SERF1 contribution to protein homeostasis in Drosophila melanogaster. Swagata Ghosh, Adna Karic, Susan Harrison, Douglas Harrison, Brian Rymond. Biology, University of Kentucky, Lexington, KY.

   SERF1 is a gene well conserved in species ranging from bakers yeast to human but its natural biological function is not known in any organism. SERF1 is a candidate modifier of the autosomal recessive form of Spinal Muscular Atrophy (SMA) (Scharf et.al, 1998), the leading genetic cause of human infant mortality. Moreover, SERF1 in C. elegans has been shown to modify proteotoxicity and the accumulation of amyloid aggregates associated with disease related human amyloid proteins, thus indicating its potential role in cellular protein homeostasis (Van Ham et.al, 2010). Here we are investigating the role of SERF1 in cellular protein homeostasis, known to play critical role in tissue aging (Demontis & Perrimon, 2010) using Drosophila melanogaster system. We have created a number of SERF1 mutant backgrounds by imprecise P-element excision, SERF1 mis-expression as well as RNAi mediated down regulation, in order to analyze its impact on protein homeostasis in adult fly muscle. Preliminary observations suggest possible SERF1 contribution to age dependent aggregation of natural ubiquitinated proteins in the adult thoracic muscle tissue. In addition, we are also investigating SERF1 contribution to the Parkinsons disease model of Drosophila in which mutant forms of human alpha synuclein protein are expressed using conventional UAS-Gal4 binary expression system (Feany et.al, 2000). The impact of SERF1 expression on the accumulation of Lewy-body like aggregates of alpha-synuclein in the fly brain will be scored by immune detection. With this study we aim to shed light on SERF1s natural biological function and develop tools helpful in the investigation of age related neurodegenerative disease.