Direkt zum Inhalt springen
login.png Login    |
de | en
MyTUM-Portal
Technical University of Munich

Technical University of Munich

Sitemap > Bulletin Board > Diplomarbeiten, Bachelor- und Masterarbeiten > Master thesis project: Alternative RNA splicing in mesenchymal stromal cells treated with exosomes from AML hematopoietic stem and progenitor cells
up   Back to  News Board    previous   Browse in News  next    

Master thesis project: Alternative RNA splicing in mesenchymal stromal cells treated with exosomes from AML hematopoietic stem and progenitor cells

23.05.2022, Diplomarbeiten, Bachelor- und Masterarbeiten

The Götze lab of the Technical University Munich works on the unraveling of the complex interaction between leukemic stem cells and the bone marrow microenvironment. We are currently offering a master thesis project in the exciting fields of cancer biology, stem cell biology and extracellular vesicles. The duration of the project is a minimum of 6 months and can preferably be preceded by a research internship of 2 months. Background knowledge and first practical experience of molecular and cellular biology is required. The position is available from the beginning of July and can, after proven suitability, be combined with a paid HiWi position (10h/week) from September. For more information or to apply, please contact the lead of the project, Dr Med Judith Hecker (judith.hecker@mri.tum.de)

Project Description:
Exosomes are a subtype of extracellular vesicles (EVs) that secreted from cells into the extracellular environment and are involved cell-cell communication, immune responses and tumor progression (1). The Götze lab has established a protocol to isolate and characterize extracellular vesicles from hematopoietic stem and progenitor cells (HSPC) from patients with acute myeloid leukemia (AML). Protein characterization of the cargo of these EVs with proteomics showed a dramatic increase of a high number of proteins involved in alternative RNA splicing compared to vesicles derived from healthy aged matched individuals.
Mesenchymal stromal cells (MSC) that reside in the bone marrow are integral parts of the bone marrow microenvironment (niche) and support hematopoiesis, the process that generates billions of new blood cells each day. MSC can differentiate into adipocytes and osteoblasts, a process that is altered in the bone marrow of AML patients and changes the bone marrow niche in favor of leukemic growth (2-4). Interestingly, alternative splicing has been shown to alter MSC differentiation, depending on which isoform of either osteo- or adipocyte genes is expressed (5).

Methodology:
The master student will analyze several characteristics of primary MSC after treatment with exosomes isolated from AML HSPC, with a particular focus on the differentiation capacity into adipocytes and osteoblasts. Alternative splicing of RNA will be analyzed by primer specific RT qPCR targeting genes that are involved in differentiation and proliferation. The student will be trained in bone marrow processing, standard cell isolation and culture techniques, exosome isolation and characterization, flow cytometry and RT qPCR.

References:

1. Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226-32.
2. Azadniv M, Myers JR, McMurray HR, Guo N, Rock P, Coppage ML, et al. Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support. Leukemia. 2020;34(2):391-403.
3. Zhang L, Zhao Q, Cang H, Wang Z, Hu X, Pan R, et al. Acute Myeloid Leukemia Cells Educate Mesenchymal Stromal Cells toward an Adipogenic Differentiation Propensity with Leukemia Promotion Capabilities. Advanced Science. 2022:2105811.
4. Battula VL, Le PM, Sun JC, Nguyen K, Yuan B, Zhou X, et al. AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth. JCI insight. 2017;2(13).
5. Park JW, Fu S, Huang B, Xu R-H. Alternative splicing in mesenchymal stem cell differentiation. Stem Cells. 2020;38(10):1229-40.

Kontakt: judith.hecker@mri.tum.de

More Information

https://med3.mri.tum.de/de/hematopoeitic-stem-cells-and-microenvironment