Lily Paemka and Mathew Faron to present in Student seminar on July 21st 2011.
Evaluating THE ROLE OF Prickle mutations in Human PROGRESSIVE MYOCLONIC EPILEPSY
Epilepsy is a complex genetic brain disorder characterized by seizures that afflicts ~1% of the population. For over 70% of patients, the underlying cause of epilepsy remains unknown and seizures remain uncontrolled in about 25%. Progressive Myoclonic Epilepsy (PME) is a rare epilepsy characterized by neurodegeneration, myoclonus, and generalized seizures. Bassuk et. al identified mutations in Prickle1 and Prickle2 responsible for PME in families and in the general population.
The Prickle genes are expressed in the developing nervous system and mature neurons, involved Planar Cell Polarity and are players in Wnt-mediated signaling; a cascade likely critical in neurodevelopment and neurodegeneration. Studies have shown that Prickle mutations are associated with seizures in Drosophila and mice. In zebrafish, overexpression of mutant Prickle resulted in compromised protein function. My ongoing and future experiments include characterizing the effect of Prickle mutations on protein-protein interactions, neuronal differentiation, calcium activation, and REST-mediated transcriptional repression. To resolve some of these questions, I have established stable lines expressing wild-type and mutant Prickle 1 and Prickle 2. Findings from these studies would clarify molecular mechanisms by which Prickle mutations alter neuronal function and help identify novel therapeutic targets.
BACKGROUND FOR MATHEW FARON’S TALK
Francisella tularensis is a gram negative facultative intracellular pathogen and is the causative agent of tularemia. Though tularemia is not a common disease, its low infective dose and high mortality rate for untreated infections has led to F. tularensis being classified as a class A select agent that could be utilized as a bioterrorism weapon. Francisella research has focused on how it evades the host immune system and survives and replicates within both macrophages and neutrophils. However, little is known about how Francisella adapts and survives within such hostile environments. What has been shown is that Francisella utilizes a 17 gene pathogenic island which allows Francisella to escape from the phagosome and replication within the cytosol. Several regulators have been identified, but the molecular mechanisms are unknown. Our research has focused on characterizing these regulators and their role in virulence. Currently I have identified several environmental signals that significantly alter FPI expression.