evaluation of sEV dynamics.
Through this study, we will solve a number of technical and theoretical issues, which is of interest to a significant part of the cancer and sEV research community ensuring publications in high rank journals. We will explore, whether:
− ratio of sEV release and uptake is equal in the eukaryotic cells,
− sEV dynamics depends on cell physiology,
− sEV activity is higher in tumor cells,
− tumorous reprogramming alter the sEV dynamics of stroma cells,
− adjacent cells and tissue structure influence the sEV dynamics in tumor,
− quantitative features of tumor sEV dynamics correlate with aggressiveness,
− quantitative features of tumor sEV dynamics reflect chemotherapy-induced responses of tumors.

Required language skills: english
Number of students who can be accepted: 1

Deadline for application: 2021-12-31

All rights reserved © 2007, Hungarian Doctoral Council. Doctoral Council registration number at commissioner for data protection: 02003/0001. Program version: 2.2358 ( 2017. X. 31. )