Cancer Research UK Edinburgh Centre

Analysing the impact of extracellular vesicles on microglia functions during brain tumour initiation stages

Supervisor: Dr Dirk Sieger

Dirk Sieger research image

High grade gliomas represent a complex and devastating disease. Microglia have been shown to infiltrate high grade gliomas and to actively promote their growth. However, little is known about the early stages of glioma growth and the interactions between tumour initiating cells and microglia. We have developed a novel zebrafish model to analyse brain tumour initiating stages and were able to show that microglia infiltrate pre-neoplastic lesions. Importantly, within the early tumour microenvironment, microglia are immediately reprogrammed and actively promote the proliferation of early tumour cells. We speculate that these changes are caused by direct crosstalk between the tumour initiating cells and microglia and that this is key for the development of the pro-tumoural activities of microglia 

We detected Extracellular vesicle (EV) release from brain tumour initiating cells and their uptake by microglia. We hypothesise that tumour initiating cells transfer miRNAs via EVs to microglia leading to alterations of gene expression within microglia.

This PhD project will address this hypothesis by i) live imaging and quantification of EV release and their uptake by microglia. ii) isolation of EVs followed by small RNA sequencing to get a detailed understanding of their miRNA content iii) directly testing the impact of identified miRNAs and their target genes on microglia in the tumour microenvironment.

Eventually, this project will provide a detailed understanding of EV mediated transfer of miRNAs to microglia during brain tumour initiation stages. This knowledge is of great importance for attempts in the field to restore microglial functions in the tumour microenvironment and to induce anti-tumoural activities in microglia.

Dirk Sieger Research Group