 |
Wahlestedt Lab
Department of Neuroscience
Identification and Functional Analysis of Noncoding and Antisense Transcript
Most likely conventional protein-coding genes account for only a minority of human RNA transcripts. A substantial component of the full-length mouse and human cDNA sets that we and others have analyzed does not contain an annotated protein-coding sequence and most likely corresponds to noncoding RNA. Many of the noncoding sequences constitute natural antisense RNA transcripts. We have shown that the majority of noncoding RNAs identified to date have substantial conservation across species. Moreover, we have shown that many noncoding RNA and antisense transcripts have differential expression under various conditions and can affect conventional gene expression.
RNA Interference and Development of High-throughput Genomics Technology
RNA interference has become one of the most important gene manipulation technologies. Short interfering RNA, the inducer of RNA interference in mammals, can be used to elucidate gene functions by rapidly silencing expression of a target gene. Today, short interfering RNAs are widely used as research tools and have potential for becoming therapeutic agents. We have built a portfolio of short interfering RNA technology. In this package we have a powerful short interfering RNA vector system, a validation system, and a design system, all of which are unique. Combining these technologies with the high-throughput chemistry for on-chip DNA synthesis, we have set up a system for constructing short interfering RNAs. Finally, we have also introduced the use of locked nucleic acids in short interfering RNAs and have shown a range of beneficial properties of these agents.
G Protein-Coupled Receptors as Drug Targets
More than half of known drugs bind to G protein-coupled receptors (GPCRs). We continue our long-standing work on GPCRs, particularly with neuropeptide Y receptors. At Scripps Florida, these efforts form part of the drug discovery program. Moreover, during the past year, we published on our human GPCR database, which contains polymorphism data, that is, data that point to inter-individual differences in GPCR sequences. Information on polymorphisms may be increasingly important in drug discovery and development efforts.
Deep Sequencing Approaches
We are pursuing drug discovery related to several human disorders that affect the brain. Our goal is to identify biomarkers that are associated with such common disorders. We wish to understand what makes certain individuals susceptible and how their responses to drug treatment may differ (pharmacogenomics). We are involved in genotyping DNA from patients with major depression, alcoholism, diabetes, obesity, Alzheimer's disease, Parkinson's disease, and attention deficit/hyperactivity disorder.
|
|
