Systems Biology

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Genetic Systems

This group is part of the EMBL/CRG Research Unit in Systems Biology

GROUP LEADER:
Ben Lehner (ICREA Research Professor and AXA Professor of Risk prediction in age-related diseases)
POSTDOCTORAL RESEARCHERS:
Mirko Francesconi, Solip Park, Fran Supek, Riddhiman Dhar, Philippe Julien, Aaron New, Xianghua (Cici) Li, Andre Faure, Guillaume Diss, Benedetta Bolognesi (joint with Tartaglia lab)
PhD STUDENTS:
Adam Klosin, Kadri Reis, Marcos Pérez
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, and we use large-scale experiments, small-scale experiments and computational analyses.

 


Research Projects

  • Epigenetic variation: We are studying the causes of phenotypic variation amongst isogenic individuals using yeast and worms as model systems.
  • 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. During the past year our main contribution was to demonstrate that ‘silent’ synonymous somatic mutations are frequently selected and so causally important in human cancers, with one effect being alterations in the splicing of oncogenes. This work was a collaboration with the labs of Toni Gabaldón and Juan Valcárcel
  • Phenotypic robustness: We are studying the mechanisms that confer phenotypic robustness during development, in particular to mechanical perturbations and gene expression fluctuations.
  • Inherited genetic variation: We are currently studying the effects of inherited genetic variation on dynamic processes (e.g. Francesconi and Lehner, Nature 2014) and we are using massively parallel libraries and selection to comprehensively analyse the effects of genetic variation on a range of simple biological functions.

Selected Publications

Francesconi M, Lehner B.
“The effects of genetic variation on gene expression dynamics during development.”
Nature, 505:208-11 (2014).

Supek F, Minana B, Valcarcel J, Gabaldon T, Lehner B.
“Synonymous mutations frequently act as driver mutations in human cancers.”
Cell, 156:1324-1335 (2014).

Barberán-Soler S, Fontrodona L, Ribó A, Lamm AT, Iannone C, Cerón J, Lehner B*, Valcárcel J*
“Co-option of the piRNA pathway for germline-specific alternative splicing of C. elegans TOR.”
Cell Rep, 8(6):1609-16 (2014).

Supek F*, Lehner B*, Hajkova P*, Warnecke T.
“Hydroxymethylated cytosines are associated with elevated C to G transversion rates.”
PLoS Genet, 10(9):e1004585 (2014).

Kri Ko A, Copi T, Gabaldón T, Lehner B, Supek F.
“Inferring gene function from evolutionary change in signatures of translation efficiency.”
Genome Biol, 15(3):R44 (2014).

Semple JI, Lehner B.
“Single and dual drug selection for transgenes following bombardment of Caenorhabditis species.”
Methods, pii: S1046-2023(14)00185-6 (2014).