Bioinformatics touches upon every project we have in our lab.
RNA interference is a double-stranded RNA-dependent post-transcriptional gene knockdown method, with a wide range of experimental applications. However, the precise rules governing the effectiveness of shRNAs (short hairpin RNAs, one of the
types of RNAi molecules) are not yet known. In addition, most of the current research is on siRNA (small interfering RNA) methods, which, while similar to shRNAs, differ substantially in delivery and processing methods.
It is uncertain which siRNA design rules apply to shRNAs and to what extent, and whether there may be additional shRNA-specific rules. This uncertainty is complicated by the complexity of RNA structure, the presently unclear restrictions on small RNA biogenesis and loading into RNAi silencing complexes, and additional post-transcriptional regulatory biology.
Our lab has a foot in the 'dry' and 'wet' worlds, we we use computational approaches to dissect and help understand biology. In one of the projects in the lab we are developing an open-source and easily extendable shRNA design program implementing newly discovered shRNA design rules. An exciting aspect of this project is that it is based on deep experimental data and the power of computational biology.
Epigenetics is a major area of study in our lab, and we are one of the NIH Reference Epigenome Mapping Centers, which is dedicated to the genome-scale mapping
of epigenetics marks and transcriptome analysis. The epigenome is the dynamic interface between our changing environment and the static genome, and understanding it is a goal of immense importance to human health. We are presently mapping reference cell epigenomes of the brain, breast, blood and approved embryonic stem cells, inclusive of males and females and different racial groups. This cooperative work will transform our understanding of the short and long-lasting consequences of environment impact on human health and disease.
Our team consists of scientists at UCSF, UC Davis, UCSC, and the British Columbia Genome Sciences Centre and has a broad expertise. We are focusing on cell relevant to human health and complex disease including cells from the blood, brain, breast and U.S. Government-approved lines of human embryonic stem cells. We envision that our group in conjunction with the other REMC teams, the EDACC, ENCODE, future EHHD (Epigenetics of Human Health and Disease) centers and the NIH Roadmap program will develop methods, tools and reference epigenome maps for the research community that will make the promise of epigenetics in understand and treating human complex disease a reality.
Our reference epigenomes will enable new disciplines including human population epigenetics, comparative epigenomics, neuroepigenetics, and therapeutic epigenetics for tissue regeneration and reversal of disease. This project is producing a rich dataset that will require years of bioinformatic analysis for the field.
Whole genome phenotypic screens. A unique aspect of our lab at UCSF is our use of whole genome pooled shRNA library technologies. We have created many libraries, the largest being over 600,000 shRNA elements. We have developed powerful protocols that require statistics and bioinformatic analysis of the 'hits'. We are a member of the Biomedical Informatics Program at UCSF and intersect with other group here to implement computational approaches in our wet bench science.