Epigenetics of SNCA and APOE Genes and Lewy Body Dementia

Lewy Body Dementia (LBD) is a neurodegenerative disease characterized by rapid cognitive decline, Parkinson's-like motor issues, hallucinations and eventually death. Because LBD displays traits similar to other neurodegenerative conditions, such as Alzheimer's disease (AD), researchers have sought more reliable, specific ways to diagnose LBD. Recent studies have singled out some candidate genes that could serve as potential biomarkers for LBD: SNCA and APOE. Epigenetic modifications, specifically hypomethylation, in SNCA and APOE genes is positively correlated with the development of Lewy Body Dementia, which suggests that these genes could be potential biomarkers to diagnose LBD if their mechanistic contribution to LBD development is better understood.Bruner, KatherineMolecular Bioscience

Rational design of an orthogonal tryptophanyl nonsense suppressor tRNA

While a number of aminoacyl tRNA synthetase (aaRS):tRNA pairs have been engineered to alter or expand the genetic code, only the Methanococcus jannaschii tyrosyl tRNA synthetase and tRNA have been used extensively in bacteria, limiting the types and numbers of unnatural amino acids that can be utilized at any one time to expand the genetic code. In order to expand the number and type of aaRS/tRNA pairs available for engineering bacterial genetic codes, we have developed an orthogonal tryptophanyl tRNA synthetase and tRNA pair, derived from Saccharomyces cerevisiae. In the process of developing an amber suppressor tRNA, we discovered that the Escherichia coli lysyl tRNA synthetase was responsible for misacylating the initial amber suppressor version of the yeast tryptophanyl tRNA. It was discovered that modification of the G:C content of the anticodon stem and therefore reducing the structural flexibility of this stem eliminated misacylation by the E. coli lysyl tRNA synthetase, and led to the development of a functional, orthogonal suppressor pair that should prove useful for the incorporation of bulky, unnatural amino acids into the genetic code. Our results provide insight into the role of tRNA flexibility in molecular recognition and the engineering and evolution of tRNA specificity

The diploid genome sequence of Candida albicans

We present the diploid genome sequence of the fungal pathogen Candida albicans. Because C. albicans has no known haploid or homozygous form, sequencing was performed as a whole-genome shotgun of the heterozygous diploid genome in strain SC5314, a clinical isolate that is the parent of strains widely used for molecular analysis. We developed computational methods to assemble a diploid genome sequence in good agreement with available physical mapping data. We provide a whole-genome description of heterozygosity in the organism. Comparative genomic analyses provide important clues about the evolution of the species and its mechanisms of pathogenesis