Now accepting applications from 01 June till 15 July 2017!

All eligible candidates must fulfill the formal requirements outlined in the application procedure. Here you can find a specification of our application projects (alphabetically listed by the name of the group leader):

3D-Structure in Molecular Fragment Mining - Christian Borgelt & Michael Berthold / Computational Life Science

The project focuses on the inclusion of the configuration (stereoisomerism) and conformation (binding and rotation/torsion angles) into molecular fragment mining in the form of frequent subgraph mining in molecular databases. While this is fairly straightforward for the configuration of molecules, by enhancing the graph representation with special vertex attributes, the conformation of (bio)molecules has been taken into account mainly by re-representing the molecules in structures other than graphs. Enhanced graph representations capturing molecule conformation face the challenge of having to allow for approximate matching, which renders the search space no longer easily separable, thus requiring special techniques to avoid duplicate results and ensure efficient search. However, such a approach will provide new technology for linking conformational changes of biomolecules that occur in different situations and environments.

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Identification of endogenous LRH-1 ligands - Thomas Brunner / Biomedicine

Liver Receptor Homolog-1 (LRH-1/NR5a2) is a nuclear receptor and transcription factor with broad activities in the regulation of development, steroidogenesis, metabolism, tissue regeneration and cancer. LRH-1 is considered an orphan nuclear receptor as no endogenous ligands are currently known. Various studies have however shown that certain chemicals and especially phospholipids can bind to the ligand binding pocket of LRH-1, and alter its transcriptional activity. Moreover, phospholipid ligands also demonstrate in vivo therapeutic activities in the regulation of LRH-1-dependent pathologies in mouse models, e.g. type 2 diabetes.

In our ongoing research we successfully identified LRH-1 ligands derived from probiotic bacteria. In this specific project we aim at identifying cell-autonomous endogenous ligands from human or mouse cells, and tissues using established extraction, purification and identification strategies. Upon identification we will assess the organ and tissue distribution of endogenous LRH-1 ligands, and monitor their dynamic during the pathogenesis of metabolic and inflammatory diseases. Furthermore, we will model ligand-LRH-1 interactions in order to optimize LRH-1 ligands by synthetic organic chemistry. Optimized synthetic homologs of endogenous ligands will then be tested for their therapeutic action in various in vitro and in vivo disease model systems.

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Functional anisotropic nanopartices templated by designer proteins - Helmut Cölfen / Biophysics

Proteins with nanopockets shall be used for the genetical modification with unnatural amino acids, the or-thogonally functionalizable amino acids cysteine or charged amino acids at defined positions in the protein pocket. That way, a highly functionalized and spatially defined nanopocket shall be designed which shall be specifically used for ion accumulation and subsequent nucleation of a cluster of a functional nanomaterial like metals or semiconductors. By this strategy, the dimensions and the nucleation cluster shall be highly controlled and thus, nanostructural systems with new properties und functions be accessible.

The project seeks for a candidate with solid background in nanoscience and the chemistry of nanomaterials and a great interest in protein engineering.

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De novo synthesis of aristolochic acid derivatives and their toxicities - Daniel Dietrich / Biomedicine

Aristolochic acid (AA) is a food contaminant and component of traditional Chinese medicine, and induces nephropathy as well as urothelial cancer in humans. AA is metabolized in the liver and putatively also in the kidney as major target organ. However, the individual toxicologically relevant kinetics and activities of the AA metabolites in human kidney and bladder cells are unknown to date. To elucidate the latter we plan to de novo synthesize a number of AA derivatives incl. the highly active aristolactam-I (ALI) with various markers. By applying these AA derivatives to cultures of a human renal epithelial cell line (RPTEC) as well as urothelial HU1 cells, we want to investigate the uptake and excretion kinetics as well as their toxicologically relevant interaction with subcellular targets (incl. mitochondrial impairment, protein and DNA adducts) and apical responses e.g. cell death (necrosis, apoptosis) and transcriptome changes. For facilitated monitoring of the distribution of AA derivatives using life-cell imaging, we will couple the derivatives to fluorophores, albeit being conscious that this could affect the kinetic and dynamic behavior of the individual derivatives. By this approach, we will be able to follow the uptake and the potential subcellular accumulation of AA derivatives, as well as, in conjunction with the transcriptome analysis, to provide an in-depth understanding of the downstream effects of AA derivatives in the different cell types.

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Multiply-addressable nano-structural probes - Malte Drescher / Biophysics

In our group, we develop and apply spectroscopic methods in order to determine structure and dynamics of bio-macromolecules in complex environments. In this project, we will develop an approach by combining optical and EPR excitation and corresponding site-directed labelling strategies. An ideal candidate for the project could be a chemist with a strong interest in physical chemistry, a biologist with a strong interest in physical characterization methods, or a physicist with a strong interest in biophysics.

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Biological and biophysical characterization of substrate engagement mechanisms by NAC - Martin Gamerdinger / Cellular Biochemistry

The conserved nascent polypeptide-associated complex (NAC) is a ribosome-associated chaperone that takes a leading role in guiding proteins to their native state and final destination. Despite playing an essential role for maintaining protein homeostasis, little is known about how NAC engages its substrates. The major goal of this project is to elucidate the substrate binding characteristics of NAC at atomic resolution by combining biological in vivo experiments using C. elegans as a model system with biophysical NMR approaches performed in vitro.

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The mechanisms of pseudo-biomineralization - Dr. Denis Gebauer / Cellular Biochemistry

Bacteria can passively and actively interact with forming calcium carbonate minerals, and thereby alter their structure. In some cases, the level of control is finely regulated to form features that are highly reminiscent of shells. In this project, we will elucidate the underlying biochemical and physicochemical mechanism allowing bacteria to achieve this kind of "pseudo-biomineralization". The short-term goal is to understand its genetic, proteomic and metabolic basis, and the physicochemical means that allow influencing calcium carbonate formation in specific ways. The long-term vision is that the process of pseudo-biomineralization can be actively controlled and bacteria can be employed to generate, or repair, mineral-based materials such as concrete with a high level of control and fidelity. This could be achieved on length scales that are otherwise difficult to realize via bottom-up strategies, e.g., resulting in nanostructured concrete with drastically improved material properties.

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Bacterial Glutarate Oxidation and its Role in Central Carbon and Energy Metabolism - Jörg Hartig & David Schleheck / Cellular Biochemistry

We are looking for a highly motivated PhD candidate with research experience in microbiology and/or biochemistry, in order to carry out research at the intersection of biology, chemistry, and computer sciences. The groups of Jörg Hartig and David Schleheck, and the Falk Schreiber group, will team up in order to investigate a novel route in the central carbon and energy metabolism of bacteria. The physiological role of the reactions will be investigated with interdisciplinary approaches including microbiology, chemical biology, and metabolic modeling.

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High throughput mapping of stress-response pathways in neuronal cells - Marcel Leist / Biomedicine

We want to identify prediction models that use changes in biological networks to indicate (ii) toxicity of chemicals (altered cell phenotype) and (ii) their potential targets (disturbed protein activity or regulatory module). For this purpose, we use as model system human neurons, differentiated from pluripotent stem cells. Network changes are recorded on the level of transcriptome changes, and alterations of energy and central carbon metabolism after exposure of cells to neurotoxicants. In the past we used measures of overall network changes for prediction models. In this project, we want to identify individual regulatory subnetworks that are activated by chemical stressors, and we intend to define the extent to which such networks can be deregulated without compromising overall cell survival. We also want to explore whether similar information can be derived by methods that allow a higher throughput. For this purpose, we have selected master stress response genes that cover a wide spectrum of toxicant responses. The GFP-based reporter constructs are integrated in pluripotent cells and activation of stress responses networks may thus be monitored at high throughput in neuronal populations to generate data for toxicant prediction models.

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ChemoBioengineering of hybrid proteo-silica matrices for three-dimensional cell culturing - Olga Mayans / Biophysics

There is a strong demand for synthetic 3D extracellular matrix mimetics that can imitate the native cellular microenvironments of the human body. By supporting propagation and lineage-specific cell differentiation in near-native conditions, such matrices would permit reproducing the early developmental stage of tissues and organs ex vivo. This has crucial applications in developmental biology, toxicology and regenerative medicine. By combining self-assembling proteins and gel-forming organo compounds, this projects aims to develop a novel hybrid matrix with improved mechanical, chemical, and bioreactive features to serve as a 3D substrate in cell culture.

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Immersive analytics of molecular dynamics simulations - Falk Schreiber / Computational Life Science

Molecular dynamics simulations (MDS) are important to understand biomolecular systems and materials. MDS produce large amounts of complex data representing spatial and/or temporal changes. To understand MDS results tasks such as analysing single simulations, comparing simulation runs, classifying molecular structures, capturing interesting events, finding outliers, aggregating data etc. are highly important. Current methods do not support such tasks well and no current tool integrates the full analysis workflow. The aim of this project is therefore to apply and further develop immersive analytics methodology and to implement an integrated tool that allows to perform the workflow interactively in the same environment (including rerunning or adapting simulations). Research challenges are the development of novel visualisation and interaction methods in immersive environments as well as the development of metrics and methods for the temporal and structural aggregation of data and structures.

We are looking for a highly motivated PhD candidate with a strong computer science background in order to carry out research at the intersection of chemistry, biology, and computer science. The groups of Ch. Peter and F. Schreiber will team up in order to develop novel immersive analytics methods to explore and analyse molecular dynamics simulation data.

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Studying protein networks by unnatural amino acid technology and structural proteomics - Florian Stengel / Cellular Biochemistry

The aim of this this project is to use unnatural amino acid technology and structural proteomics to address the functional and structural relevance of selected posttranslational modifications for protein-protein interactions.

Mass spectrometry (MS) has been at the forefront in our quest to detect and measure posttranslational modifications (PTMs) of proteins. However, studying the exact effect of this modification on the level of the intact protein complex and the wider protein-protein interaction network are technically very challenging and thus remain largely unknown.

In order to do so, we will use the unnatural amino acid technology to fabricate proteins that contain specific bio-orthogonal, non-hydrolyzable PTMs and structural proteomics and mass spectrometry to probe structural and conformational changes of protein-protein interactions induced by a specific PTM.

Candidates should have a solid training in chemistry, biochemistry or life science and should be eager to combine organic chemistry with mass spectrometry.

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Synthesis and Biological Function of Microcystins - Valentin Wittmann / Synthetic Chemistry

Microcystins (MCs) are cyclic heptapeptides that are produced by cyanobacteria. They can be released to the water during harmful algal blooms and are a serious threat to animals and humans. Although the first publication on MC research dates back to 1878, their physiological function in cyanobacteria is still under scientific debate. In previous investigations we developed the first isomerization-free total synthesis of MCs in solution (J. Org. Chem. 2017, 82, 3680), we synthesized MC analogs with an unprecedented selectivity for inhibition of protein phosphatase (PP)2A over PP1 (Angew. Chem., Int. Ed. 2016, 55, 13985), and we developed a method for the regioselective cleavage of covalent MC-protein conjugates for improved MC analytics in biological samples (Chem. Eur. J. 2016, 22, 10990). In the current project, we will develop syntheses of tailored MC derivatives for subsequent biological studies. In cooperation with Prof. Daniel Dietrich (Biology Department) we will search for MC interaction partners and study MC transport by organic anion transporting peptides (OATPs).

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Visualization of protein PARylation in live cells - Andreas Zumbusch / Biophysics

Post-translational modification of proteins by covalent and non-covalent attachment of small chemical groups is important for the regulation of protein activity and function. The visualization of the modification status of target proteins promises to give important insight into the influence of specific modifications. The aim of this project is to implement a technique which allows the optical imaging of protein poly-ADP-ribose(PAR)ylation in living cells.

PARylation is a protein modification which plays an important role in DNA repair mechanisms. It consists in the enzymatic transfer of an ADP-ribose unit from nicotinamide adenine dinucleotide (NAD) onto a protein. This can lead to the formation of poly-ADP-ribose chains on the protein substrate. The proposed approach to visualize protein PARylation relies on a close collaboration with groups in the chemistry and the biology department. It is based on combining the chemical modification of NAD with novel optical microscopy approaches. Initially, a combined setup for photoinduced DNA damage and fluorescence lifetime imaging microscopy (FLIM) of live cells will be established. Fluorophore modified NAD analogues, which have previously been shown to be enzymatically processed, will then be used to form fluorophore tagged PAR chains on different proteins involved in DNA repair. Protein specificity is achieved by GFP tagging of the proteins of interest. The modification status of the latter shall be monitored by FLIM readout of Förster resonance energy transfer between the PAR chain and the tagged protein. Like this, the intracellular dynamics of protein PARylation shall be monitored with high spatial and temporal resolution in living cells.

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