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Neuron-glia interactions during development and repair

Supervisor: Dr Matthias Landgraf

 

Project summary:

Glia are more numerous than nerve cells in our brains, yet their contributions to network development and function remain far from understood. Working with the Drosophila larva as an experimental model, we are studying the requirement of subsets of glia in mediating structural plasticity of dendrites and neuromuscular junctions during development. Furthermore we are exploring how these glial are recruited to facilitate neuronal plasticity and repair following injury.

We have identified reactive oxygen species (ROS) as a novel signal for neuron-glia communication, and determined that different ROS generators are active in distinct cell populations and subcellular localisations. We have developed an experimental paradigm for inducing neurodegeneration and identified suppressors of degeneration in a genetic screen.

Now we need to ask: How are ROS generators regulated with subcellular specificity? And how are ROS signals transmitted between cells? What are the molecular mechanisms by which neuron-glia interactions mediate changes in synaptic terminals during development and repair?

What the student will be doing:

In this project you will use state of the are genetic expression systems, live imaging and electrophysiology to characterise events at the neuron-glia interphase during development and following excitotoxic insults/injury. Biochemical screens have been designed to identify putative regulators of the ROS generating enzymes. We resolve synaptic sites using super-resolution imaging methods, such as expansion and STED microscopy.

References:

1.     Oswald MCW, Brooks PS, Zwart MF, Mukherjee A, West RJH, Morarach K, Sweeney ST and Landgraf M. (2017). Reactive Oxygen Species Regulate Activity-Dependent Neuronal Structural Plasticity.  Preprint  bioRxiv 081968.  DOI: dx.doi.org/10.1101/081968      PMCID: PMC5888200 

2.     Peco, E., Davla, S., Camp, D., Stacey, S., Landgraf, M., & van Meyel, D. (2016). Drosophila astrocytes cover specific territories of CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch. Development (Cambridge, England). http://doi.org/10.1242/dev.133165

3.     Stogsdill, J. A., & Eroglu, C. (2017). The interplay between neurons and glia in synapse development and plasticity. Current Opinion in Neurobiology, 42, 1–8. http://doi.org/10.1016/j.conb.2016.09.016

4.    Couton L., Mauss A.S., Yunusov T., Diegelmann S., Evers JF., Landgraf M. Development of connectivity in a motoneuronal network in Drosophila larvae. Curr Biol. 25:568-76 (2015).  doi: 10.1016/j.cub.2014.12.056.

5.     Oswald, M. C. W., Garnham, N., Sweeney, S. T., & Landgraf, M. (2018). Regulation of neuronal development and function by ROS. FEBS Letters. http://doi.org/10.1002/1873-3468.12972