Research Program B: Functional and Structural Genomics

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Below you will find DKFZ divisions and research groups of the Research Program Functional and Structural Genomics who are interested in recruiting Postdocs within the 2018 DKFZ Postdoctoral Fellowships Selection.

Please note that this is not an exhaustive list and new groups are continously added.

You may also contact the principal investigator of the DKFZ research group of your choice directly to discuss about current possibilities. More information about hiring labs can be found below and descriptions of DKFZ research programs via the general topic locator.

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Signaling and Functional Genomics – Prof. Dr. Michael Boutros

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RESEARCH PROFILE

Our group works on oncogenic signaling pathways and their role in homoeostasis and disease. Genome sequencing have identified many genetic variants, yet their function and interactions often remains unknown. To address this, we perform systematic screens using genetic and chemico-genetic technologies to functionally characterize novel components, understand how they are interconnected and how best to interfere with their aberrant regulation in cancer.

A current particular interest lies on organoid models of gastrointestinal cancer and their multi-omics analysis to understand principle mechanism of tumorigenesis and potentially tailor individualized therapies. Patient derived organoids (PDOs) are physiological 3D tumor models that can be efficiently derived from individual patients' tumors and normal tissues. In the colon, this is based on isolation of Lgr5+ stem cells that form organotypic structures and are expandable in vitro. Organoid isolation from human primary tumors and metastases has enabled the establishment of living patient derived organoid biobanks.

 

POSTDOC PROJECT

The postdoc project will make use of PDOs for the analysis of molecular and phenotypic differences and to understand tumorigenesis, tumor heterogeneity and drug response. Functional image-based screening approaches, single-cell sequencing and CRISPR screens will be used to dissect dysregulated pathways and identify new potential drug targets. The postdoc candidate will join an interdisciplinary team with a background in molecular and cellular biology, bioinformatics and clinical medicine. Both experimental and computational scientists are encouraged to apply.

 

Please visit our website for further information on our research and recent publications.

LINK: https://www.dkfz.de/en/signaling

Somatic Evolution and Early Detection – Dr. Angela Goncalves

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RESEARCH PROFILE and PROJECT TOPICS

Dr. Angela Goncalves  is looking for computational Postdoctoral Scientists to join her group. This is a great opportunity for a self-motivated, innovative and meticulous candidate with excellent communication skills to work in a dynamic laboratory undertaking cutting edge research.

The aim of the group is to understand how mutant clones arise and expand during the stages preceding the development of malignancy. We combine experimental approaches  such as deep DNA sequencing and single-cell RNA sequencing with bioinformatic analyses and statistical modelling to study these early stages, with a long-term view of improving early detection of cancer.  This role is an exciting opportunity to join a multidisciplinary team to study these problems.

We are looking for candidates for projects applying single sequencing to the problems of identifying the cell type of origin in cancer and the effects of somatic mutation on gene expression. Our group has a particular focus on gynaecological cancers of the lower reproductive tract, but we also consider other cancer entities. The post-holder will have access to unique, functional genomics data sets generated in the group and at DKFZ.

Candidates with a background in biology with an interest in quantitative analysis are encouraged to apply. We also welcome candidates with a background in physics, statistics or computer science with interest in computational biology. Programming skills and ability to work as part of a team are essential.

 

Please visit our website for further information on our research and recent publications.

LINK: https://www.dkfz.de/en/somatische-evolution-frueherkennung

RNA Biology and Cancer – Prof. Dr. Sven Diederichs

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RESEARCH PROFILE

The research in the Division of RNA Biology & Cancer focuses on the role of RNA - protein complexes especially in lung and liver cancer including lncRNAs, RNPs and mutations in the non-coding genome space. Our method spectrum spans molecular and cellular biology, biochemistry and bioinformatics including high throughput approaches in human cell model systems.

 

PROJECT TOPICS

A future postdoc project could investigate the function of RNA-dependent protein complexes in cell cycle progression and in epigenetic mechanisms. We have already identified RNA-dependent protein complexes in a proteome-wide approach by mass spectrometry (unpublished), which this project will build on. The project will aim to elucidate the molecular mechanisms of the RNA-dependent protein complex, identify the responsible RNA(s) and establish their functions at the cellular and molecular level in human cancer cells.
References: Goyal A et al. NAR 2017, Diederichs S et al. EMBO Mol Med 2016, Roth A et al. Nature 2015, Nachmani D et al. Nat Commun 2014, Gutschner T et al. Cancer Res 2013, Diederichs S et al. Cell 2007

 

Please visit our website for further information on our research and recent publications.

LINK: http://www.dkfz.de/en/molekulare-rna-biologie

Translational Control and Metabolism – Dr. Fabricio Loayza Puch

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RESEARCH PROFILE

The demand for building blocks in cancer cells differs greatly from the one of a normal cell. In order to divide, a cell must duplicate its protein content, a process that requires large amounts of energy and amino acid resources. To cope with higher demand of energy and building blocks, cancer cells rewire profoundly their metabolic networks. However, the metabolic changes a tumor undergoes to adapt to deregulated growth might expose vulnerabilities that can be exploited for therapy. To exploit amino acid vulnerabilities for cancer therapy, one must first identify which amino acid is the most restrictive to the tumor. Our laboratory uses a combination of innovative genomics tools, molecular biology, animal models, and bioinformatics to uncover these metabolic limitations in cancer. Recently, we developed a novel approach to detect restrictive amino acids in cells and tumors. The rationale of our approach is based on differential ribosome codon reading (diricore); we make use of ribosome profiling to detect ribosomes stalled at specific codons. The accumulation of ribosomes at a particular codon indicates that the corresponding aminoacylated tRNA might be limiting and suggests a deficiency of the amino acid. The diricore approach can be used as a platform to sense these amino acid deficiencies in cells and tumors and to expose the weaknesses of tumor's metabolic remodeling.

 

PROJECT TOPICS

We're looking for highly motivated individuals who would like to apply innovative genomics approaches to explore the regulation of mRNA translation in cancer. We are particularly interested in uncovering metabolic limitations in cancer and in exploring the role of protein synthesis in invasion and metastasis.

 

LINK: website not available yet

Dr. Duncan Odom

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RESEARCH PROFILE

Dr Odom’s laboratory studies how genetic sequence information shapes the cell's DNA regulatory landscape and thus the trajectory of cancer genome evolution. To date, their use of interspecies comparisons of matched functional genomic data has resulted in fundamental discoveries, including the extensive and rapid turn-over of tissue-specific transcription factor binding (Schmidt et al Science 2010, Stefflova et al Cell 2013), insulator elements (Schmidt et al Cell 2012), polymerase occupancies (Kutter et al Nature Genetics 2011), and enhancer activities (Villar et al Cell 2015) during organismal evolution, as well as the mechanisms underlying this regulatory plasticity (Wilson et al Science 2008). To demonstrate that genetic sequences were the major determinant of transcription and transcriptional regulation, the Odom lab re-purposed a fascinating aneuploidy mouse model of Down syndrome (previously developed by collaborators) that carries an almost complete copy of human chromosome 21 (Ward et al Molecular Cell 2013). Profiling the functional behaviour of a human chromosome in a mouse nucleus provided an elegant and powerful demonstration that cis-acting sequences have a greater impact than trans influences on transcription factor binding, chromatin state, and gene expression. Recently, his laboratory has begun exploiting single-cell RNA-sequencing and large-scale whole genome sequencing in understanding molecular evolution. Specifically, the Odom lab have recently used single-cell transcriptional analysis to conclusively demonstrate that ageing results in substantial increases in cell-to-cell transcriptional variability (Martinez et al Science 2017), as well as undertaken a large-scale analysis of how genetic and epigenetic differences between alleles can fundamentally alter the location and intensity of mutagenesis during tumour evolution.

 

PROJECT TOPICS

The Odom lab will be re-opening at DKFZ in early 2019. Postdoctoral opportunities will be available to work particularly in the areas of single-cell functional genomics, and the influence of genetic sequence variation on cancer genome evolution. Successful candidates should be highly versant with a diversity of modern genomics methods, and able to perform basic computational biology to facilitate interaction with dedicated computational collaborators. 

 

LINK: not available yet

Chromatin Networks – Prof. Dr. Karsten Rippe

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RESEARCH PROFILE

We investigate how epigenetic signals like histone and DNA methylation are linked to chromatin remodeling and determine cell-type specific gene expression programs via distinct patterns of active or repressive chromatin states. These patterns are 'memorized' through cell division by interconnected networks of factors that set, remove or readout chromatin marks. Any errors that occur in this process can lead to aberrant gene regulation, DNA replication or DNA repair associated with cancer and other diseases. To understand how the underlying chromatin networks operate we integrate deep-sequencing and fluorescence microscopy methods with quantitative biophysical modeling.
In our current work we dissect the interplay of genetic and epigenetic heterogeneity in different leukemias to rationalize why cell subpopulations respond differently (or not at all) to drugs. By applying genome-wide sequencing methods (RNA and accessible chromatin) to single cells we identify differences between individual cells as well as changes of the cell type composition of the whole population upon drug treatment.

 

PROJECT TOPICS

For this work we are seeking a postdoctoral fellow to conduct the bioinformatic analyses of single cell sequencing data (including machine learning approaches) and to subsequently develop models that predict features of the cancer pathophenotype. We are looking for someone with good computational skills and experience in model development who wants to work in an interdisciplinary team. The fellow will have the possibility to further shape the theoretical single cell sequencing work of the division as we will continuously expand these activities.

 

LINK: https://www.dkfz.de/en/chromatin-networks/index.php , external Bioquant website

Computational Genomics and Systems Genetics – Dr. Oliver Stegle

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RESEARCH PROFILE

Our interest lies in computational approaches to unravel the genotype– phenotype map on a genome-wide scale. How do genetic background and environment jointly shape phenotypic traits or causes diseases? How are genetic and external factors integrated at different molecular layers, and how variable are these molecular readouts between individual cells and in spatio-temporal contexts?

We use statistics as our main tool to answer these questions. To make accurate inferences from high-dimensional 'omics datasets, it is essential to account for biological and technical noise and to propagate evidence strength between different steps in the analysis. To address these needs, we develop statistical analysis methods in the areas of gene regulation, genome wide association studies (GWAS) and single-cell biology.

Our methodological work ties in with experimental collaborations and we are actively developing methods to fully exploit large-scale datasets that are obtained using the most recent technologies.

 

PROJECT TOPICS

As a new division at DKFZ, we are initiating a research program at the interface of human genetics, oncology and single-cell biology. We are particularly interested in candidates with a strong statistical and computational training. Projects include method development for single-cell omics, spatial technologies and multi-omics. However, we are also open to interdisciplinary projects that bridge our expertise with experimental groups (e.g. Michael Boutros, Duncan Odom, Andreas Trumpp).

 

LINK: website not available yet

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