Members

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, Aaron New, Xianghua (Cici) Li, Andre Faure, Guillaume Diss, Benedetta Bolognesi

PhD Students:

Adam Klosin, Kadri Reis, Marcos Pérez, Júlia Domingo, Pablo Baeza

Technician:

Cristina Hidalgo

Selected Publications

Supek F, Lehner B.
“Differential DNA mismatch repair underlies mutation rate variation across the human genome.”
Nature, 521:81-4 (2015).

Park S, Lehner B.
“Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types.”
Mol Syst Biol, 11(7):824 (2015).

Krüger AV, Jelier R, Dzyubachyk O, Zimmerman T, Meijering E, Lehner B.
“Comprehensive single cell-resolution analysis of the role of chromatin regulators in early C. elegans embryogenesis.”
Dev Biol, 398(2):153-62 (2015).

Van Dijk D, Dhar R, Missarova AM, Espinar L, Blevins WR, Lehner B, Carey LB.
“Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage.”
Nature Commun, 6:7972 (2015).

Toufighi K, Yang JS, Luis NM, Aznar Benitah S*, Lehner B*, Serrano L*, Kiel C*.
“Dissecting the calcium-induced differentiation of human primary keratinocytes stem cells by integrative and structural network analyses.”
PLoS Comput Biol, 11(5):e1004256 (2015).

Francesconi M, Lehner B.
“Reconstructing and analysing cellular states, space and time from gene expression profiles of many cells and single cells.”
Mol Biosyst, 11(10):2690-8 (2015).

New AM, Lehner B.
“Systems biology: Network evolution hinges on history.”
Nature, 523(7560):297-8 (2015).

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

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. We have shown that how mutations in different genes interact to cause cancer changes across different cell types (Park 2015) and that DNA mismatch repair varies in efficiency across the human genome resulting in elevated somatic mutation rates in late replicating heterochromatic regions (Supek 2015). In addition, we are undertaking a large-scale analysis of the contribution of rare germline variants to human cancers.

Genetic variation: we are using deep mutation scanning to systematically and comprehensively analyse the effects of genetic variation on a range of simple and more complicated biological functions (genotype-to-phenotype landscapes). We are continuing to work on the mechanisms that cause dosage-sensitivity.

Epigenetics: we have discovered a model system for studying long-term transgenerational epigenetic inheritance in C. elegans and are using it to dissect the molecular mechanisms underlying the inheritance and resetting of epigenetic information between generations. In addition, we are studying how impaired DNA replication results in altered epigenetic inheritance. We are studying the molecular mechanisms underlying examples of how the environment experienced in one generation or early in life can influence traits in the next generation and as adults. Finally, we are dissecting the causes of cell-to-cell variation in gene expression in mammalian stem cells and the causes of cell-to-cell variation in growth rates in yeast.

Selected Publications

Supek F, Lehner B.
“Differential DNA mismatch repair underlies mutation rate variation across the human genome.”
Nature, 521:81-4 (2015).

Park S, Lehner B.
“Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types.”
Mol Syst Biol, 11(7):824 (2015).

Francesconi M, Lehner B.
“Reconstructing and analysing cellular states, space and time from gene expression profiles of many cells and single cells.”
Mol Biosyst, 11(10):2690-8 (2015).

New AM, Lehner B.
“Systems biology: Network evolution hinges on history.”
Nature, 523(7560):297-8 (2015).