A primary goal in biology is to understand the molecu lar basis of phenotypic evolution, most notably that of humans and other mammals. Most phenotypic differences between species are likely due to regulatory mutations that affect gene expression. Our lab has therefore previously generated comprehensive sets of RNA-seq data and various other high-throughput “omics” (e.g., epigenomic, metabolomic, proteomic) datasets for a large collection of tissues from representative mammals and performed integrated analyses of these data to study the expression (regulatory) evolution of mammalian genomes across gene types, lineages, organs, developmental stages, chromosomes and sexes (see e.g. Brawand et al. Nature 2011, Necsulea et al. Nature 2014, Cortez et al. Nature 2014; selected publications are listed below). In the framework of a new line of research, our lab aims to move from the bulk tissue level to that of individual cells and thus illuminate how evolutionary changes in cellular composition and underlying gene regulatory networks have led to the emergence of species- or lineage-specific organ anatomies and functions. The first aim in this PhD project is to develop and apply single-cell sequencing protocols for profiling transcriptomes and epigenomes across various tissues and developmental stages from selected mammalian species. The second major goal, which will be based on results from the first aim, is to utilize cellular systems (derived from different species and tissues) in conjunction with genome engineering techniques to identify key regulatory mutations that underlie the evolution of distinct cellular phenotypes. For more information about our lab and project see our webpage (http://www.zmbh.uni-heidelberg.de/Kaessmann/default.shtml ) or contact Prof. Henrik Kaessmann (Henrik.Kaessmann@zmbh.uni-heidelberg.de).
Selected publications:
Cortez, D., Marin, R., Toledo-Flores, D., Froidevaux, L., Liechti, A., Waters, P.D., Grutzner, F., and Kaessmann, H. (2014) Origins and functional evolution of Y chromosomes across mammals. Nature 508: 488-493.
Necsulea, A., Soumillon, M., Warnefors, M., Liechti, A., Daish, T., Zeller, U., Baker, J.C., Grutzner, F., and Kaessmann, H. (2014) The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505: 635-640.
Necsulea, A. and Kaessmann, H. (2014) Evolutionary dynamics of coding and noncoding transcriptomes. Nat. Rev. Genet. 5: 734-48.
Brawand, D., Soumillon, M., Necsulea, A., Julien, P., Csardi, G., Harrigan, P., Weier, M., Liechti, A., Aximu-Petri, A., Kircher, M., Albert, F.W., Zeller, U., Khaitovich, P., Grutzner, F., Bergmann, S., Nielsen, R., Paabo, S., and Kaessmann, H. (2011) The evolution of gene expression levels in mammalian organs. Nature 478: 343-348.
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