Zaugg Group

Systems (epi)genetics to study the basis of complex traits and diseases

Welcome to the Zaugg Group Website!

The Zaugg Group combines genetic and epigenetic variation across individuals to study molecular mechanisms underlying complex traits and diseases. They develop and apply single cell technologies and computational tools to address basic and translational questions focused on gene regulatory mechanisms.

Previous and current research

A crucial part of precision medicine is to quantitatively understand the interplay of genetics, epigenetics, and environmental factors, including the cellular microenvironment. Given that the majority of disease-associated genetic variants lay in non-coding regions, and environmental factors often leave an epigenetic signature, we believe that gene regulatory processes are key to understand disease mechanisms. Our research highlights the emerging role of gene regulation (including enhancers and transcription factors) in disease mechanisms.

Our research vision is to understand how cells integrate genetic information, epigenetic state, and extrinsic signals from their microenvironment, and how these layers give rise to cellular states that ultimately define complex (disease) phenotypes and response to perturbations.

Our approach is to build systems biology frameworks for studying how cells respond to defined perturbations given their molecular and epigenetic profiles. For this we develop genomics technologies and computational tools to integrate data across scales and types, including single cell multiomics (RNA/ATAC), spatially resolved data and cryo-electron tomography.

Our systems of interest are: (i) the bone marrow niche, where we aim to understand how stem and progenitor cells interact with their immune and stromal microenvironment, and how these interactions contribute to hematological malignancies and therapy response. (ii) immune cells and their interaction with tissue in immune system dysfunction, inflammation, infection, and cancer. Here we are interested in understanding the cell-type specific regulatory networks that contribute to disease mechanisms.

Future projects and goals

We are expanding our work on disease mechanisms, gene regulatory networks, and cell-cell interactions along three lines of research:

  • We will integrate single cell and spatial multiomic data (e.g. from our method SUM-seq) with genetics, gene regulatory networks, and spatially resolved methods to study basic biology and translational questions focusing on the bone marrow stem cell niche and misregulation of the immune system.
  • We will harness cell-type specific gene regulatory networks to study mechanisms of primary immunodeficiencies that are caused by mutations in transcription factor genes (e.g. NFKB, STATs), e.g. within the IMMERGE consortium.
  • We will expand our data integration methods to include additional molecular layers, such as protein levels, spatial transcriptomics, multiplexed imaging, and self-supervised algorithms for electron microscopy/tomography analysis.

Examples of our methods and technologies and further reading:

Recent research highlights

Epigenetic state cell can determine a cell’s response to signalling. Adapted from Weidemüller*, Kholmatov* et (2020)
GRaNIE-inferred enhancer-mediated gene regulatory networks (eGRNs) are cell type-specific. IRF8 regulates hundreds of genes in acute myeloid leukemia (AML; left) and macrophages (right), yet only few overlap between these cell types (bottom). Adapted from Kamal*, Arnold* et al (2023)
eGRN from joint scRNA/ATAC-seq in macrophages is enriched for immune-traits. UMAP of macrophage polarisation profiled by SUM-seq (scRNA/ATAC; left), eGRN inferred with GRaNIE (right), and traits enriched in eGRN enhancers (bottom). Adapted from Lobato*, Yildiz*, Claringbould* et al (2024)
Cryo-electron tomogram segmented by DeePiCt, a supervised deep neuronal network. Adapted from de Teresa-Trueba*, Goetz* et al (2023)

Zaugg group events

Zaugg group retreat in Alsace in 2023
Testing our Ninja skills – group retreat 2023
Zaugg group retreat in Alsace in 2022
Zaugg group beer tasting in Heidelberg in 2021
Zaugg group January 2020 – Group retreat in Oberstdorf
Getting ready for the snow shoe tour – group retreat 2020
Zaugg Group October 2018 – Group Retreat in Zurich
Zaugg group October 2018 – Group Retreat in Zurich
Zaugg Group September 2017 – Group Retreat in Málaga
Zaugg Group September 2017 – Group retreat in Málaga
Zaugg Group at Bio-IT retreat March 2017 (missing Brian, Stefan and Mario)
Zaugg Group October 2015 – Group Retreat in Schwarzwald
Zaugg Group July 2015
Zaugg Group March 2015 (Ana missing)
Zaugg Group in October 2014