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MeInBio research spans many different model systems: from bacteria to human cancer cells. MeInBio researchers use these systems to understand how cells react to stimuli from the environment, and how cells control their development on a transcriptional level. In vivo, many similar looking cells in close vicinity may act differently, therefore MeInBio researchers try to analyze very small populations of cells, or single cells.

                     Dominic GrünEirini TrompoukiTanja VogelThomas MankeWolfgang DrieverThomas LauxUlrich MaurerMelanie BörriesAndreas Hecht                            Wolfgang HessAnnegret WildeRolf BackofenHarald Binder




Dominic Grün   A01 Dominic Grün 

Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
Quantitative single cell biology in hematopoietic differentiation

The Grün lab investigates how gene expression programs are regulated with spatial and temporal precision during stem cell differentiation in the presence of gene expression noise. In MeInBio we currently study mouse hematopoiesis as a model to understand differentiation transitions in single cells. We perform a detailed analysis of progenitor stage transitions at subsequent timepoints of embryonic development, where hematopoiesis occurs within different tissue contexts. By co-analyzing the hematopoietic cell populations with the endothelial niche at single-cell resolution, we are investigating the role of the microenvironment in determining hematopoietic cell fate. In the future project we will focus on the liver, which is an ideal model for cellular plasticity, in order to study perturbations in liver disease and cell state changes during liver regeneration in both, human organoids and mouse models at spatial single-cell resolution. 

Main methods: seqFISH, single cell RNA-seq, computational and statistical methods, FACS

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Eirini Trompouki   A02 Eirini Trompouki

Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

Transcriptional dynamics of hematopoietic stem cells

We are interested in the transcriptional dynamics of haematopoietic stem cells (HSCs) under perturbed inflammatory signaling or during therapeutic treatment. In the current MeInBio project, we dissect in mice how Retinoic acid inducible gene 1 Like Receptors (RLRs) modulate haematopoiesis over time. In the future project, we aim to understand the molecular mechanisms that underlie chemotherapeutic responses in murine HSCs. We would like to identify how chemotherapy leads to robust gain of chromatin accessibility and understand mechanistically how waves of changes in gene expression are achieved. 


Main methods: ATAC-seq, HSC cultures, cell cycle analysis, GRO-seq, ChIP-seq

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Tanja Vogel    A03 Tanja Vogel
Institute of Anatomy and Cell Biology, University Freiburg, Germany
Spatio-temporal analysis of forebrain development on a single cell level

The Vogel lab researches the influence of epigenetic modifications of histones during central nervous system development. We are especially interested in the function of the histone methyltransferase DOT1L on the specification of stem and progenitor cells during development. We recently showed that DOT1L has a high plasticity leading to pleiotropic effects during specification of the cerebral neocortex layers (Franz et al, 2018).  The MeInBio project further resolves the mechanism of DOT1L-associated defects in cerebral cortex development in mice, and aims at understanding DOT1L-mediated transcriptional control and chromatin properties. We explore the DOT1L-dependent transcriptome in individual cells during cortical differentiation. In the future project we want to resolve how DOT1L-mediated transcriptional control and chromatin landscape impact on stem cell properties and neuronal differentiation. We are going to explore the DOT1L-dependent transcriptome and epigenome in single cells during mouse and human cortical differentiation

Main methods: single cell RNA-seq, single cell ATAC-seq, bioinformatics analyses, organoid differentiation, ChIP-seq, FACS

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Thomas Manke   A04 Thomas Manke
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
Genome organization during differentiation, Deep sequencing data analysis

The Manke group is constantly developing new methods and tools for the analysis and visualization of deep-sequencing data. In MeInBio we aim at understanding the chromatin state and genome organisation during murine neuronal differentiation at high resolution. The resolution at cellular level will be complemented by an accurate molecular readout from deep sequencing. The future project aims at dynamic mapping of the transcription factor network during murine cortical differentiation. We plan to develop a joint model for chromatin- and sequence-dependent control of gene expression during neuronal differentiation.

Main methods: ChIP-seq/RELACS, single cell ATAC-seq, bioinformatics algorithm and tool development, cell culture

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Wolfgang Driever   A05 Wolfgang Driever
Institute of Biology, University Freiburg, Germany
Epigenetic mechanisms controlling transition states in neural differentiation

The Driver lab has a long-standing interest in investigating signaling and transcriptional networks that control stem cell development during embryogenesis. In MeInBio we characterise dynamic transcriptome changes between neural stem cells, proliferating precursors, differentiating and mature neurons in zebrafish in vivo, and aim to identify specific epigenetic mechanisms involved in these transitions. In the next project we will characterize dopaminergic neurogenesis from neural stem cells in the subpallial proliferation zone in zebrafish.

Main methods: FACS, single cell RNA-seq,fluorescent in situ hybridization

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Thomas Laux   A06 Thomas Laux
Institute of Biology, University Freiburg, Germany
Plant development

The Laux lab studies the mechanisms of cell fate specification in the model plant Arabidopsis thaliana, using the stem cells of root and shoot meristems. In the MeInBio project we want to resolve the role of chromatin dynamics for the specification of cell fate in the CSC niche. The spatial dynamics are investigated along the WOX5-protein gradient in the CSC niche and along the temporal axis from CSC niches at different ages. In the future project, the PhD student will study the chromatin accessibility of stem cell niche cells and the effect of WOX5 on it.

Main methods: Nuclei sorting (FANS), bulk and single cell RNA-seq, ChIP-seq, ATAC-seq, computational analyses 

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Ulrich Maurer   B01 Ulrich Maurer
Institute of Molecular Medicine and Cell Research, University Freiburg, Germany
Cell death and survival

The Maurer group aims at understanding how growth factor availability and stress signals are sensed by cells and integrated into cell signaling pathways, e.g. by posttranslational modifications like phosphorylation or acetylation. In MeInBio we investigate the role of TIP60 phosphorylation in transcriptional regulation in human cancer cells. We analyse the spatial distribution of wild-type and mutated TIP60 and their influence on transcriptional control and chromatin properties. In the future project we want to explore the role of GSK-3b for NF-kB activity and identify GSK-3b dependent NF-kB target genes. The genome wide analysis of the crosstalk of PI3K and NF-kB signaling will improve our understanding of the regulation of inflammation and cell death. 

Main methods: Cut&Run, CRISPR-rAAV knock-in, RNA-seq

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Melanie Börries   B02 Melanie Börries
Institute of Molecular Medicine and Cell Research, University Freiburg, Germany
Systems biology 

The group of Melanie Börries focuses on the development and verification of mathematical models for cellular behavior and cell communication from an initial stimulus to the final phenotype. The MeInBio project elucidates epigenetic and transcriptional changes in the stroma of human melanoma microenvironment that foster melanoma cell growth, survival and invasion. We identify histone modifications and transcriptional regulation in the spatio-temporal communication between melanoma cells (from different origin and mutation status) and fibroblasts, and relate this to mechanisms of treatment resistance. In the future project we will focus on understanding the role of the PI3K-AKT pathway in the modulation of the tumor-stroma crosstalk in melanoma. We will characterize the intrinsic drug resistance and paracrine signaling profile of a CRISPR/Cas9 mediated PTEN knockout and identify dynamic transcriptional and chromatin changes during the crosstalk between melanoma cells and fibroblasts. We will then develop an integrative in silico model of melanoma cells and fibroblast based on epigenome, transcriptome and phenome. 

Main methods:  CRISPR/Cas, RNA-seq, cell culture, ATAC-seq, in silico analysis and data integration

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Andreas Hecht   B03 Andreas Hecht
Institute of Molecular Medicine and Cell Research, University Freiburg, Germany

The Hecht group investigates the transcriptional regulation of oncogenes and tumour suppressor genes in colorectal tumourigenesis and deciphers transcriptional circuits underlying epithelial-to-mesenchymal transition (EMT) in cancer cells. In MeInBio we currently study TGFβ-induced gene expression changes during EMT, spatio-temporal dynamics of SNAIL1 chromosomal distribution and SNAIL1-dependent changes in chromatin structural features. The future project will use intestinal organoids from genetically engineered mouse models to investigate the genetic prerequisites and the environmental factors which prime cancer cells for TGFβ-inducible collective invasion. 

Main methods: single-cell /bulk RNA-seq, single cell/bulk ATAC-seq, CUT&RUN, genome editing with CRISPR/Cas9

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Wolfgang Hess   C01 Wolfgang R. Hess
Institute of Biology, University Freiburg, Germany
Genetics, Experimental Bioinformatics

The Hess group researches the function of cyanobacteria by the analysis of transcriptomic and epigenomic datasets to characterize regulatory RNAs, epigenetic modifications and small proteins. In MeInBio we resolve the functions, dynamics and regulatory impact of RNA-RBP (RNA binding proteins) complexes. We track the composition and visualise the RNA-protein landscape in the unicellular cyanobacterium Synechocystis sp. PCC 6803 (S.6803) and perform a functional in-depth analysis of selected RNA-protein pairs. The future project aims at deciphering the interaction between non-coding RNAs and functionally important cognate RNA-binding proteins.  

Main methods: construction of complementation strains, iCLIP-seq,  rec-YnH yeast two and three-hybrid-based screening

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Annegret Wilde   C02 Annegret Wilde
Institute of Biology, University Freiburg, Germany
Bacterial Genetics

The Wilde group investigates  the spatio-temporal dynamics and signalling processes in responding to light signals in cyanobacteria. The MeInBio project identifies ribonuclease targets and other factors of the light-dependent localized signal transduction chains in cyanobacteria. In the upcoming project, we want to analyse the spatiotemporal localization patterns of RNase E and mRNAs encoding cytoplasmic membrane proteins, and the dependence of these patterns on active transcription and translation.

Main methods: single-molecule RNA-FISH, FLIM microscopy, RNA-seq, iCLIP

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Rolf Backofen   D01 Rolf Backofen
Institute of Informatics, University Freiburg, Germany
RNA bioinformatics, analyses of RNA-protein interactions

The Backofen group develops and uses bioinformatics tools to investigate the influence and function of regulatory RNAs in diverse cellular systems. In MeInBio we improve and simplify the analysis of the interactome of RNA binding proteins. We implement a workflow for the basic analysis of CLIP-seq data including pre-processing, peak calling and motif detection. We also develop a new peak caller that uses negative controls for CLIP-seq data and determine strategies for estimating binding affinities from CLIP-seq data.

Main methods: bioinformatics of CLIP-seq and Grad-seq data analysis, generation of workflows, peak calling algorithms, variety of analysis tools in Galaxy including tools for the analysis of single cell RNA-seq data

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Harald Binder   D03 Harald Binder
Institute of Medical Biometry and Statistics, University Freiburg, Germany

The Binder group is interested in statistical modeling of molecular measurements. In MeInBio we develop statistical tools for designing single cell sequencing experiments. This leads to recommendations and statistical guidelines for sample size and experimental design when investigating dynamic processes with a small number of cells. The upcoming project will investigate single cell ATAC-seq data with small cell numbers by adapting deep generative approaches.


Main methods: deep Boltzmann machines, variational autoencoders (VAEs), joint modeling 

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