Center for Computational Molecular Biology Seminar
Abstract: We have used methods for purifying endogenously formed mRNP complexes and identifying their associated mRNA targets using microarray technologies (ribonomic profiling). This has enabled the genomic-scale identification of many mRNA targets of RNA-binding proteins ( RBPs) and has provided new insights into the principles governing post-transcriptional gene regulation. Using Affymetrix tiling arrays for human chromosomes 21-22, we have extended our findi ngs and determined the associations of both coding and noncoding RNAs for several RBPs including HuR, IMP, La and PABP. Tiling arrays are designed to exhaustively span a designated genetic sequence in a high-density manner to include all coding and noncoding regions e xclusive of highly repeated regions. This allows for the exhaustive and unbiased analysis of mRNP associated RNA, annotated and un- annotated, as well as the identification of alternative spliced products and there association with RBPs. The tiling array platform used in this study interrogates on average, every 35 bases of the approximately 35 million base pairs of chr 21-22 (Kapranov et al., 2002). Previously, using tiling arrays, it was unexpectedly observed that a great deal more genomic sequence was transcribed into RNA than can currently be accounted for using our present annotation. Limited analysis of these novel transcripts revealed that they possess little protein coding potential and frequently occupy an antisense orientation relative to well-characterized coding transcripts. By combining ribonomic profiling with tiling arrays, our studies indicate that in addition to targeting predicted mRNAs, many of the noncoding RNAs expressed from the genome also appear to be associated with RBPs in a specific and selective manner. In addition to having significant uniqueness in exonic, intronic and novel RNA specificity, we also observe potentially meaningful overlaps in the RNA subset affinities of the RBPs that we targeted. The UTRs of many mRNAs contain sequence and structural motifs that are used to regulate the stability, localization and trans latability of mRNA. Unfortunately, the consensus sequence s for these motifs frequently have significant variability an d are only loosely characterized making the use of simple alignment tools inadequate for the discovery of new RNA regulatory motif s. Additionally, many software tools utilize adaptive techniques requiring training. We have generated a collection of positive control Training UTR datasets called "the UAlbany TUTR collection" which is meant to be used as blind training/test sets that contain a previously characterized RNA motif conforming to a defined consensus. The basic training sets have been generated with associated indexes and "answer sets" produced to identify where the previously characterized RNA motif (e.g. the IRE, ARE, SECIS, etc.) resides in each sequence. The UAlbany TUTR collection is meant to be a shared resource and has been made available to a number of researchers for software testing. The strengths and weaknesses of different algorithms to successfully identify different consensus motifs will be presented. Additionally, we are presently developing customized tiling array based ribonomic profiling technology which enables the genomic-scale foot-printing of RBP binding sites. Examples of this technology will also be discussed.
Center for Fluid Mechanics
and
The Fluids, Thermal and Chemical Processes Group
of
The Division of Engineering
Seminar Series
University of Michigan, Ann Arbor, MI | |
Abstract: We extend recent single-molecule imaging methods to the study of the interactions of DNA polymers with surfaces in the presence of flow or electric fields. These interactions are of importance in the development of microfluidic devices for processing of DNA and other large molecules for genomics applications, and to learn how proteins interact with DNA in cellular processes such as DNA repair, transcription, etc. Using single-molecule optical microscopy and atomic force microscopy experiments and Brownian dynamics simulations of DNA molecules, combined with fluid mechanics analyses, we consider isolated DNA molecules near adsorbing and non-adsorbing walls in the presence of flows. In particular, we explore ways in which DNA unraveling can be optimized through manipulation of flow and electric fields, and how one can design theoretical models to explain the unraveling processes.
Stochastic Systems Seminar
PDE Seminar
Abstract: Gradient drift instabilities are instabilities which occur in atmospheric space plasmas. They exist because the plasma interact with neutral particles, which create a destabilizing dragging force. I will present a model specifically derived to study these instabilities, the so-called striation model. This model is a relaxation and low beta limit of the ideal MHD equations. It is a purely hydrodynamic incompressible system. I will explain how to obtain linear and nonlinear insatbility results about a generic class of smooth stationary profiles, by adapting the results of Y. Guo & H.J. Hwang on the Rayleigh-Taylor equations. This work is a collaboration with C. Besse, P. Degond, and H.J. Hwang.
I will also discuss the effects of kinematic viscosity, in the framework of this model. Contrary to what could be expected, no viscous damping occurs in the system. The results obtained show evidence that viscosity may have interesting effects on instabilities.
PDE Seminar
Abstract: The dynamics of a charged particle under axisymmetric gravitational and electromagnetic forces will be studied. The physics of the problem will be discussed and will be modeled by a system of ordinary differential equations. Then several questions on bifurcations and stability of equatorial orbits will be analyzed. Finally, a very curious and not fully understood phenomenon, the so called "spokes" in Saturn's B ring, will be discussed in the context of the results presented in the talk.
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