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Elucidating the pathomechanism of chromosomal rearrangements in fibroblasts from patients by investigating enhancer–promoter specificity.

Max Planck Institute for Molecular Genetics





About Blanka

Read about Blanka’s project.



Stefan Mundlos
MPIMG, 1st Supervisor

Giacomo Cavalli
CNRS, 2nd Supervisor


Despite new sequencing technologies and other methods of genome analysis, congenital malformations remain without a molecular diagnosis in a majority of individuals. The aim of this project is to increase the number of diagnosable cases. This will be achieved by first using novel technologies (HiC) for the detection of structural variants and abnormal chromatin interactions in fibroblasts from patients and further followed by investigating mechanisms underlying pathogenicity of those structural variants.


While growing fibroblasts from patients with congenital malformations, cells will be subjected to HiC analysis to investigate their genome-wide interaction profile. To determine the variability of HiC in fibroblasts samples HiC will be performed in a sufficient number of control cell lines. The data will be bioinformatically analyzed and particular loci modeled together with WP4. Data will be compared. Variants will be identified based on the whole-genome sequencing of patient samples. To elucidate mechanisms causing pathogenicity of detected structural variants high-throughput genome engineering will be employed in mouse embryonic stem cells to analyze enhancer-promoter interaction specificity. Detected abnormalities that are considered potentially pathogenic will be tested in mouse models.

Expected Results

A new dimension of analysis that will be able to detect structural variants at unprecedented sensitivity and accuracy. In addition, detection of abnormal chromatin interactions either due to structural variants or other causes that may explain the disease.

Planned Secondments

CNAG-CRG, Spain (6 months):
Data analysis and modelling.
CNRS, France (3 months):
HiC improvement.

Enrolment in doctoral programs

PhD in Biology for the Freie Universität Berlin (FU)


Kragesteen BK, Spielmann M, Paliou C, Heinrich V, Schöpflin R, Esposito A, Annunziatella C, Bianco S, Chiariello AM, Jerković I, Harabula I, Guckelberger P, Pechstein M, Wittler L, Chan WL, Franke M, Lupiáñez DG, Kraft K, Timmermann B, Vingron M, Visel A, Nicodemi M, Mundlos S, Andrey G. Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis. Nat Genet. 2018 Oct;50(10):1463-1473.

Spielmann M, Lupiáñez DG, Mundlos S. Structural variation in the 3D genome. Nat Rev Genet. 2018 Jul;19(7):453-467.

Bianco S, Lupiáñez DG, Chiariello AM, Annunziatella C, Kraft K, Schöpflin R, Wittler L, Andrey G, Vingron M, Pombo A, Mundlos S, Nicodemi M. Polymer physics predicts the effects of structural variants on chromatin architecture. Nat Genet. 2018 May;50(5):662-667.