Université de Strasbourg

Joseph Schacherer


Laboratory for Molecular Genetics, Genomics and Microbiology (GMGM), CNRS, University of Strasbourg

Joseph Schacherer, USIAS Fellow 2017

In 2005, Joseph Schacherer obtained a PhD in molecular and cellular biology from the Louis-Pasteur University in Strasbourg, France. Following the completion of his PhD, he joined the laboratory of Leonid Kruglyak at the Lewis Sigler institute of Integrative genomics at Princeton University (New Jersey, USA), where he began work on genomic approaches to study population genomics and intraspecies phenotypic variation. In 2007, he was appointed as assistant professor of genetics and genomics at the laboratory of Genetics, Genomics and Microbiology (UMR7156, University of Strasbourg - CNRS). In 2013, he became team-leader and brought together an experienced team of researchers with expertise in population genomics, genetics, bioinformatics and data analysis crucial to set up high-throughput sequencing and phenotyping experiments and analyse the data generated. The group’s long-term goal is to use population and functional genomics to have a better insight into the rules that govern the genotype-phenotype relationship within species.

Moreover, he was laureate of the National Institutes of Health (NIH) R01 grant program in collaboration with the Dunham group (Department of Genome Sciences, University of Seattle) twice, in 2012 and more recently in 2017. He also led the  1002 yeast genomes project. He was nominated member of the Institut Universitaire de France in 2016. And since September 2017, he is professor of genetics and genomics at the University of Strasbourg.

Project - Elucidating how traits are heritable through functional and population genomics across a whole subphylum

September 2017 - August 2019

Elucidating the causes of the awesome phenotypic diversity observed in natural populations is a major challenge in biology. It is now clear that the understanding of traits is not only hampered by non-heritable factors such as the environment and epigenetic variation, but also confounded by the lack of complete knowledge concerning the genetic components of complex traits. More than a century after the rediscovery of Mendel’s law, the genetic architecture of traits still resists generalization. In fact, dissection of the genotype-phenotype correlation in humans and other higher model eukaryotes such as Arabidopsis thaliana and Caenorhabditis elegans, while extremely important, is very difficult not only due to genetic complexity, pleiotropy and gene-environment interactions but also to large and complex genomes. This is increasingly evident as shown by recent genome-wide association studies, where identified causal loci explained relatively little of the heritability of most complex traits. Multiple justifications for this “missing heritability” have been suggested, including a large number of variants with small effects, rare variants, poorly detected structural variants and low power to estimate gene-gene interactions.

From this perspective, the budding yeast Saccharomyces cerevisiae is an attractive model system for understanding phenotypic diversity. In particular, its genome is physically small (12 Mb), genetically large (4,500 cM) and highly annotated. Natural populations harbour a decidedly broad phenotypic diversity, and a greater genetic variability than that found in humans. It is possible to precisely measure a large panel of phenotypes from the same population with ease, and the genetic basis of these phenotypes can be determined using different mapping strategies.

In this context, we will combine functional and population genomics approaches to (i) explore the genetic diversity among yeast isolates from various ecological niches of different non-conventional species, (ii) determine the recombination landscape within these species, and (iii) analyse the phenotype-genotype relationships. This comprehensive study will undoubtedly enlighten on the genetic origin of phenotypic diversity, the variation of the mutational and recombinational processes as well as their evolution. This project will undoubtedly represent a milestone in better understanding the general characteristics and evolution of the genetic architecture of complex traits.

Investissements d'Avenir