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EASTBIO: Identifying mechanisms by which neuron-oligodendrocyte interactions regulate nervous system function and dysfunction using zebrafish as model.


   College of Medicine and Veterinary Medicine

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  Dr T Czopka, Prof L Erskine  Applications accepted all year round  Competition Funded PhD Project (Students Worldwide)

About the Project

Elucidating how our central nervous system (CNS) is formed, maintained, and how it can dynamically remodel is one of the major challenges to understand function and dysfunction of the CNS. Although it is clear that neurons need to make the right connections to tightly control which signals are exchanged between cells, we are still far from understanding how the fine tuning of neuronal connectivity is achieved. Over the past years, it has become clear that non-neuronal cells (i.e. glia) are crucial regulators of neural network development and plasticity. One major glial cell type are oligodendrocytes and their committed precursors, which make up about 10% of all CNS cells lifelong. Oligodendrocytes have well-established roles in making myelin. However, there are many more oligodendrocyte precursors throughout the brain than differentiate to myelin forming oligodendrocytes. How this abundant cell population affects CNS form and function is not clear.

Our research group aims to understand how oligodendrocytes communicate with surrounding neurons, and in turn affect structure and function of neurons and their axons. To do this, we use zebrafish as a model organism due its rapid development of a functional nervous system, while being accessible to researchers for high-resolution optical and functional imaging in intact living animals, as well as genetic and physiological manipulations of cell and network function. Our group uses this exhaustive array of experimental approaches to elucidate the role of oligodendrocytes for CNS formation, function, and repair.

 Previous work from our group has revealed novel roles of oligodendrocyte precursors in sculpting neural circuits in the visual system, and, consequently, for processing of visual information and visually guided behaviours. Recent unpublished data from RNA sequencing datasets revealed a range of candidate molecules that may mediate the effects, several of which link to neurodevelopmental disorders in humans, including autism, forms of epilepsy and mood disorders.

This PhD project aims to investigate the role of oligodendrocyte-encoded target genes with relevance to human diseases in regulating precise connectivity and synapse formation between neurons. Applied methods include using CRISPR/Cas-mediated gene editing, transgenesis, cutting-edge in vivo imaging approaches of intercellular interactions, as well as functional analysis of neural network function and animal behaviour.


Funding Notes

Information on How to Apply and to download application and reference forms can be found at http://www.eastscotbiodtp.ac.uk/how-apply-0
Reference request forms should be sent to two referees.
Completed application form, academic transcripts and reference request forms should should be submitted to [Email Address Removed] by 16 December 2021

References

1: Marisca, R., Hoche T, Agirre E, Hoodless LJ, Auer F, Barkey W, Castelo-Branco G, Czopka T. Functionally distinct subgroups of oligodendrocyte precursor cells integrate neural activity and execute myelin formation. Nature Neuroscience 23, 363–374 (2020).
2: Xiao, Y., Hoodless, L. J., Petrucco, L., Portugues, R. & Czopka, T. Oligodendrocyte Precursor Cells Sculpt the Visual System by Regulating Axonal Remodeling. bioRxiv 2021.03.11.434829 (2021) doi:10.1101/2021.03.11.434829. (preprint, currently under second review at Nature Neuroscience)
3: Nagy, C. et al. Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons. Nature Neuroscience 23, 771-781 (2020).
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