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Vicente Pelechano Group

Transcriptional basis of non-genetic cellular heterogeneity

One of the biggest challenges in biology is to understand how apparently identical cells respond differently to the same stimulus. In some cases this differential behaviour can be explained by alterations of their genetic material, however in other cases identical (clonal) cells can also display phenotypically heterogeneous responses. We use state of the art genomic technologies to study the regulatory mechanism leading to the appearance of divergent gene expression programs in clonal populations of cells.

In the last few years, the biomedical field has suffered a revolution thanks to the development of the massive parallel sequencing technologies. Now we can obtain the complete genetic information of a person and analyse how this information is being used in a few days and with a limited cost. This technologies makes possible a kind of research that was unthinkable a few years back. In the past we have developed a diversity of novel genome-wide approaches to study eukaryotic gene expression using both budding yeast and mammalian cells. By simultaneously sequencing both the 5’ and 3’ ends of each RNA molecule (TIF-Seq), we showed that the complexity of overlapping transcript isoforms had been greatly underestimated. More recently, we have shown how the existence of widespread co-translational mRNA degradation allows to study ribosome dynamics by sequencing mRNA degradation intermediates (5P-Seq). In addition, we have also developed new approaches for the study of other relevant biological questions, such as chromatin structure, single-cell transcriptomics, RNA polymerase elongation or isoform-specific interactions with RNA binding proteins.

Our group, combining experimental and computational work, aims to develop and apply novel genome-wide techniques to study eukaryotic transcription to address fundamental biological questions with medical implications. We are specially interested in the case of drug-tolerant cancer persister cells that, although genetically sensitive to a drug, do not respond to it. To deliver an integrated view of the mechanisms driving their appearance, as well as to refine our knowledge of the basic process of gene expression, we study both budding yeast and human cell lines at three levels of the gene expression process: epigenetic status, transcript isoform usage and post-transcriptional mRNA regulation

Our group is affiliated to both MTC and the Science for Life Laboratory (http://scilifelab.se/) where our lab is located. Group homepage/external homepage:
http://pelechanolab.com

Selected Publications

30799147

30707695

30373810

30059503

29549331

29027175

28866863

28637236

28549188

A global genetic interaction network maps a wiring diagram of cellular function
M. Costanzo, B. VanderSluis, E. N. Koch, A. Baryshnikova, C. Pons, G. Tan, W. Wang, M. Usaj, J. Hanchard, S. D. Lee, V. Pelechano, E. B. et al
Science, 2016; 353 (6306): aaf1420 DOI: 10.1126/science.aaf1420

27183194

26820793

26046441

26040288

25583149

25550430

24967623

24569168

23615609

Group Members

Alisa AlekseenkoDoktorand, Forskarstuderande

alisa.alekseenko@ki.se

Donal BarrettLaboratorietekniker

donal.barrett@ki.se

Eva BrinkmanPostdoc

eva.brinkman@ki.se

Susanne HuchPostdoc

susanne.huch@ki.se

Ryan HullPostdoc

ryan.hull@ki.se

Bingnan LiPostdoc

bingnan.li@ki.se

Sueli MarquesSenior lab manager

sueli.marques@ki.se

Lilit NersisyanPostdoc

lilit.nersisyan@ki.se

Yerma Pareja SanchezDoktorand, Forskarstuderande

yerma.pareja.sanchez@ki.se

Vicente Pelechano GarciaForskarassistent

vicente.pelechano.garcia@ki.se

Jose Perez OrtinAnknuten

jose.perez.ortin@ki.se

Jingwen WangPostdoc

Jingwen.Wang@ki.se

Xiushan YinSenior forskningsspecialist

xiushan.yin@ki.se

Yujie ZhangForskarstuderande

yujie.zhang@ki.se