The Faust lab pursues two projects: defining the role of isopentenyladenosine and elucidating the defects in neuronal ceroid lipofuscinoses.

Isopentenyladenosine

Isopentenyladenosine (i6A) is an isoprene-modified nucleoside found in tRNAs. Its conserved presence in specific tRNAs and at a specific location (immediately 3' to the anticodon) indicates that i6A has a critical function in tRNA biology. The goal of this project is to identify the function for this modified nucleoside. Using a novel identification procedure, we discovered that two i6A-containing tRNAs in CHO cells recognize specific UGA codons. Normally, UGA is a stop codon. We hypothesize that the isopentenyl moiety is important for opal suppressor activity of i6A-tRNAs. Current work is directed at testing that hypothesis.

Neuronal Ceroid Lipofuscinoses

Neuronal ceroid lipofuscinosis (NCL) is a set of neurodegenerative genetic diseases which affect primarily children. Mutations in seven mammalian genes produce the same clinical, histological, and biochemical phenotypes ultimately leading to death. The primary defects causing this set of diseases are not known. Although four NCL genes have been identified, the functions of the gene products are not defined clearly. Our studies focus on mouse models of NCL. Using a positional cloning strategy, we are identifying a murine mutation which is homologous to a unknown human NCL gene. Additionally, biochemical and cell biological experiments are in progress defining the function for two other NCL gene products.