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Genetic Systems

Group Leader:



icrea

September 2009- ICREA Research Professor

December 2006- Group Leader, EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation, Barcelona.

2004-2006 Postdoctoral Fellow, Fraser Lab, The Wellcome Trust Sanger Institute

2004 PhD University of Cambridge

2000 BA Natural Sciences, University of Cambridge 

Our lab is part of the EMBL/CRG Systems Biology Unit. 

We are funded by the European Research Council (ERC),  the EMBL-CRG Program, MICINN, AGAUR, ERASySBio+, and ICREA.

We are located in the Centre for Genomic Regulation which has a beautiful beachfront location in the Barcelona Biomedical Research Park.

Summary

To what extent is it possible to predict the phenotypic differences amongst individuals from their completely sequenced genomes?  We use model organisms (yeast, worms) and computational analyses to understand when you can, and why you cannot, predict the biology of an individual from their genome sequence.  Individuals are thankfully all different, and our aim is to understand how these differences originate in the interactions between genetic, environmental, life history, parental and stochastic sources of variation.

Research articles

 

Schuster-Böckler B. Lehner B. Chromatin organization is a major influence on regional mutation rates in cancer cells. Nature. 2012 488(7412)504-7.
Semple JI, Biondini L, Lehner B. Generating transgenic nematodes by bombardment and antibiotic selection. Nature Methods. 2012 Jan 30;9(2):118-9.  
**For information on antibiotic selection vectors and protocols, please see the link at the bottom of the page **

Casanueva MO, Burga A, Lehner B. Fitness trade-offs and environmentally-induced mutation buffering in isogenic C. elegans. Science2012 Jan 6;335(6064):82-5

Burga A, Casanueva MO, Lehner B. Predicting mutation outcome from early stochastic variation in genetic interaction partners. Nature. 2011. 480:250-254

Jelier R, Semple JI, Garcia-Verdugo R, Lehner B. Predicting phenotypic variation in yeast from individual genome sequences Nature Genetics. 2011; 43(12):1270-4.

Francesconi M, Jelier R, Lehner B. Integrated genome-scale prediction of detrimental mutations in transcription networks. PLoS Genetics. 2011 May;7(5):e1002077.

Vavouri T, Lehner B. Chromatin organization in sperm may be the major functional consequence of base composition variation in the human genome. PLoS Genetics. 2011 Apr;7(4):e1002036.

Lehner B. Conflict between noise and plasticity in yeast. PLoS Genetics. 2010 6(11): e1001185.

Semple J, Garcia-Verdugo R, Lehner B. Rapid selection of transgenic C. elegans using antibiotic selection. Nature Methods. 2010 7(9):725-7.

Lee I*, Lehner B*, Vavouri T, Shin J, Fraser AG*, Marcotte EM* Predicting genetic modifier loci using functional gene networks. Genome Research. 2010. 20(8):1143-53

Lehner B. Genes Confer Similar Robustness to Environmental, Stochastic, and Genetic Perturbations in Yeast. PLoS One. 2010; 5(2): e9035.

 

Dzyubachyk O, Jelier R, Lehner B, Niessen W, Meijering E. Model-based approach for tracking embryogenesis in Caenorhabditis elegans fluorescence microscopy data.  Conf Proc IEEE Eng Med Biol Soc. 2009;1:5356-9.

Vavouri T, Semple JI, Garcia-Verdugo R, & Lehner B. Intrinsic protein disorder and interaction promiscuity are widely associated with dosage sensitivity. Cell.  2009. 138:198–208.

Bossi A, Lehner B. Tissue specificity and the human protein interaction network. Molecular Systems Biology. 2009. 5:260.

Vavouri T, Semple J, Lehner B. Widespread conservation of genetic redundancy during a billion years of eukaryotic evolution. Trends in Genetics. 2008.  24(10):485-8.

Tischler JT, Lehner B, Fraser AG. Evolutionary plasticity of genetic interaction networks. Nature Genetics. 2008. Apr;40(4):390-1.

Lehner B. Selection to minimise noise in living systems and its implications for the evolution of gene expression. Molecular Systems Biology. 2008. 4:170.

Semple JI*, Vavouri T*, Lehner B. A simple principle concerning the robustness of protein complex activity to changes in gene expression. BMC Systems Biology. 2008. 2:1.

Lee I*, Lehner B*, Crombie C, Wong W, Fraser AG, Marcotte E. A single network comprising the majority of genes accurately predicts the phenotypic effects of gene perturbation in Caenorhabditis elegans. Nature Genetics. 2008. Feb;40(2):181-8.

Vavouri T, Walter K, Gilks WR, Lehner B*, Elgar E*. Parallel evolution of conserved noncoding elements that target a common set of developmental regulatory genes from worms to humans. Genome Biology. 2007 Feb 2;8(2):R15.

Lehner B, Crombie C, Tischler J, Fortunato A, Fraser AG. Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways. Nature Genetics. 2006 Aug;38(8):896-903.

Lehner B, Tischler J, Fraser AG. RNAi screens in C. elegans in a 96-well liquid format and their application to the systematic identification of genetic interactions. Nature Protocols. 2006 1(3):1617-1620.

Tischler J, Lehner B, Chen N, Fraser AG. Combinatorial RNA interference in C. elegans reveals that redundancy between gene duplicates can be maintained for more than 80 million years of evolution. Genome Biology. 2006 Aug 2;7(8):R69.

Lehner B, Calixto A, Crombie C, Tischler J, Fortunato A, Chalfie M, Fraser AG. Loss of LIN-35, the Caenorhabditis elegans ortholog of the tumor suppressor p105Rb, results in enhanced RNA interference. Genome Biology. 2006;7(1):R4

Lehner B and Fraser AG. A first-draft human protein-interaction map. Genome Biology. 2004;5(9):R63. Epub 2004 Aug 13.

Lehner B and Fraser AG. Protein domains enriched in mammalian tissue-specific or widely expressed genes. Trends in Genetics. 2004 Oct;20(10):468-72.
Lehner B and Sanderson CM. A protein interaction framework for human mRNA degradation. Genome Research. 2004 Jul;14(7):1315-23.

Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD and Sanderson CM.  Analysis of a high throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region. Genomics 2004 Jan;83(1):153-67.

Estevez AM, Lehner B, Sanderson CM, Ruppert T and Clayton C. The roles of inter-subunit interactions in exosome stability. Journal of Biological Chemistry. 2003 Sep 12;278(37):34943-51.

Lehner B, Williams G, Campbell RD and Sanderson CM. Antisense transcripts in the human genome. Trends in Genetics. 2002 Feb;18(2):63-5. 

Recent reviews

Lehner B, Park S.Cancer: Exploiting collateral damage. Nature. 2012 Aug 16;488(7411):284-5

Burga A, Lehner B. Beyond genotype to phenotype: why the phenotype of an individual cannot always be predicted from their genome sequence and the environment that they experience. FEBS J. 2012 Aug 30. doi: 10.1111/j.1742-4658.

Lehner B. Molecular mechanisms of epistasis within and between genes. Trends in Genetics. 2011 Aug;27(8):323-3

Lehner B, Kaneko K. Fluctuation and response in biology. Cell and Molecular Life Sciences. 2011 Mar;68(6):1005-10.

 

Vavouri T, Lehner B. Conserved noncoding elements and the evolution of animal body plans. Bioessays. 2009. Jul;31(7):727-35.

Lehner B, Lee I. Network-guided genetic screening: building, testing and using gene networks to predict gene function. Briefings in Functional Genomics and Proteomics. 2008 Apr 29.

Lehner B. Modelling genotype-phenotype relationships and human disease with genetic interaction networks. J Exp Biol 2007. 210(Pt 9):1559-66.

PDFs of some of these publications are available here.

Locations of visitors to this page

Selected Publications

Burga A, Casanueva MO, Lehner B..
Predicting mutation outcome from early stochastic variation in genetic interaction partners
Nature 480(7376):250-3. doi: 10.1038/nature10665 (2011).
Jelier R, Semple JI, Garcia-Verdugo R, Lehner B..
Predicting phenotypic variation in yeast from individual genome sequences
Nat Genet 43(12):1270-4. doi: 10.1038/ng.1007 (2011). abstract
Burga A, Lehner B..
Predicting phenotypic variation from genotypes, phenotypes and a combination of the two
Current Opinion in Biotechnology doi: 10.1016/j.copbio.2013.03.004 (2013). abstract
Lehner B.
Genotype to phenotype: lessons from model organisms for human genetics
Nature Reviews Genetics 14(3):168-78. doi: 10.1038/nrg3404 (2013). abstract
Andrew Fraser & Ben Lehner.
Systems Biology of Caenorhabditis elegans/ edited by Marian Walhout, Marc Vidal & Job Dekker
in Handbook of Systems Biology: Concepts and Insights Elsevier (2013).

 
Other information about the group
 
 

Group Members