Abstract

The importance of RNA and chromatin in the multiple levels of regulation that ensure proper functioning of the eukaryotic transcriptome and proteome has been increasingly recognized in recent years. Converging lines of evidence have led to a clearer realization that many of these processes are interrelated. For example, there is continuous feed-forward crosstalk among the processes of chromatin organization, transcription, and pre-mRNA splicing. Furthermore, it has now become apparent that chromatin structure and epigenetic markers influence the recognition of exons and splice site choices. The multiple layers of regulation that function jointly in chromatin organization, transcription, and RNA processing will be presented.

 

The Ast's Group

Alternative splicing is a mechanism by which more than one mRNA transcripts are generated from the same mRNA precursor. Recent findings suggest that almost all the human genes undergo alternatively spliced, and we demonstrated that humans contain the highest level of alternative splicing. Alternative splicing can be specific to tissue type, environment or developmental stage. 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 complexity in genomic expression through alternative mRNA splicing and the involvement of this process in genetic disorders and cancer.

The broad focus of our research is on pre-mRNA splicing regulation and the importance of alternative splicing in generating transcriptomic diversity unique to our species. We also study the potential link between DNA packaging and splicing, and are interested in the effects nucleosomal positioning, specific histone modifications and other epigenetic characteristics have on pre-mRNA processing. 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 also study splicing-related genetic diseases like the neurodegenerative disease Familial Dysautonomia and the link between splicing and various cancer types. Finally, we study the role splicing plays in microRNA (miRNA) regulation as well.

 

The importance of RNA and chromatin in the multiple levels of regulation that ensure proper functioning of the eukaryotic transcriptome and proteome has been increasingly recognized in recent years. Converging lines of evidence have led to a clearer realization that many of these processes are interrelated. For example, there is continuous feed-forward crosstalk among the processes of chromatin organization, transcription, and pre-mRNA splicing. Furthermore, it has now become apparent that chromatin structure and epigenetic markers influence the recognition of exons and splice site choices. The multiple layers of regulation that function jointly in chromatin organization, transcription, and RNA processing will be presented.

Alternative splicing is a mechanism by which more than one mRNA transcripts are generated from the same mRNA precursor. Recent findings suggest that almost all the human genes undergo alternatively spliced, and we demonstrated that humans contain the highest level of alternative splicing. Alternative splicing can be specific to tissue type, environment or developmental stage. 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 complexity in genomic expression through alternative mRNA splicing and the involvement of this process in genetic disorders and cancer.

The broad focus of our research is on pre-mRNA splicing regulation and the importance of alternative splicing in generating transcriptomic diversity unique to our species. We also study the potential link between DNA packaging and splicing, and are interested in the effects nucleosomal positioning, specific histone modifications and other epigenetic characteristics have on pre-mRNA processing. 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 also study splicing-related genetic diseases like the neurodegenerative disease Familial Dysautonomia and the link between splicing and various cancer types. Finally, we study the role splicing plays in microRNA (miRNA) regulation as well.

Abstract:
Sequence census methods couple high-throughput DNA sequencing to biochemical assays and are transforming standard functional genomics assays into powerful genome-wide probes of biochemical activity. We will survey the plethora of *-Seq assays that have been developed and describe examples of how computational advances are going hand-in-hand with the biotechnology to enable biological discovery.

Biography
I am a computational biologist working in genomics. My career began in comparative genomics, and initially I was interested in genome alignment, annotation, and the determination of conserved regions using phylogenetic methods. I contributed to the mouse, rat, chicken and fly genome sequencing consortia, and the ENCODE project. More recently I've become focused on functional genomics, which includes answering questions about the function and interaction of DNA, RNA and protein products. I'm particularly interested in applications of high-throughput sequencing to RNA biology.

I'm also interested in algorithms, statistical methodology, and mathematical foundations for computational genomics. These interests are reflected in my appointments across different departments and colleges: Mathematics, Molecular & Cell Biology, and Electrical Engineering & Computer Science. My group includes students and postdocs from Computer Science, Mathematics, Bioengineering, Molecular and Cell Biology and Statistics.

Abstract

DNA is an information carrying molecule, encoding not only for the RNAs and proteins that perform the functions necessary for cellular and organismal viability, but also encoding the instructions for when, where and under what conditions those functional molecules are expressed. Most of my career has been devoted to studying the signals, cis-regulatory elements, in DNA and RNA that controls various aspects of gene expression. This talk will provide some background on the nature of the signals we seek, some history of approaches to find them, how current technology facilitates the search and where I think the field is headed.

Biography

Gary Stormo is the Joseph Erlanger Professor in the Department of Genetics and the Center for Genome Sciences and Systems Biology at Washington University School of Medicine in St Louis. He received his B.S. degree in biology from the California Institute of Technology and his and Ph.D. in molecular biology from the University of Colorado at Boulder. He remained at the University of Colorado as a faculty member in the Department of Molecular, Cellular and Developmental Biology until joining the faculty at WUSM in 1999. Beginning with his graduate thesis work he has combined experimental and computational approaches to understanding gene regulation. Most of that work has focused on identifying, modeling and predicting regulatory sites in DNA and RNA and their contributions to regulatory networks that control gene expression in vivo.

Abstract
How could we evaluate research and researchers? Reproducibility underpins the scientific method: at least in principle if not practice. The willing exchange of results and the transparent conduct of research can only be expected up to a point in a competitive environment. Contributions to science are acknowledged, but not if the credit is for data curation or software. From a bioinformatics view point, how far could our results be reproducible before the pain is just too high? Is open science a dangerous, utopian vision or a legitimate, feasible expectation? How do we move bioinformatics from one where results are post-hoc "made reproducible", to pre-hoc "born reproducible"? And why, in our computational information age, do we communicate results through fragmented, fixed documents rather than cohesive, versioned releases? I will explore these questions drawing on 20 years of experience in both the development of technical infrastructure for Life Science and the social infrastructure in which Life Science operates.

Biography
Carole Goble is a full professor in Computer Science at the University of Manchester, UK. She has an international reputation in Semantic Web, Distributed computing, and Social Computing for scientific collaboration. She is a member of the Software Sustainability Institute UK. She directs the myGrid project, which produces the widely-used open source Taverna workflow management system; myExperiment, a social web site for sharing scientific workflows; the Biocatalogue of web services for the life sciences; and the SEEK for storing, sharing and preserving Systems Biology outcomes.

In 2008 Carole was awarded the inaugural Microsoft Jim Gray award for outstanding contributions to e-Science. In 2010 she was elected a Fellow of the Royal Academy of Engineering. In 2012 she was nominated for the Benjamin Franklin award for open science in Biology.