The Simon And Katya Michaeli Bioinformatics Laboratory

                 For The Research Of The Genome

Alternative splicing is a mechanism by which more than one mRNA transcripts are generated from the same mRNA precursor. Recent findings suggest that >90% of human genes are alternatively spliced, and we demonstrated that human contain the highest level of alternative splicing. Alternative splicing can be specific to tissue type, environment or developmentally regulated. Splice variants have also been implicated in various diseases including cancer. Detection of these variants will enhance our understanding of the complexity of the human genome and provide disease-specific and prognostic biomarkers. Our group has made seminal contributions to our understanding of the acquisition of complexity in the expression of genomic information through alternative mRNA splicing, and the involvement of this process in genetic disorders and cancer.

The broad focus of our laboratory is on regulation of splicing of pre-mRNA and the importance of alternative splicing in the generating transcriptomic diversity unique to our species. We study mechanisms of alternative splicing regulation using a combination of computational and experimental (mostly molecular biology tools) methods. We also study the potential link between DNA packaging by histones and epigenetic modifications and how these effect processing of pre-mRNA. An increasing body of evidence indicates that transcription and splicing are coupled and it is accepted that chromatin organization and DNA modification regulate transcription. Little is known, however, about the cross-talk between chromatin structure and splicing. We continue to examine how RNA polymerase II and DNA modifications mediate cross-talk between chromatin structure and splicing (see Schwartz et al., Nature Structural and Molecular Biology, 2009). We also study splicing-related genetic diseases like the neurodegenerative disease Familial Dysautonomia and the link between splicing and cancers (especially ovarian, breast, leukemia) using molecular and cellular methods. Finally, we also study the roles that splicing plays in microRNA (miRNA) regulation.