Research Report 2010 - MDC

Wei ChenStructure of the GroupGroup LeaderDr. Wei ChenScientistsDr. Yuhui HuDr. Andreas DoeringGraduate StudentsNa LiHui KangWei SunYongbo WangRaghu Bhushan (till June 2009)Novel sequencing technology,miRNA regulation and humanmolecular geneticsThe recent introduction of massive parallel sequencing technology has revolutionizedgenomic research. These so-called next generation sequencing platforms, such asRoche/454, Illumina/solexa and ABI/Solid system can sequence DNA orders of magnitudefaster and at much lower cost than conventional Sanger method. With their incrediblesequencing capacity, my lab has been focused on developing and implementing variousgenomic assays based on this new generation of sequencers. Apart from offering servicesto the institute as a core facility provider, we are now applying the assays in studyingtranscriptional and posttranscriptional regulation of miRNA genes, as well as identifyinggenetic factors underlying human diseases.Transcriptional and posttranscriptional regulationof miRNA genesYuhui Hu, Andreas Doering, Na Li, Hui Kang, Wei SunMiRNAs are small non-coding RNAs that control theexpression of target genes at the posttranscriptionallevel. Recently, more and more miRNAs have been implicatedin a variety of biological processes.Whereas muchattention has been focus on finding the target genesregulated by miRNAs, little is known about the systemwhich regulates miRNA expression. One major focus ofmy lab is to study transcription and posttranscriptionalregulation of miRNA genes. In the study of transcriptionalregulation, we are involved in genome wide discoveryof miRNA promoters in pre-B cells using ChIPseq,mRNA-seq and small RNA sequencing methods.It has been demonstrated that the Drosha or Dicer processingof individual miRNA can be regulated. Though,it is yet not known that how generalized the phenomenaare.We are therefore interested in studying the posttranscriptionalregulation of miRNAs, especially regulationof Dicer processing at the genomic level bygenome-wide profiling of miRNA precursor (premiRNA)and mature miRNA from the same sample andcomparing their relative abundance across differentsamples. Currently, we are developing a novel assay toefficiently profile pre-miRNA based on new sequencingtechnology.Characterisation of breakpoints in disease-associatedbalanced chromosome rearrangementsYuhui Hu, Andreas DoeringBalanced chromosome rearrangements (BCRs) cancause genetic diseases by disrupting or inactivatingspecific genes, and the characterization of breakpointsin disease-associated BCRs has been instrumental inthe molecular elucidation of a wide variety of geneticdisorders. However, mapping chromosome breakpointsusing traditional methods is rather laborious and timeconsuming.In addition, the resolution is often insufficientto unequivocally identify the disrupted gene. To194 Berlin Institute of Medical Systems Biology