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Nov 17, 2022

Seminar (2022-11-17)

School of Biomedical Sciences is pleased to invite you to join the following seminar:

Date: Thursday, 17 November, 2022
Time: 5:00 pm – 6:30 pm

Zoom Link:
Meeting ID: 952 7214 4054
Password: 768868

Speaker: Professor Stefan Mundlos, External Scientific Member and Research Group Leader, Max Planck Institute for Molecular Genetics
Title: Variants in the non-coding genome and how they affect phenotype - lessons from development, disease, and evolution




Stefan Mundlos studied Medicine at the University of Göttingen, the University of California San Diego (UCSD), the University of Marburg, at the Walter and Eliza Hall Institute in Melbourne, and at the University of Heidelberg. He completed a clinical training in Pediatrics and Human Genetics at the University Hospital of Mainz, Germany. Thereafter, he spent one year as a research fellow at the Murdoch Institute for Research into Birth Defects in Melbourne, Australia, followed by a postdoc period at the Department of Cell Biology in Harvard, Boston, USA. He received his habilitation 1997 back in Mainz. In 1999 he was nominated for a Professorship in Human Genetics in Heidelberg. In 2000 he moved to Berlin. He is Director of the Institute for Medical and Human Genetics at the Charité and group leader of the Research Group Development & Disease at the Max Planck Institute for Molecular Genetics. The main focus of his research is in understanding genetic mechanisms of normal and abnormal development with a particular focus on the skeleton. Mechanisms of gene regulation and how they are influenced by genomic variation are an important aspect of his current work.



Although 98% of the human genome are non-coding, very few disease-causing mutations have been reported that are not coding. In part, this is due to the fact that variants in the non-coding genome are difficult to interpret because of our limited knowledge how variations in sequence or sequence structure can affect gene expression. Recent studies have shown that the genome is organized in a specific three-dimensional (3D) configuration which has a major influence on gene regulation. Studies using chromosome conformation capture technologies such as HiC have shown that mammalian genomes are organized in distinctly folded chromatin modules, called topologically associated domains (TADs) that are separated from each other by boundary regions. TADs subdivide the genome into discrete genomic units that restrict the possible contacts enhancers can establish with their target genes. We use a CRISPR/Cas9 based strategy to investigate the effect of variations in this configuration in vivo in mice. Deletions, duplications and inversions, for example, can result in the fusion of TADs and the re-wiring of enhancer-promoter contacts and consecutive alterations in gene expression. Such changes can cause disease by gene misexpression (Lupianez et al. 2015), but can also be the origin of evolutionary novelty, as shown by us for the mole (Real et al. 2020). Thus, alterations in the 3D chromatin configuration can result in major shifts of gene expression. In an evolutionary context such changes in TAD-landscapes need to be incorporated in the existing regulatory context (Ringel et al. 2022). Our findings provide a framework for interpreting the effect of structural variations in a disease and evolutionary context.


Should you have any enquiries, please feel free to contact Miss Angela Wong at 3917 9216.