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Neural Network Development Group

Development of neural networks & reactive oxygen species signalling in the nervous system

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Our goal is to understand the mechanisms that underlie the development of neural circuits and the emergence of coordinated function. We use the embryonic nervous system of Drosophila as a model, focussing on the development of the motor network that generates the simple crawling movements of the Drosophila larva.

Drosophila has been extremely influential for understanding mechanisms of neurogenesis and axon guidance, which have been highly conserved from flies to humans. Drosophila brings many advantages to this kind of analysis. The first is that we can work with identified neurons to which we can return again and again, as they develop and in experiments. The second is that by using targeted genetic constructs we can access specific cells in the developing network for experimentation and analysis. This is particularly important in the context of emerging function because it gives us an unparalleled ability to manipulate the excitability and synaptic connections of individual cells or cell classes. The third point is that we can use genetic methods to identify the molecular mechanisms that regulate structure, excitability and connectivity in the final stages of circuit assembly. Fourth, through serial section Transmission Electron Micoscopy volumes we now have access to the entire circuitry at synaptic resolution thanks to ground breaking work of Albert Cardona, Marta Zlatic and collaborators at HHMI Janelia Research Campus. This has already enabled many discoveries of unexpected connectivity motifs. 

More medically relevant, in collaboration with Sean Sweeney and Sangeeta Chawla at the University of York, we have begun exploring how oxidative stress, a hallmark of a ageing and neurodegenerative conditions, affects synaptic terminal growth, both in Drosophila and in vertebrate neurons. Here, we are discovering a different face of reactive oxygen species, namely as metabolic signals that inform neurons of their activity levels and regulate adaptive structural adjustments via highly conserved redox sensors and downstream signalling pathways. 

 

Ongoing Projects 

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Positions

Our research is supported by a variety of funding agencies, including The BBSRC, The Wellcome Trust, The Sir Isaac Newton Trust with previous support from The Royal Society, The Gates Cambridge Trust, The Katsia Foundation, Fondation Fyssen, and a Henslow Research Fellowship. 

If you are interested in joining our group, please e-mail Matthias Landgraf to discuss research projects and positions/lab space. We have been successful in obtaining support for promising scientists and are happy to help.

Collaborators

Richard Baines (Faculty of Life Sciences, University of Manchester)

Raymond Budjoso (Department of Veterinary Medicine, University of Cambridge)

Albert Cardona (HHMI Janelia Farm Research Campus)

Jan Felix Evers (Centre for Organismal Studies Heidelberg, Ruprecht-Karls- Universität, 69120 Heidelberg, Germany)

Lee Fradkin (Department of Molecular Cell Biology, Leiden University Medical Center)

Don van Meyel (Centre for Research in Neuroscience, McGill University)

Steve Stowers (Montana State University)

Sean Sweeney (Department of Zoology, University of York)

Gerd Technau (Institut für Genetik, Johannes Gutenberg Universität Mainz)

Davie van Vactor (Department of Cell Biology, Harvard Medical School)

Benjamin White (National Institute of Mental Health, NIH)

Marta Zlatic (HHMI Janelia Farm Research Campus)