Ashlyn Thorn and Alex Wagner will present their research on April 18th 2013

Ashlyn’s Research Abstract

The Roles of Csk, Src Family Kinases, and the FGF Receptor Heartless in Synaptic Homeostasis

Synaptic homeostasis is the process by which synapses respond to perturbation of normal neurotransmission to maintain set point function and stabilize neuronal signaling.  Aberrant neuronal signaling and activity is associated with a number of neurological disorders including epilepsy, migraine, schizophrenia, ataxia, and myasthenia gravis.  As such, understanding the mechanisms that regulate synaptic homeostasis may provide insight into the underpinnings of these disorders.  To examine these mechanisms, the Frank lab studies synaptic homeostasis at the larval neuromuscular junction of D. melanogaster.  In this system, postsynaptic blockade of glutamate receptors triggers an increase in presynaptic glutamate release that allows the synapse to maintain wild type neurotransmission. This phenomenon and the signaling networks that regulate it have only recently begun to be characterized.  This work has revealed a presynaptic pathway composed of the Eph receptor, the guanine exchange factor Ephexin, the GTPase Cdc42, and voltage-gated Cav2 calcium channels.  In order to identify additional members of this pathway, we undertook and RNAi-based candidate screen.  This screen provided the first evidence that C-terminal Src kinase (Csk) and the fibroblast growth factor receptor Heartless (Htl) may regulate synaptic homeostasis. Verification of these candidates with mutant alleles has confirmed that Csk and Htl are required for synaptic homeostasis.  Csk functions in many cellular contexts to phosphorylate and down-regulate the activity of Src family kinases (SFKs).  As such, we examined the homeostatic roles of src64B and src42A, the SFK homologs in flies, and have shown that both of these SFKs regulate synaptic homeostasis.  Additionally, we have determined that src64B is required in the post-synaptic muscle for homeostatic regulation.  Htl is also required solely in to the muscle, where it may be signaling through src64B.  The tissues in which Csk and src42A function and the downstream targets of the SFKs remain to be determined.

Alex’s Research Abstract

Computational Approaches for Characterizing Inherited Retinal Degenerative Disease

Heritable retinal degenerative diseases such as Retinitis Pigmentosa exhibit extreme genetic and locus heterogeneity, and are observed in only a small percentage of the population.  Despite our current knowledge of disease alleles in a large number of genes, only ~50% of observed cases can be explained by mutations observed in these genes.  In this talk, I discuss computational approaches towards identifying novel disease alleles that may cause retinal degenerative disorders, and using phenotypic information to constrain causative variant hypotheses in a clinical setting.



Posted on April 18, 2013, in Student Seminar. Bookmark the permalink. Leave a comment.

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