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Researchprojects of the Department of Biochemistry

Research

The research of the Deaprtment of Biochemistry centers in the fields of Molecular epigenetics, Protein/nucleic acid interaction and Synthetic biology.

In Molecular epigenetics, we study the methylation of DNA and histone proteins as well as protein domains that specifically read these modifications. We investigate the mechanism and specificiy of enzymes involved in epigenetic processes and are engaged in the development of enzyme inhibitors. In Synthetic biology, we aim to improve the properties of enzymes and proteins for various applications by rational and evolutionary design and develop artificial gene regulatory elements.

Current research projects of Prof. Jeltsch

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DNA methylation is an essential epigenetic modification involved in various biological processes. DNA methylation patterns are established in a largely unknown manner during the embryogenesis and development of mammals by the de novo DNA methyltransferases Dnmt3a and Dnmt3b. Dnmt1 methylates specifically hemimethylated CpG sequences after DNA replication, thereby copying DNA methylation patterns over cell divisions. We study the mechanism, regulation, and conformational transitions of human DNA methyltransferases in vitro and in cells. The aim of this project is to understand how DNA methyltransferases can fulfill their central cellular functions. Moreover, we devolp artifical, DNA methylaiton based epigenetic gene regulatory networks in bacteria for the memory and processing of external signals.

 

DNA methylation is an essential epigenetic modification involved in various biological processes. DNA methylation patterns are established in a largely unknown manner during the embryogenesis and development of mammals by the de novo DNA methyltransferases Dnmt3a and Dnmt3b. Dnmt1 methylates specifically hemimethylated CpG sequences after DNA replication, thereby copying DNA methylation patterns over cell divisions. We study the mechanism, regulation, and conformational transitions of human DNA methyltransferases in vitro and in cells. The aim of this project is to understand how DNA methyltransferases can fulfill their central cellular functions. Moreover, we devolp artifical, DNA methylaiton based epigenetic gene regulatory networks in bacteria for the memory and processing of external signals. 

Post-translational modifications (PTMs) of N-terminal histone peptides play an important role in gene regulation and in the regulation of the state of chromatin. The biological effect of these PTMs is essentially mediated by protein interaction domains which bind PTM specifically to target proteins. The aim of this project is to identify and investigate binding domains for lysine methylation in histone and non-histone proteins. We plan to systematically clone and purify candidate domains and to investigate their interaction with modified histone peptides and with randomized peptides. We also develop binding domains for biotechnological applications and we apply reading domains to detect DNA methylation and histone modifications at genomic target loci in live cells.

In this project we investigate the enzymatic properties of Dnmts and PKMTs which contain cancer-mutations. Our results will help to define the carcinogenic effect of Dnmt and PKMT mutations observed in tumors and to understand how changes in DNA and protein methylation lead to cancer. This will support the development of more targeted therapies for tumors containing mutated Dnmts and PKMTs. 

In this project, we are developing systems for epigenome editing that allow epigenetic modifications to be targeted at defined genomic loci. We employ chimeric enzymes in which artificial DNA recognition domains, e.g. Zinc finger proteins, TALs, or CRIPSR / Cas9 complexes for locus-specific DNA binding are fused to chromatin-modifying enzymes (such as DNA methyltransferases or lysine methyltransferases). We use Epigenom editing, in order to silence oncogenes in tumor cells or to correct epigenetic modifications in cells with imprinting defect. In addition, we study the changes of histone and DNA modifications to natural chromatin after the introduction of one or more defined modifications to better understand the process of reprogramming.

Current projects of Dr. Philipp Rathert

A central question of epigenome reserch is how chromatin or DNA binding proteins interact with one another to switch genes on or off at the right time point to establish and maintain a healthy cellular state. The project investigates the dynamics and wiring of chromatin regulators, as well as the induced transcriptional output under different conditions using state-of-the-art functional genetic tools (RNAi or CRISPR/Cas9) with cell biology and biochemical assays. 

EU Marie Sklodowska-Curie Projekt by Frau Dr. Rawluszko-Wieczorek

Lysine methylation marks manifest their biological effect via so-called ‘readers’ (or reading domains) which recognize and bind the methylation mark and induce biological responses. Reading domains include Plant homeodomains (PHD) and Chromodomains (CD) found in many chromatin proteins. KMET-READ investigates the biological role of these reading domains in essential histone lysine methyltransferases - PHDs in MLL2 and MLL3 and CDs in SUV39H1 and SUV39H2, and aims to discover novel reading domains.

 Link to project page

Current research projects of Prof. Wolf

The work of Prof. Wolf is concerned with the ubiquitin-proteasome-system induced cellular regulation and protein homeostasis. Research focusses on the regulation of the central carbohydrate pathways glycolysis and gluconeogenesis as well as on protein quality control and the degradation of misfolded proteins. The studies on the model yeast unravel basics for our  undertanding of  a variety of human diseases. Current projects deal with the glucose induced regulation of glycolysis and gluconeogenesis and ubiquitin-proteasome catalyzed catabolite degradation of gluconeogenic enzymes as well as with protein quality control and elimination of misfolded proteins of the cellular cytoplasm as well as of the secretory pathway (ER-associated protein degradation).

Kontakt

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Prof. Dr.

Albert Jeltsch

Chair

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Dr.

Philipp Rathert

group leader

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Prof. Dr.

Dieter H. Wolf

former chair