Systems Biology

ben-lehner
Genetic Systems

Group Structure

This group is part of the EMBL/CRG Research Unit in Systems Biology
GROUP LEADER:
Ben Lehner (ICREA Research Professor)
POSTDOCTORAL RESEARCHERS:
Mirko Francesconi, Solip Park, Fran Supek, Riddhiman Dhar, Jasna Lalic, Philippe Julien, Aaron New, Benedetta Bolognesi (joint with Tartaglia lab)
PhD STUDENTS:
Adam Klosin, Kadri Reis, Marcos Pérez, Kiana Toufighi (joint with Serrano lab)
TECHNICIAN:
Cristina Hidalgo

Summary

We study the causes of phenotypic variation amongst individuals, including the distribution and effects of inherited genetic variation, epigenetic variation (environmental, stochastic, inherited), and germline and somatic mutations.  As model systems we use yeast, worms and tumours.  We use both experimental and computational approaches.


Research Projects

  • Inherited genetic variation: We have developed an efficient experimental design to study the effects of inherited genetic variation on dynamic processes and have applied this to the genetic analysis of gene expression dynamics during 12 hours of the development of C. elegans (Francesconi and Lehner, Nature 2014).  We are also studying how mutations interact within and between loci to cause phenotypic variation (epistasis).
  • Epigenetic variation: We are studying the causes of early variation in gene expression amongst isogenic individuals that is important for inter-individual phenotypic variation.  We are also studying the impact of epigenetic variation on sequence evolution and vice versa (Warnecke et al. PLoS Comput Biol 2013) and the impact of epigenetic variation on the evolution of gene expression (Park and Lehner, Mol Sys Biol 2013).
  • Somatic mutations: Somatic mutations are an intriguing example of how stochastic processes influence phenotypic variation amongst individuals, for example being the main cause of cancer.  We are studying somatic mutation processes, the types of mutations that contribute to cancer, their effects on gene expression and how these mutations interact.
  • Phenotypic robustness: We are studying the mechanisms that confer phenotypic robustness during development, in particular to mechanical perturbations and gene expression fluctuations.

Selected Publications

  1. Francesconi M, Lehner B.
    “The effects of genetic variation on gene expression dynamics during development.”
    Nature, doi: 10.1038/nature12772. Epub 2013 Nov 24.
  2. Lehner B.
    “Genotype to phenotype: lessons from model organisms for human genetics.”
    Nature Reviews Genetics, 14:168-78 (2013).
  3. Park S, Lehner B.
    “Epigenetic epistatic interactions constrain the evolution of gene expression.”
    Molecular Systems Biology, 9:645 (2013).
  4. Warnecke T, Becker EA, Facciotti MT, Nislow C, Lehner B.
    “Conserved substitution patterns around nucleosome footprints in eukaryotes and Archaea derive from frequent nucleosome repositioning through evolution.”
    PLoS Comput Biol, 9:e1003373 (2013).
  5. Janich P, Toufighi K, Solanas G, Luis NM, Minkwitz S, Serrano L*, Lehner B*, Benitah SA*.
    “Human epidermal stem cell function is regulated by circadian oscillations.”
    Cell Stem Cell, 13:745-53 (2013).
  6. Burga A, Lehner B.
    “Predicting phenotypic variation from genotypes, phenotypes and a combination of the two.”
    Current Opinion in Biotechnology, 24(4):803-9 (2013).