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A01 Dominic Grün (PhD project)

A02 Eirini Trompouki (PhD project)

A03 Tanja Vogel (PhD project)

A04 Thomas Manke (PhD project)

A05 Wolfgang Driever (PhD project)

A06 Thomas Laux (PhD project)

B01 Ulrich Maurer (PhD project)

B02 Melanie Boerries (PhD project)

B03 Andreas Hecht (PhD project)

C01 Wolfgang R. Hess (PhD project)

C02 Annegret Wilde (PhD project)

D01 Rolf Backofen (PhD project)

D02 Rolf Backofen (Postdoc project)

A01 Dominic Grün
Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
Quantitative single cell biology

 This project will follow the temporal succession of haematopoietic differentiation transitions in Reaggregate Thymus Organ Culture (RTOC) with single cell resolution.

We will

  • characterize the population composition of precursor cells in the thymus at subsequent time points, and investigate the differentiation dynamics of all haematopoietic cell lineages populating the thymus.
  • perform a detailed analysis of the kinetics of progenitor stage transitions, in order to understand the dynamics of cell transitions through subsequent niches and the underlying gene regulatory changes.
  • test the response of the differentiation trajectories to a perturbation of the Notch signalling pathway, which is critical for T cell differentiation.
position PhD position (65% TVL E13)
Research question Investigating the dynamics of thymocyte differentiation and the underlying gene regulation in single cell resolution
Model system mouse
Methods organ culture, FACS, single cell RNA seq and computational methods to identify and model cell states and differentiation trajectories
Lab homepage http://ie-freiburg.mpg.de/4558503/Gruen

 


A02 Eirini Trompouki
Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
Haempatopoiesis

 This project will provide insights into the transcriptional dynamics of haematopoietic stem cells under perturbed inflammatory signalling and the mechanism of activation of Retinoic acid inducible gene 1 Like Receptors (RLRs) in the absence of viral infection. It dissects how RLRs modulate haematopoiesis over time (HSC formation, expansion and maintenance) in different compartments (AGM, FL and BM) We will

  • explore single cell transcriptomes of Rig-I-/- and Mda5-/- HSCs in AGM, FL and BM.
  • identify transcription factors responsible for transcriptional changes in knockout mice.
  • discover new RLR ligands under steady state and regenerative conditions.
position PhD position (65% TVL E13)
Research question Control of haematopoiesis by RNA helicases
Model system  mouse
Methods FACS, single cell RNA-seq, ATAC-seq, Motif analysis, CLIP-seq
Lab homepage http://ie-freiburg.mpg.de/de/trompouki

 


A03 Tanja Vogel
Institute of Anatomy and Cell Biology, University Freiburg, Germany
Neurodevelopment, epigenetics

 This project resolves the mechanism of histone methyltransferase DOT1L-associated defects in CNS development and aims at understanding DOT1L-mediated transcriptional control and chromatin properties. Analysing mother and daughter cells that arise at different developmental time points and populate different locations depending on the division mode shall reveal the spatio-temporal dynamics of DOT1L function with high resolution. We will

  • explore the DOT1L-dependent transcriptome in individual cells in one cell lineage during cortical differentiation.
  • explore the DOT1L-dependent transcriptome and chromatin properties in progenitors and differentiated progeny after DOT1L-deletion in larger, yet defined cell populations of progenitors or differentiated neurons.
position PhD position (65% TVL E13)
Research question Spatio-temporal adaptation of DOT1L-mediated transciptional control within defined cell lineages during cortical development
Model system mouse
Methods microinjection, single cell RNA-seq, ChIP-seq, in utero electroporation, FACS
Lab homepage  http://www.anatomie2.uni-freiburg.de/en/science/vogel

 


A04 Thomas Manke
Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany
Deep sequencing data analysis

 This project aims at understanding the chromatin state and genome organisation during neuronal differentiation at high resolution. The resolution at cellular level will be complemented by an accurate molecular readout from deep sequencing, and by a high spatial resolution at the level of genome conformation. We will

  • map histone dynamics and chromatin states in developing neuronal cells.
  • map spatial organisation and chromatin conformation in developing neuronal cells.
position PhD position (65% TVL E13)
Research question Understanding the dynamic organisation of chromosomes in 3D during neural differentiation
Model system mouse
Methods small cell number ChIP-seq, refinement of algorithms and workflows, Hi-C, FACS, in utero electroporation
Lab homepage http://bioinfo.ie-freiburg.mpg.de

 


A05 Wolfgang Driever
Institute of Biology, University Freiburg, Germany
Embryonic development

 This project characterises dynamic transcriptome changes between neural stem cells, proliferating precursors, differentiating and mature DA neurons in vivo, and aims to identify specific epigenetic mechanisms involved in these transitions. To resolve potential specific Mll1 activities, we will investigate effects of its inhibition or knock-out on the dynamic transcriptome during neurogenesis. We will

  • Characterise dynamic transcriptome profiles during neurogenesis from stem cell to mature DA neuron. These data will define steps in neurogenesis and identify potential new regulators of dopaminergic neurogenesis.
  • Identify epigenetic mechanisms of DA neurogenesis by identifying specific genes regulated by TrxG/Mll1 dependent mechanisms.
position  PhD position (65% TVL E13)
Research question Transcriptional and epigenetic mechanisms controlling transition states from neural stem cells to dopaminergic neurons in vivo
Model system zebrafish
Methods  FACS, laser microdissection, single cell RNA-seq, ChIP-seq, fluorescent in situ hybridisation
Lab homepage http://bio1.uni-freiburg.de/ebio-en/driever-lab

 


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

 In this project we want to resolve the role of chromatin dynamics for the specification of cell fate in the CSC niche. The spatial dynamics will be investigated along the WOX5-protein gradient in the CSC niche and data along the temporal axis will be obtained from CSC niches at different ages. We will

  • Isolate nuclei from specific cell types of the CSC niche by fluorescence activated nuclei sorting (FANS).
  • Generate cell specific RNA-seq and ChIP-seq profiles.
  • identify candidate genes differentially regulated in the CSC niche by WOX5-mediated chromatin changes and aging.
  • verify candidate genes in vivo.
position PhD position (65% TVL E13)
Research question Spatio-temporal transcriptional control of the Arabidopsis root stem cell niche by chromatin modifications
Model system Arabidopsis thaliana
Methods  FANS, small cell number ChIP-seq, RNA-seq, in situ hybridisation
Lab homepage  http://biologie.uni-freiburg.de/LauxLab/

 


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

 This project investigates the effects of PI3K/AKT/GSK-3 and CDK-9 dependent phosphorylation of TIP60 on transcriptional control and chromatin properties. We will:

  • investigate the spatial distribution of wildtype TIP60 as compared to the phosphorylation mutants TIP60S86A and TIP60S90A on a genome wide level.
  • Analyse histone 4 acetylation, S2P and S5P RNA PolII distribution patterns in cells expressing wild-type TIP60, TIP60S86A, and TIP60S90A, and correlate RNA expression in these cells.
  • Analyse the spatial distribution of TIP60 and gene expression after pharmacological inhibition of PI3K, GSK-3, and CDK-9 kinase activity and correlate these data to the genome-wide distribution data obtained from TIP60 wildtype and phosphorylation mutants.
position PhD position (65% TVL E13)
Research question  Genome-wide analysis of the role of TIP60 phosphorylation in transcriptional regulation
Model system human cancer cell line
Methods CRISPR-rAAV knock-in, ChIP-seq, RNA-seq
Lab homepage  http://www.mol-med.uni-freiburg.de/mom-en/mau

 


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

 This project elucidatse epigenetic and transcriptional changes in the stroma of melanoma microenvironment that foster melanoma cell growth, survival and invasion. We will:

  • identify histone modifications and transcriptional regulation in the spatio-temporal communication between melanoma cells (from different origin and mutation status) and fibroblasts.
  • study mechanisms of treatment resistance of melanoma cells in the presence of cancer-associated fibroblasts (CAFs).
  • develop an integrative in silico cell model of melanoma cells and CAFs based on epigenome, transcriptome and phenome.
position PhD position (65% TVL E13)
Research question  Epigenetic control of the tumour microenvironment in melanoma and its impact on treatment resistance
Model system human melanoma cell lines
Methods  ChIP-seq, RNA-seq, RNA-seq, organotypic culture, microdissection, dynamic network modeling
Lab homepage https://www.mol-med.uni-freiburg.de/mom/buschboerries

 


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

 This project aims at understanding the function of SNAIL1 as a transcriptional activator during epithelial-mesenchymal transitions  (EMT). It will study TGFβ-induced gene expression changes, spatio-temporal dynamics of SNAIL1 chromosomal distribution and SNAIL1-dependent changes in chromatin structural features. We will:

  • identify the genes subject to direct transcriptional activation by SNAIL1 during EMT.
  • structurally and functionally characterise cis-regulatory DNA elements involved in SNAIL1-mediated transcriptional activation.
  • identify signal transduction pathways and transcription factors that cooperate with SNAIL1 in gene activation.
position PhD position (65% TVL E13)
Research question  Transcriptional activation by the EMT inducer SNAIL1: identification of cis-regulatory elements, target genes and cooperating signalling networks
Model system human breast epithelial cell line
Methods ChIP-seq, RNA-seq, ATAC-seq, CRISPR-Cas9
Lab homepage https://www.mol-med.uni-freiburg.de/mom/hecht

 


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

 This project resolves the functions, dynamics and regulatory impact of RNA-RBP complexes.
We will:

  • track the composition and visualise the S.6803 RNA-protein landscape.
  • Perform a functional in-depth analysis of selected RNA-protein pairs.
  • Analyse the activity of selected regulators within the bacterial population and identify their intracellular sites of action.
position PhD position (65% TVL E13)
Research question Regulatory non-coding RNAs in cellular decision making
Model system Cyanobacteria
Methods Grad-seq, iCLIP-seq, fluorescence microscopy, flow cytometry
Lab homepage http://www.cyanolab.de

 


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

 The project aims to elucidate how light direction and thus spatial information is sensed and transduced to the motility apparatus, which then leads to the decision at single cell level to move directly and accurately into a given direction. We will:

  • understand the role of Hfq, which is bound to type IV pili, in regulation of RNA processing and identify ribonuclease targets.
  • analyse localisation of motility related RNAs and identify potential transcription-translations centres.
  • identify other factors of the light-dependent localised signal transduction chain.
Position PhD position (65% TVL E13)
Research question Spatio-temporal dynamics in responding to light signals in cyanobacteria
Model system Cyanobacteria
Methods confocal microscopy, iCLIP-seq, RNA-FISH, life cell imaging, RNA-seq
Lab homepage  http://www.bakteriengenetik.uni-freiburg.de

 


D01 Rolf Backofen
Institute of Informatics, University Freiburg, Germany
RNA bioinformatics

 This projectwill  improve and simplify the analysis of the interactome of RBPs. We intend to build up workflows in Galaxy related to major tasks in the analysis of CLIP-seq data. We will:

  • implement a workflow for the basic analysis of CLIP-seq data including pre-processing, peak calling and motif detection.
  • develop a new peak caller that uses negative controls for CLIP-seq data.
  • determine strategies for estimating binding affinities from CLIP-seq data.
position PhD position (100% TVL E13)
Research question Analysis of RNA-protein interactions
Model system high-throughput data from different model organisms
Methods CLIP-seq data analysis, Grad-seq data analysis, generation of workflows, peak calling algorithms, variety of analysis tools in Galaxy
Lab homepage http://bioinf.uni-freiburg.de/

 

 

D02 Rolf Backofen
Institute of Informatics, University Freiburg, Germany
RNA bioinformatics

 The overall goal in this project is to train MeInBio life scientists to perform their own bioinformatics analyses within our Galaxy server, especially in single cell RNA-seq.  We will:

  • Develop visualisation approaches for detecting differentiation pathways that are informed by a user-defined clustering.
  • Integrate tools and workflows for the analysis of singe cell RNA-seq in Galaxy.
  • Train experimentalists on the main Galaxy workflow.
Position  Postdoc position (100% TVL E13)
Research question  Integrated approaches to analyse gene expression
Model system high-throughput data from different model organisms
Methods single cell RNA-seq data analysis and visualisation, integration of different tools, workflow setup, Galaxy
Lab homepage  http://bioinf.uni-freiburg.de/