Rotation Projects Spring/ Summer/ Fall 2015
There are three research areas in which rotation projects are available:
Axonal guidance and synapse formation.
Rotations in this area involve the question of how modifications of how Wnt signals coordinate the guided migration of motor axons with the accumulation of AChR receptors to the center of muscle cells, thereby bringing into register pre- and postsynaptic components? We have recently shown that wnt11r binds to and acts through the MuSK receptor tyrosine kinase to initiate a downstream signaling pathway reminiscent of the wnt/planar cell polarity (PCP) pathway* and through rab11 mediated endocytosis**.
Techniques involved in this rotation include: microinjection of mRNA and morpholino into embryos, immunohistochemistry, fluorescent microscopy, DNA extraction, genotyping and molecular cloning techniques.
* Jing, L, Lefebvre, J., Gordon, L.R. and Granato, M. 2009. Wnt signals organize synaptic prepattern and axon guidance through the unplugged/MuSk receptor. Neuron 61, 721-733.pdf
** Gordon, L.R., Gribble, K.D., Syrette, C. M. & Granato, M. 2012 . Initiation of synapse formation by Wnt-induced unplugged/MuSK endocytosis. Development, pdf
Axonal de- and regeneration.
We have established a system in which to visualize in real time and in live, intact animals the process of axonal regeneration. Rotations in this area involve 1) the analysis of subcellular events (e.g. mitochondria dynamics) during axonal regeneration in wildtype (injured) but also in animals models for peripheral neuropathies; 2) the analysis of genes and genetic pathways critical for nerve regeneration.
Rosenberg, A., Isaacman-Beck, J, Franzini-Armstrong, C, Granato, M. 2014: Schwann cells and DCC direct regenerating motor axons towards their original path. J. Neuroscience (44) 14668-81. pdf This work is featured in 'This week in the Journal'. Movies for Rosenberg et al.: Movie 1, Movie 2, Movie 3, Movie 4.
Rosenberg, A., Wolman, M, Franzini-Armstrong, C, Granato, M. In vivo macrophage-nerve interactions following peripheral nerve injury. 2012. J. Neuroscience (32), 4440-56. pdf and comment
Simple Learning BehaviorsWolman, M.A., Jain, R.A., Marsden, K.C., Bell, H., Skinner, J., Hayer, K.E., Hogenesch, J.B., Granato, M. 2015: A genome-wide screen identifies PAPP-AA mediated IGFR signaling as a novel regulator of habituation learning. Neuron 85 1200-11.pdf. Preview by Ardie and Rankin pdf. UPENN Press Release!
Rotations in this area involve behavioral testing of neuroactive drugs on their effects on learning/habituation. Rotatiosn projects also involve testing new optogenetic tools to visualize connectivity between identifed hindbrain neurons, and neural activity in these neurons.
Techniques involved in this rotation include: high speed camera measurements, behavioral analysis using automated tracking software, drug applications, DNA extraction, imaging and molecular cloning techniques.
Wolman, M.A., DeGroh, E., McBride, S.M., Jongens, T.A., Granato*, M., Epstein*, J.A. (*senior co-authors) 2014. Modulation of cAMP and Ras signaling pathways improve distinct behavioral deficits in a zebrafish model of Neurofibromatosis Type 1. Cell Reports 8, 2014. pdf.
UPENN Press release
Wolman, M. A., Jain, R.A., Liss, L. & Granato, M. 2011. Chemical modulation of memory formation in larval zebrafish PNAS, 108, 15468-73.