My lab uses zebrafish as a model to study myelination in the development central nervous system. The small size, optical transparency, relative simplicity, and rapid development of zebrafish embryos are properties that allow direct observation of entire developmental (or repair) events as they occur in live animals. We have developed a non-invasive transgenic method to induce demyelination in zebrafish and have also generated a suite of tools to visualise myelin and myelinated axons at high-resolution in live zebrafish, which allows us to observe cellular, sub-cellular and molecular behaviours during myelination, demyelination, and remyelination as they occur in a living animal.
Zebrafish are well established as a powerful system with which to identify new genes required for biological events. In a genetic screen carried out at Stanford University I identified new roles for genes with known involvement in myelination, established zebrafish models of human disease, and identified new genes required for myelination. Ongoing gene discovery screens at the Univeristy of Edinburgh will identify additional genes that regulate myelinated axon formation and function, particularly in the CNS.
Zebrafish have also become increasingly popular for drug discovery studies. Zebrafish embryos are small, aquatic, and available in very large numbers, which means that large-scale screens can be carried out in a cost-effective manner that is not possible using other animal models. This means that the effect of thousands of potential drug like compounds can be tested on whole animals at a very early stage of the drug development process. Importantly, zebrafish exhibit well-conserved responses to drugs approved for use in man, and new clinical trials based on work carried out in zebrafish are already in progress. We hope to identify compounds that can enhance the repair of myelinated axons in zebrafish, from which new therapies for humans can be developed.
Please see also: http://www.cnr.ed.ac.uk/Research/lyons.html
Snaidero N, Möbius W, Czopka T, Hekking LH, Mathisen C, Verkleij D, Goebbels S, Edgar J, Merkler D, Lyons DA, Nave KA, Simons M. Myelin Membrane Wrapping of CNS Axons by PI(3,4,5)P3-Dependent Polarized Growth at the Inner Tongue. Cell. (2014) 156(1-2):277-90.
Czopka T., Ffrench-Constant C., Lyons DA. (2013) Individual oligodendrocytes have only a few hours in which to generate new myelin sheaths in vivo. Dev. Cell , 25 (6) : 599-609.
Almeida RG., Czopka T., Ffrench-Constant C., Lyons DA. (2011) Individual axons regulate the myelinating potential of single oligodendrocytes in vivo. Development , 138 (20) : 4443-50.
Raphael AR., Lyons DA., Talbot WS. (2011) ErbB signaling has a role in radial sorting independent of Schwann cell number. Glia. , 59 (7) : 1047-55.
Lyons DA., Naylor SG., Scholze A., Talbot WS. (2009) Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons. Nat. Genet. , 41 (7) : 854-8.
2014 Project grant, UK MS Society (until 2015)
2013 Shift.ms and Novartis (until 2014)
2012 Institutional Strategic Support fund, University of Edinburgh/Wellcome Trust (until 2013)
2012 Research Prize, Lister Institute of Preventative Medicine (until 2017)
2011 Research Grant, Royal Society (until 2012)
2010 Innovative Award, UK MS Society (until 2011)
2010 International Re-integration Grant, European commission (until 2014)
2009 David Phillips Fellowship, Biotechnology and Biological Sciences Research Council (BBSRC), UK (until 2013)
2006 Development Grant, Muscular Dystrophy Association, USA (until 2008)
2005 Dean’s fellowship award, Stanford University (until 2006)
1999 Department of Anatomy and Developmental Biology Ph.D. Studentship, University College London (until 2003)