CellLine, a stochastic cell lineage simulator

Summary: We present CellLine, a simulator of the dynamics ofgene regulatory networks (GRN) in the cells of a lineage. Fromuser-defined reactions and initial substance quantities, itgenerates cell lineages, i.e. genealogic pedigrees of cellsrelated through mitotic division. Each cell's dynamics is drivenby a delayed stochastic simulation algorithm (delayed SSA),allowing multiple time delayed reactions. The cells of the lineage can be individually subject to ‘perturbations’,such as gene deletion, duplication and mutation. External interventions,such as adding or removing a substance at a given moment, canbe specified. Cell differentiation lineages, where differentiationis stochastically driven or externally induced, can be modeledas well. Finally, CellLine can generate and simulate the dynamicsof multiple copies of any given cell of the lineage. As examples of CellLine use, we simulate the following systems:cell lineages containing a model of the P53-Mdm2 feedback loop,a differentiation lineage where each cell contains a 4 generepressilator (a bistable circuit), a model of the differentiationof the cells of the retinal mosaic required for color visionin Drosophila melanogaster, where the differentiation pathwaydepends on one substance's concentration that is controlledby a stochastic process, and a 9 gene GRN to illustrate theadvantage of using CellLine rather than simulating multipleindependent cells, in cases where the cells of the lineage aredynamically correlated. Availability: The CellLine program, instructions and examplesare available at http://www.cs.tut.fi/~sanchesr/CellLine/CellLine.html Contact: andre.sanchesribeiro{at}tut.fi Associate Editor: Limsoon Wong     

Learning the language of post-transcriptional gene regulation

A large-scale RNA in vitro selection study systematically identified RNA recognition elements for 205 RNA-binding proteins belonging to families conserved in most eukaryotes.     

HuR and post-transcriptional regulation in vascular aging

HuR(ELAV11(embryonic lethal,abnormal vision)-like 1),a ubiquitously expressed member of the ELAV-like RNA-binding protein family,has been shown to regulate the stability and translation of mRNAs that encode factors regulating cellular senescence,thereby impacting on aging.In this review,we discuss the current knowledge of HuR’s role in vascular cell senescence and vascular aging.     

MicroRNA pharmacogenomics: post-transcriptional regulation of drug response

The field of pharmacogenomics aims to predict which drugs will be most effective and safe for a particular individual based on their genome sequence or expression profile, thereby allowing personalized treatment. The bulk of pharmacogenomic research has focused on the role of single nucleotide polymorphisms, copy number variations or differences in gene expression levels of drug metabolizing or transporting genes and drug targets. In this review paper, we focus instead on microRNAs (miRNAs): small noncoding RNAs, prevalent in metazoans, that negatively regulate gene expression in many cellular processes. We discuss how miRNAs, by regulating the expression of pharmacogenomic-related genes, can play a pivotal role in drug efficacy and toxicity and have potential clinical implications for personalized medicine.