Research Projects
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.
Click on the project to jump to the more detailed description.
If not indicated otherwise all projects will accept a new PhD student in September 2023.
Alumni group:
A01 Prof. Dr.Tanja Vogel:
Spatio-temporal analysis of forebrain development on a single cell level
Institute of Anatomy and Cell Biology, University Freiburg, Germany
The Vogel lab researches the influence of epigenetic modifications of histones during central nervous system development. We are particularly interested in the function of the histone methyltransferase DOT1L on the specification of stem and progenitor cells during development of the cerebral cortex. We recently showed that DOT1L has a high plasticity leading to pleiotropic effects during specification of the cerebral neocortex layers (Franz et al, 2019), to alterations of the enhancer landscapes (Ferrari et al, 2020), and based on single cell analyses, to an adaptation of the metabolic program during neuronal differentiation (Appiah et al, 2022). In our MeInBio project we now further resolve the mechanism of DOT1L-associated defects in cerebral cortex development in mice and humans. Specifically, we aim at understanding DOT1L-mediated transcriptional control and how it impacts chromatin properties and enhancer landscapes to prevent neuronal differentiation and to preserve stem cell states. We therefore explore the DOT1L-dependent transcriptome and epigenome in individual progenitor populations during cortical differentiation. The future project shall advance our understanding on human cortical development by exploring the DOT1L-dependent transcriptome and epigenome in single cells during human brain organoid differentiation, with spatio-temporal resolution. We aim to resolve the different stem cell populations, their differentiation potential and trajectories and to resolve chromatin-mediated mechanisms of epigenetic control of gene expression networks.
Main methods: single cell RNA-seq, single cell ATAC-seq, single cell Cut&Run, spatial transcriptomics, bioinformatics analyses, human brain organoid differentiation, iPSC, ChIP-seq, FACS
Lab homepage: https://www.developmentalneuroepigenetics.uni-freiburg.de/
A02 Dr. Eirini Trompouki:
Transcriptional dynamics of hematopoietic stem cells
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
We are interested in the transcriptional dynamics of haematopoietic stem cells (HSCs) under perturbed inflammatory signaling or during therapeutic treatment. In MeInBio, we dissect in mice how Retinoic acid inducible gene 1 Like Receptors (RLRs) modulate haematopoiesis over time. We aim to understand the molecular mechanisms that underlie chemotherapeutic responses in murine HSCs and 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
lab homepage http://ie-freiburg.mpg.de/de/trompouki
A03 Dr. Nina Cabezas-Wallscheid:
Regulation of hematopoietic stem cell dormancy
A04 Dr. Thomas Manke:
Genome organization during differentiation, Deep sequencing data analysis
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
The Manke group develops tools for the analysis and visualisation of deep-sequencing data. In a long-running collaboration with the lab of Prof. Vogel, we aim at understanding the chromatin state and genome organisation during murine neuronal differentiation at single-cell resolution. Using advanced machine learning methods, we are integrating multi-modal data from gene expression and chromatin accessibility to infer cell-type specific regulatory networks.
The PhD project will utilise spatial transcriptomics and place these networks into the context of a spatially evolving brain. For candidate transcription factors, we will also use highly sensitive assays to map their targets genome-wide. The ultimate goal is 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
Lab homepage: http://bioinfo.ie-freiburg.mpg.de
A05 Prof. Dr. Wolfgang Driever:
Epigenetic mechanisms controlling transition states in neural differentiation
Institute of Biology, University Freiburg, Germany
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 identify specific epigenetic mechanisms involved in these transitions. Currently, we aim at characterizing dopaminergic neurogenesis from neural stem cells in the subpallial proliferation zone in zebrafish.
Main methods: FACS, single cell RNA-seq,fluorescent in situ hybridization
Lab homepage: http://bio1.uni-freiburg.de/ebio-en/driever-lab
A06 Prof. Dr. Thomas Laux:
Plant development
Institute of Biology, University Freiburg, Germany
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. We currently 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
Lab homepage: http://biologie.uni-freiburg.de/LauxLab/
A07 Dr. Sebastian Preissl:
Gene regulation in health and disease
Institute of Experimental and Clinical Pharmocology and Toxicology, University Freiburg, Germany
The Preissl lab has a focus on the regulation of transcription, including epigenetic mechanisms. The main objectives of the lab’s research are to build a molecular framework of how external cues are integrated to regulate gene expression and how cells communicate with each other in the tissue context. We combine single-cell transcriptomics, epigenomics and spatial genomics with in vivo and in vitro model systems to understand the molecular and gene regulatory basis of development, aging, and different pathologies including heart disease and kidney disease.
Main methods: multiplexed error-robust RNA FISH (MERFISH), single nucleus multiomics, in vitro differentiation models, CRISPR gene editing
Lab homepage: https://www.preissllab.org/
A08 Dr. Sagar:
Unraveling the mechanisms of unconventional T cell lineage specification using single-cell multimodal profiling and lineage tracing
Department of Medicine, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Medical Center – University of Freiburg, Germany
We employ single cell sequencing methods (single cell RNA-Seq, CITE-Seq, single-cell TCR repertoire sequencing, single-cell ATAC-Seq) and uses state-of-the-art single-cell computational methodologies across different modalities, tissues and species for comparative analyses to acquire an improved understanding of the underlying mechanisms of γδ T cell functions.
The project has two major goals: (1) to develop protocols that enable the combination of genetic lineage tracing with single-cell multimodal profiling using the 10x Genomics platform, and (2) to perform a thorough multimodal analysis of T cell clonal fate maps, in order to uncover the homologous and distinct regulatory principles that govern lineage choices of unconventional T cells.
Main methods: single cell RNA-seq and bioinformatics analyses
Lab homepage: https://www.uniklinik-freiburg.de/medizin2/forschung/ag-sagar.html
B02 PD Dr. Ulrich Maurer:
Cell death and survival
Institute of Molecular Medicine and Cell Research, University Freiburg, Germany
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 and 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
Lab homepage: http://www.mol-med.uni-freiburg.de/mom-en/mau
B03 Prof. Dr. Dr. Melanie Börries:
Systems biology
Institute of Molecular Medicine and Cell Research, University Freiburg, Germany
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. We identify 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.
By using CRISPR/Cas9 gene editing to target PTEN, we are currently investigating the contribution of the PI3K/AKT pathway to resistance mechanisms. The next PhD candidate will investigate the role of this pathway activation in remodeling of the tumor microenvironment (TME). The project aims to explore transcriptional changes during melanoma invasion and to develop an integrative in silico predictive model of cell communication.
Main methods: CRISPR/Cas, RNA-seq, cell culture, in silico analysis and data integration
Lab homepage: https://www.uniklinik-freiburg.de/institut-fuer-medizinische-bioinformatik-und-systemmedizin/englisch/en.html
B04 Prof. Dr. Andreas Hecht:
Tumourigenesis
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. We also 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
Lab homepage: https://www.mol-med.uni-freiburg.de/mom/hecht
B05 Prof. Dr. Oliver Schilling:
Proteomics, Proteolytic signaling
Institute of Clinical Pathology, University Freiburg, Germany
The Schilling laboratory employs proteomics and proteogenomics to better understand disease processes, e.g., for solid tumors. The planned project will probe the spatial proteome biology of solid tumors using state-of-the-art methods in mass spectrometry imaging (MSI). We will advance the bioinformatic processing of MSI data to enhance the proteome coverage in situ. Moreover, we will integrate MSI-based, highly multiplexed immune-detection of proteins. The project aims to understand intratumor heterogeneity of proteome biology and characterize cell-cell and cell-matrix interactions with novel tools.
Main methods: several proteomics techniques, computational and statistical methods
lab homepage https://www.uniklinik-freiburg.de/pathologie/forschung/ag-schilling.html
B06 Prof. Dr. Dr. Bertram Bengsch:
Translational Systems Immunology
Department of Medicine, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Medical Center – University of Freiburg, Germany
The lab uses systems immunology approaches to understand cellular mechanisms of immune dysregulation in human disease and during immunotherapy of cancer. We combine mass cytometry data with single cell profiling techniques and spatial transcriptomics. We aim to integrate the different methods to identify immune cell – cancer cell interactions in anatomic niches associated with disease outcomes.
The PhD project uses imaging mass cytometry and spatial transcriptomics and MALDI imaging to profile the tumor immune microenvironments and microanatomic niches in hepatobiliary cancer. Single-cell RNASeq data will be used to inform deconvolution of spatial transcriptome data together with the co-registered high-resolution imaging data. The project aims to integrate the different spatial omics methods, to identify immune cell – cancer cell interactions in anatomic niches associated with disease outcomes and to further establish a pipeline for rapid semi-supervised generation of spatial reports of actionable targets suitable for personalized therapy decisions.
Main methods: mass cytometry, MALDI imaging, single cell RNA-seq, bioinformatics analyses
Lab homepage: https://www.uniklinik-freiburg.de/medizin2.html
C01 Prof. Dr. Wolfgang R. Hess:
Genetics and Experimental Bioinformatics in the Exploration of Genetic Dark Matter in Bacterial Cells
Institute of Biology, University Freiburg, Germany
Our lab is located at the interface of bioinformatics, synthetic biology, experimental RNA biology and microbial systems biology. We have a long-standing interest in cyanobacteria and other photosynthetic organisms and their impact on the environment and in their biotechnology. Current research activities are centred around the analysis of transcriptomic and epigenomic datasets to characterize the „genetic dark matter”. This includes the identification of novel regulatory RNA molecules and previously unknown small proteins to understand their functions. In MeInBio we resolve the functions, dynamics and regulatory impact of RNA–protein interactions.We track the composition and visualise the RNA-protein landscape in the unicellular model cyanobacteriumSynechocystis and perform functional in-depth analyses of selected RNA-protein pairs. The current projectaims at deciphering the interaction between non-coding RNAs and functionally important cognate RNA-binding proteins in post-transcriptional regulation and intracellular targeting.
Main methods: construction of engineered strains, RNA-seq and iCLIP-seq, single-cell sequencing of bacterial cells, gradient profiling by sequencing, bioinformatic prediction of RNA:RNA and RNA:protein interactions
Lab homepage: http://www.cyanolab.de
C02 Prof. Dr. Annegret Wilde:
Bacterial Genetics
Institute of Biology, University Freiburg, Germany
The Wilde group investigates the spatio-temporal dynamics of signalling processes in cyanobacteria. The MeInBio project studies RNA metabolism and analyses the spatiotemporal localization patterns of mRNAs in a cyanobacterial cell, and the dependence of these patterns on active transcription and translation. In the upcoming project, we want to artificially change the localization patterns of RNAs in order to assess the impact of subcellular localization on their function. These analyses will highlight the importance of posttranscriptional regulation for rational design of prokaryotic biofactories in synthetic biology.
Main methods: RNA-FISH, FLIM microscopy, RNA-seq, iCLIP
Lab homepage: http://www.bakteriengenetik.uni-freiburg.de
D01 Prof. Dr. Rolf Backofen:
RNA bioinformatics, analyses of RNA-protein interactions
Institute of Informatics, University Freiburg, Germany
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
Lab homepage: http://bioinf.uni-freiburg.de/
D02 Prof. Dr. Harald Binder:
Machine Learning and Modeling
Institute of Medical Biometry and Statistics, University Freiburg, Germany
We develop machine learning techniques, specifically approaches based on deep neural networks, for modeling single-cell sequencing data. The focus currently is on modeling temporal patterns. Subsequently we will be incorporating further data types in a multi-omics approaches.
Main methods: deep Boltzmann machines, variational autoencoders (VAEs), joint modeling
Lab homepage: http://www.imbi.uni-freiburg.de/persons-de/binderh-de/person_view_de/
associated Prof. Dr. Anna Köttgen:
Genetic Epidemiology
Institute of Genetic Epidemiology, University Freiburg, Germany
The Kottgen lab uses data from epidemiological and clinical studies to gain insights into human physiology and the pathophysiology of complex traits and diseases. We are especially interested in kidney and metabolic diseases. Through the integration of genome-wide genetic and metabolomic data, we recently showed that the levels of metabolites in urine are under strong genetic influence and capture processes related to metabolite absorption, distribution, metabolism and excretion. In the future, we want to use multi-Omic data from thousands of study participants to better understand if genetic differences on metabolite levels in plasma versus urine reflect specific metabolic functions of the kidney, and to what extent these are influence by patient characteristics.
Main methods: genome-wide association studies, analysis of non-targeted MS-based metabolomics, single cell RNA- and ATAC-seq, bioinformatics analyses
Lab homepage: https://www.uniklinik-freiburg.de/genetic-epidemiology.html
Alumni group:
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
now Würzburg Institute of Systems Immunology, University of Würzburg
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
lab homepage (MPI) http://ie-freiburg.mpg.de/4558503/Gruen
lab homepage (Uni Würzburg) https://www.med.uni-wuerzburg.de/en/systemimmunologie/research/quantitative-single-cell-biology-of-the-immune-system-gruen-lab/