The importance of glial cells (the non-excitable component of the nervous system) for proper brain function and homeostasis is being increasingly recognized, but our understanding of the factors that regulate their production and survival is still incomplete. This project will use interdisciplinary approaches to investigate the role of Zeb1 in the generation and maintenance of glial cells in the brain.
We have recently shown that loss of Zeb1 in adult neural stem cells of the hippocampus increases their neuronal output at the expense of glial cells (Gupta et al. Cell Rep 2021). This suggests a role for Zeb1 beyond stem cell maintenance in determining the type of cells produced by neural precursors, enabling the generation of glial cells, or suppressing an alternative neuronal fate. Interestingly, mature astrocytes also express Zeb1, which could indicate that Zeb1 regulates other astrocyte-specific functions.
The goal of this project is to determine if Zeb1 is necessary for glial cell production during development and to investigate its roles in mature astrocytes. To accomplish this goal, Zeb1 will be selectively eliminated from a subset of neural progenitors at different embryonic timepoints, before or around the time when glial cells start to be produced. The impact of Zeb1 loss on glial cell production will be analyzed postnatally by assessing number, position and morphology of glial cells. Those experiments will be complemented by comparative RNA-Sequencing analysis of wild type and Zeb-deficient progenitors and astrocytes, because as a transcription factor, Zeb1 can activate or inhibit the expression of other genes, depending on which cofactors it associates with. This analysis will shed light on the networks of genes controlled by Zeb1 across different cell types. Finally, to investigate the role of Zeb1 in mature astrocytes, Zeb1 will be selectively eliminated from astrocytes postnatally using mouse genetics. Number, position and morphology of astrocytes in different brain regions will be analyzed and results compared to the effect of removing Zeb1 before the onset of gliogenesis.
This project is an interdisciplinary collaboration between three laboratories with experiences in developmental neuroscience (Dr Martinez-Garay), stem cell biology (Dr Siebzehnrubl) and computational bioinformatics (Dr Zhou). All three will jointly supervise the project. Their laboratories are closely located and with access to state-of-the-art equipment (e.g., confocal and light sheet microscopy).
*Please note that in their first year of the 4-year programme, DTP students will undertake taught units and rotation projects*
Eligibility Criteria
Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant research or non-academic experience.
In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification or experience is required (this includes a Physics A-level (grade B and above) or having undertaken units as part of your degree that have a significant mathematical component such as maths, statistics, bioinformatics. Applicants must ensure they highlight their Maths background within their application and to upload any supporting evidence.
To support PhD training opportunities, these studentships are only available to applicants that have not previously obtained or about to obtain a PhD degree (or equivalent).
If your first language is not English, you will need to meet the minimum English requirements for the programme (IELTS must be 6.5 overall and 6.5 in all sub-skills). Please note that the English Language requirement is stipulated by the University of Bristol, because of the first year taught elements, which is higher than is standard for Cardiff. We ask that the language requirements are met by 1st June at the latest, to allow adequate time to obtain any necessary documentation to allow you to study in the UK.
For more information about eligibility requirements, please visit: Eligibility – SWBiosciences Doctoral Training Partnership
How to Apply
To submit a formal application via Cardiff University’s online application service, click the 'Institution Website' button on this advert; in the ‘Apply’ box at the top-right of the page, select Qualification (Doctor of Philosophy), Mode of Study (Full Time) and Start Date (October 2022). This will take you to the application portal.
To apply for BBSRC SWBio studentships, candidates must submit the following:
Two references
Academic transcripts / degree certificate(s)
Personal statement. Please include supporting evidence for your Maths background.
Curriculum Vitae (CV)
English language certificates (where applicable)
NB: It is essential that students submit all the application elements required, as these will be needed for the shortlisting and interview processes.
In the research proposal section of the application, specify the project title and supervisors of the project. In the funding section, select “I will be applying for a scholarship/grant” and specify advertised funding from BBSRC SWBio DTP. If you are applying for more than one Cardiff University project, please note this in the research proposal section as the form only allows you to enter one title.
For more details on how to apply, visit the SWBio DTP website.
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