Scientific Tools

 
Mouse genetics and virus-based site-specific manipulations

To study gene function and disease mechanisms in vivo, we are generating and using transgenic mouse models as
well as site-specific manipulations of neuronal targets via viral injections. Mouse models include:

• Classical loss- and gain-of-function mouse lines: Knock-out and transgenic mice, injection of shRNAs and overexpression vectors
• Tools to control target expression in a cell-type and time-specific manner: Cell-specific, drug- or activity-inducible Cre and Flp recombinases
• Cell-specific enrichment technologies: RiboTag mice, tAGO2 mice, INTACT mice, RNA-guided nucleases – e.g. CRISPR/Cas system
• Chemogenetic and optogenetic approaches for altering neuronal activation or inhibition in cell- and site-specific manners

Genetically Engineered Mouse Models core unit (MPIP)

Veterinary Resources department (WIS)

Virus Production core unit (MPIP)

   
Visualizing the brain

To investigate neural circuits and visualize expression of our target genes and proteins, we are using advanced
fluorescent microscopy techniques as well as CLARITY – optical clearing of whole brains by transformation into a transparent hydrogel matrix.

For non-invasive assessment of structural, functional and metabolic markers in living animals, we use magnetic resonance imaging
techniques including structural MRI and manganese enhanced MRI for structural or functional characterization (MEMRI).

Cell Observatory core unit (WIS)

Neuroimaging core unit (MPIP)

  
Regulation of gene expression

We are studying the regulation of stress-related gene expression both using transcriptome-wide measurements, such as microarrays and RNA-sequencing, and candidate-driven approaches like real-time PCR and in-situ hybridization.

In addition to mRNA, our lab also focuses on measuring microRNA expression – using real-time PCR and dedicated small RNA-Sequencing and in-situ hybridization protocols – and to investigate their regulatory functions, using in vitro studies, genetic mouse models and viral-based manipulations.

We also investigate how epigenetic mechanisms like DNA methylation regulate gene expression during stress, using DNA-Pyrosequencing,
traditional BS-Sequencing, TAB-Sequencing and genetic mouse models.

Along with DNA modifications, a diverse set of covalent modifications is present on mRNA. In our lab, we investigate
different RNA modifications (like m6A, m6Am, A-to-I editing) using mass spectrometry, immunoprecipitation and Next Generation Sequencing approaches.

Finally, we use quantitative proteomics (using N-15 labelling) and candidate protein measurements to investigate protein levels.

Analytics and Mass Spectrometry core unit (MPIP)

Proteomics core unit (MPIP)

Bioinformatics core unit (WIS)

Genomic core unit (WIS)

  
Measuring simple and complex mouse behavior

We use classical, standardized assays to measure mouse behavior following manipulation. These include the open field test,
elevated plus maze, dark-light box, and sucrose preference test to assay exploration, anxiety- and depression-like behaviors;
as well as cognitive assays such as object recognition, fear conditioning, Morris Water maze, water cross-maze, and five-choice serial-reaction time task.

To study a more complex behavioral repertoire, we use a novel social box system for tracking multiple animals in a rich environment,
intervention-free and across long time spans, allowing us to characterize the nature of group behavior and interactions.

Behavior and Physiology core unit (MPIP)

Social box tracking: Example video

   
Electrophysiolgy

We study the neural substrates of behavior using single-cell and neuronal network-level electrophysiology in vivo and in vitro.
Electrophysiology core unit (MPIP)

  
Telemetry, Sleep, and Physiology

Using cage-based and in vivo telemetry systems, we investigate physiological parameters (e.g. heartrate, activity, respiration, metabolic activity), and brain activity (ECG, EEG) in awake and sleeping animals.

  
Biobanks & Patient Samples

In addition to mouse models, we also study stress-related neurobiological functions directly in humans.
We collect biological samples from study participants and process them to obtain measures of DNA, RNA, miRNA, and more.
BioPrep core unit (MPIP)