Wellcome Trust Featured PhD Programmes
Imperial College London Featured PhD Programmes
University of Edinburgh Featured PhD Programmes
Birkbeck, University of London Featured PhD Programmes
The Hong Kong Polytechnic University Featured PhD Programmes

Precision Medicine DTP - Analyzing network formation during brain tumour initiation


Project Description

Background

High grade brain tumours (HGBTs) represent a complex and devastating disease and are posing an unmet clinical need. These tumours resist multi-modal therapies and survival times are only 15 months on average. Microglia, the resident immune cells of the brain, are found in large quantities within HGBTS and are considered to actively promote the growth of these tumours. Recent data shows that HGBTs form functional networks which provide growth advantages and resistance to therapy (Osswald et al., 2015). These functional networks resemble many features of networks that are formed by neural progenitors during development, which has been discovered by the Uhlén laboratory (Malmersjö et al., 2013). Intriguingly, recent data from the Sieger laboratory suggest that functional networks might already be established during brain tumour initiation stages and that microglia play an active role in the establishment of these networks (Chia et al., 2019). Furthermore, pilot data suggests that direct cellular contacts between the microglia and brain tumour initiating cells might be crucial for network formation.

Aims

The aim of this project is to understand the mechanisms of network formation during brain tumour initiation stages and the role of microglia in this process. Here, established zebrafish HGBT models will be employed and in vivo live imaging of Ca2+ transients will be used to analyse network formation. Network dynamics and topology will be studied using statistical physics and concepts from graph theory to allow a direct comparison to previously described developmental and tumour networks. To understand the role of microglia in network formation, brain tumours will be induced in brains devoid of microglia and brains of p2ry12-/- microglia which show significantly reduced cellular interactions with brain tumour initiating cells. Finally, single cell sequencing of brain tumour initiating cells will be performed from wildtype brains, microglia null brains and p2ry12-/- brains to gain a detailed understanding of the transcriptional changes upon network formation and the role of microglia in this process.

Training Outcomes

This project will provide training on a variety of laboratory, quantitative, mathematical and bioinformatic skills. During the initial phase of the project training will be focused on the in vivo brain tumour model. This includes training on the animal model (zebrafish), state of the art molecular biology techniques and high-resolution live imaging. The second phase of the project will focus on quantification of the acquired Ca2+ imaging data and mathematical modelling of networks. During the final phase of the project training will focus on bioinformatic skills to analyze the quired single cell RNA sequencing data.

This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.

http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available from the link above.

For more information about Precision Medicine visit:
http://www.ed.ac.uk/usher/precision-medicine

Funding Notes

Start: September 2020

Qualifications criteria: Applicants applying for a MRC DTP in Precision Medicine studentship must have obtained, or will soon obtain, a first or upper-second class UK honours degree or equivalent non-UK qualification, in an appropriate science/technology area.
Residence criteria: The MRC DTP in Precision Medicine grant provides tuition fees and stipend of at least £15,009 (RCUK rate 2019/20) for UK and EU nationals that meet all required eligibility criteria.

Full eligibility details are available: View Website

Enquiries regarding programme:

References

1. Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J, et al. Brain tumour cells interconnect to a functional and resistant network. Nature. Nature Publishing Group; 2015 Dec 3;528(7580):93–8.

2. Malmersjö S, Rebellato P, Smedler E, Planert H, Kanatani S, Liste I, et al. Neural progenitors organize in small-world networks to promote cell proliferation. Proceedings of the National Academy of Sciences. 2013 Apr 16;110(16):E1524–32.

3. Chia K, Keatinge M, Mazzolini J, Sieger D. Brain tumours repurpose endogenous neuron to microglia signalling mechanisms to promote their own proliferation. Elife. 2019 Jul 17;8.

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully





FindAPhD. Copyright 2005-2019
All rights reserved.