Computational Genomics

Dr. Helene Kretzmer

We are a computational group seeking to understand the role of the epigenome and its key regulators as core drivers of development and disease. We tackle biological questions computationally and work closely with experimental and clinical scientists. Our main focus is on the integration of multiple forms of next-generation sequencing data, including large single-cell, epigenomic and long-read Nanopore data, to better understand how genome regulation changes to support various developmental processes or malignant diseases. We work closely with several labs at the institute, especially the lab of Alexander Meissner and are also open to creative, collaborative project ideas with other labs. We strongly support an interdisciplinary, supportive and friendly work environment and are looking for a highly motivated computational PhD student with a firm interest in epigenetic regulation.

 

Epigenetic control and nuclear function of repetitive DNA in B cell differentiation and malignant transformation

B cell differentiation from precursor cells to mature plasma cells is directed by epigenetic changes and heavy reprogramming of DNA methylation at the germinal center states. Previous studies have defined the order of epigenetic changes during physiologic B cell differentiation as well as the landscape of epigenomic changes during B cell transformation leading to lymphomagenesis, which intriguingly includes the acquisition of a cancer-like DNA methylation landscape.

Nevertheless, due to technical limitations and restrictions of the human reference genome, epigenetic alterations occurring at repetitive sequences remain largely understudied. This results in a major lack of knowledge as repetitive sequences are key to physiologic processes in B-cell (e.g., IG switch recombination, telomere maintenance) as well as lymphomagenesis (e.g., numerical and structural chromosome alterations).

This project aims to systematically close this gap and discover the rules for epigenetic regulation within the B cell lineage, including integrative analysis of a large cohort of next-generation sequencing data.  Moreover, we seek to incorporate novel long-read sequencing data from normal B cells and B cell lymphomas in the light of the recently completed T2T genome. In particular, we are interested in understanding the change in regulation across large repetitive domains within the genome, such as centromeric regions, that have critical biological functions but remain extraordinary hard to analyze with short-read sequencing data. The project will be developed in close collaboration with our partners in the group of Prof. Siebert (Ulm University Hospital) and seeks to create a true “genome-scale” picture of this developmental process, including the relationship of these elements to the onset of multiple forms of lymphoma.

For more information visit the website of the Computational Genomics Group.