Finalist EPFL doctorate Award 2015 – Sebastian Waszak
Special distinction from the selection committee to Sebastian Waszak for his thesis "A systems approach to elucidate the genetic architecture of molecular phenotypes". Thesis n° 6179 (2014). Thesis director: Prof. B. Deplancke
It is becoming increasingly recognized that variation in non-coding DNA sequences is in large part responsible for variation in complex organismal phenotypes. However, the relationship between non-coding DNA variation and phenotypic variation remains obscure as we currently have a poor understanding of how DNA variation affects molecular phenotypes such as gene expression and protein-DNA interactions. This thesis therefore focused on decoding metazoan gene regulatory networks that mediate gene expression using a novel systems approach that integrates, respectively, chemical and genetic perturbations with genome-wide molecular measurements (i.e., gene expression, protein-DNA interactions, and histone modifications). The primary contributions of this thesis are (i) a genome-wide map of gene regulatory DNA sequences in wild-derived strains of Drosophila melanogaster, (ii) novel cis and trans regulatory components in the murine adipogenic gene regulatory network, (iii) a computational method that identifies technical artifacts in the context of epigenomic associations, (iv) and genetic associations with variable molecular phenotypes (e.g., protein-DNA interactions) at gene regulatory DNA sequences in a human population.
Figure 1. Transmission of protein-DNA interactions from parents to offspring.