seminars

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IMCB PI Seminar (2007 - 2009)

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PI Seminar Series 2007-2009 (PDF)

upcoming Seminars

Selected Seminar

Date:	29 August 2008
Time:	11:00am \| Breakthrough Theatrette, Level 4 , Matrix.
Speaker 1:	Dr. Igor V. Kurochkin
Title:	Exosome-mediated transfer of RNA as a means of information exchange in multicellular organisms

Abstract

Dr. Igor V. Kurochkin, RIKEN Advanced Science Institute (ASI), Japan.

Intercellular communication is crucial for the coordinated action, in time and space, of the enormous number of various cells comprising the human body. There is a multitude of ways employed by the organism to accomplish this task. The discovery of membrane microvesicles secreted by various eukaryotic cells has established a novel type of intercellular communication. Recent work revealed that exosomes (the smallest microvesicles described so far) released from human and mouse mast cells contain a subset of cellular mRNAs (~1300), many of which (~270) are not present in the cytoplasm of donor cells. Exosomes were also found to carry 121 miRNAs some of which were enriched in these microvesicles. Moreover, mRNA delivered by exosomes to recipient cells was translated into protein. Thus secretory exosomes may represent a new means of exchange of genetic information between cells and in this respect they can also be referred to as “informosomes”. These initial studies are surely just the tip of the iceberg in what is likely to become a rapidly accelerating field of research. I will review recent findings in exosome biology and discuss (i) possible mechanisms involved in the biogenesis of exosomes, (ii) signals that might be responsible for the active sorting of RNA to exosomes, (iii) determinants that could make certain precise targeting of exosomes to their destinations and (iiii) various possible interpretations of the RNA signal by the recipient cells. The main hypothesis of this presentation is that a common informational field exists in the body that represents a dynamic system capable organizing the body adaptive response to internal and environmental changes. This field is mediated by constantly circulated exosomal RNA that serves to gather and exchange the information between various cell types, tissues and organs. If secreted RNA indeed plays a key role in the exchange of genetic information between the cells, it can be expected that deregulation of exosome release, targeting or sorting of its components may lead to severe pathological defects in the respective organisms. If confirmed, the pharmacological modulation of the exosome pathway may offer a novel and alternative to current approach to treat various health disorders.

Date:	29 August 2008
Time:	11:30am \| Breakthrough Theatrette, Level 4 , Matrix.
Speaker 2:	A. Prof. Igor V. Kurochkin
Title:	Splice Regulatory Motif Discovery in Exons

Abstract

A. Prof. Christian Schoenbach, Nanyang Technology University (NTU), Singapore.

Alternative splicing is an important mechanism that contributes to the phenotype diversity of mammalian cells. Up to 60% of mouse multi-exon genes are alternatively spliced. Yet, the regulation of splicing, that is when and where an exon is skipped or an alternative splice site is used, remains to be fully decoded. Splice signals flanking alternative exons are often weaker because they deviate from the consensus splice motifs. However exonic splice enhancers (ESE) can offset the weaker splicing signals. ESE are 6 to 12-mer motifs that are recognized by spliceosomal proteins. Position weight matrix-based probabilistic modeling is one of many techniques that has helped to identify ESE in alternative exons. We were interested in identifying without prior assumption on splice site strength and in a position-independent way motifs that may differentiate alternative exons from skipped or constitutive exons. Considering the similarities to detecting cis-regulatory elements such as potential transcription factor sites we applied a word enumeration method and an expectation maximization method to a data set described by Wang et al. (2004). Using the word enumeration method we identified 400 mouse (400 human) 6-mer motif candidates. Of these 37% (48%) were unique new exon-type specific candidates. Forty-five percent of all mouse (42% human) 6-mers corresponded to known ESE including experimentally confirmed motifs. Results obtained with the expectation maximization method produced between 46% to 71% (44%-68%) mouse (human) novel splice regulatory motif candidates. The functionality and strength of the motifs and the relationships between motif strength and motif occurrence in particular exon types remains to be examined more closely in future experiments. However, recent findings reported in the literature supported the potential role of some of our candidates in splicing regulation. For example, mouse alternative exon-specific motif CGTGAG is identical to ASSET-reported splicing tag associated with intron retention.

Host: Dr. Frederic Bard.