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Huntington's disease, Batten disease, Dictyostelium, calcium signaling, cell-cell adhesion, chemotaxis, cellular homeostasis
My current research program characterizes the cellular and molecular pathways that cause neurodegenerative disorders. Huntington’s disease (HD) is a neurodegenerative disorder caused by mutation in a normally polymorphic region of the huntingtin (Htt) protein. The mutation that causes disease is the expansion of glutamine residues referred to as the polyQ domain (> 37 Q's). HD is a dominantly inherited disease characterized by motor, cognitive and behavioral symptoms, with loss of medium sized spiny neurons in the striatum. There is no therapeutic cure, just palliative care, and death follows between 10-15 years later.While there have been many studies to investigate the physical features of polyQ alone or polyQ embedded in polypeptides, little is known about the molecular impact of the polyQ region on the structure and function of the full-length Htt protein, except that it does not promote ‘self-aggregation’ of the Htt molecule. Thus, alternate model organism strategies are badly needed to complement and facilitate our understanding of the structure-function relationship that exists between the polyQ domain and huntingtin function.
I have developed a deficiency model in the genetically tractable organism Dictyostelium. Strains without the htt gene show that it is critical for cell adhesion, ion homeostasis, cAMP- and Ca2+ chemotaxis, cell polarity and cell fate (Myre, 2011; LoSardo, 2012; Thompson, 2014, Wessels, 2014). These processes have subsequently been found to be altered in various mammalian models of HD.
Specialties: recombinant DNA technologies, nucleic acid sequencing, RNA silencing, gene knockout, RNA purification and analysis by qRT-PCR and RNA-seq, protein analysis using Western blotting, antibody production, immunofluorescence, cell transfection, mammalian cell culture, microscopy (e.g., confocal), flow cytometry in the analysis of the cell cycle and design of synthetic genes for optimal expression in bacteria, yeast and mammalian cells.