Toxicoproteomics group - Research topics

In children, adolescents and adults, obesity is the greatest risk factor for the development of metabolic diseases such as diabetes, cardiovascular diseases, high blood pressure, non-alcoholic fatty liver, and certain types of cancer. Metabolism-disrupting chemicals (MDCs) have been linked to the development of obesity and associated diseases. Understanding the underlying pathophysiological mechanisms is essential to develop preventive measures and effective treatment methods for patients with obesity.

In adipose tissue, in particular the function of adipocytes can be affected by MDCs. Due to the low-grade inflammation in adipose tissue associated with obesity, which is primarily mediated by macrophages, these cells are considered key factors in characterizing the effects of metabolic disrupting chemicals (MDCs). However, how MDCs influence the interaction of both cell types is still unclear.

Our projects aim to gain a mechanistic understanding of the effects of MDCs on adipogenesis and on the interplay between adipocytes and macrophages and their functions. Using innovative systems biology omics methods, such as bulk and single cell proteomics, thermal proteome profiling or the analysis of post-translational modifications, molecular initiation events and key events are identified, which provide data for the development of an adverse outcome pathway (AOP). In addition to deciphering the mode of action of MDCs, our research defines molecular signatures that explain the effects of MDCs and provide biomarkers for human biomonitoring.


We are working on following research topics:

Effects of environmental contaminants on macrophage biology

Monocytes and Macrophages, cells of the innate immune system, built the first line of defense in immunity. Several studies could clearly indicate adverse effects of environmental contaminants in human monocytes and macrophages, e.g. the development of oxidative stress, mitochondrial damage or the induction of inflammatory processes. However, the underlying mechanisms, e.g. direct effects on the proteome or metabolome, have not been well characterized yet. 

Hence, we are interested in investigating the influence of pollutants such as nanomaterials, micro- and nanoplastics, plasticisers, preservatives or polycyclic aromatic hydrocarbons in acute inflammatory processes. In addition to classical molecular biological methods, we use global proteomics in combination with the analysis of post-translational modifications (phosphorylation, acetylation and oxidation).

More informations: Stefanie Raps


Effects of environmental contaminants in adipocytes

In previous work we were able to show that adipogenesis and the function of adipocytes is altered by environmental chemicals such as plasticisers. To better understand the molecular mechanisms of action of such environmental chemicals, we use global proteomics in combination with the analysis of post-translational modifications (phosphorylation, acetylation and oxidation) in addition to classical molecular biological methods.

Post-translational modifications (PTMs)

Within the DFG Collaborative Research Centre 1052 "Mechanisms of Obesity" we use mass spectrometry-based methods to characterise post-translational modifications (acetylation and phosphorylation) during adipogenesis and in mature adipocytes. How environmental chemicals modify PTMs and resulting functional consequences is also a goal of our work.

more information: Alix S. Aldehoff CRC1052 Graphical Abstract

Adipogenesis as a new endpoint in risk assessment

As part of the European Partnership for the Risk Assessment of Chemicals ( PARC ), we establish a novel approach method for adipogenesis as an endpoint in risk assessment. Molecular effects and cellular target proteins of little-studied bisphenol A alternatives are characterised by global proteomics and thermal proteome profiling.

more information: Jasmin Kleißen


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proteomicsr: An analysis pipeline for label-based and label-free proteomics data
Creator: Karkossa, Isabel

Description
This package summarizes helpful functions to analyze global information on protein abundance (proteomics) and the abundance of post-translational modifications (PTMs), referred to as PTM-omics. Thereby, it supports data from label-free and label-based approaches. For this purpose, functions for initial data evaluation and clean-up, data transformation, determination of significantly affected candidates, and different typically presented proteomics plots are provided. Furthermore, it contains functions to perform enrichment analyses as well as to visualize significantly enriched terms as well as candidates assigned to such terms. Enrichment analyses are performed based on gene sets of the MSigDB, but also the visualization of results obtained using the Ingenuity Pathway Analysis (IPA, Qiagen) tool is possible. Last but not least, the steps necessary to perform a Weighted Gene Correlation Network Analysis (WGCNA) are included, starting with the network creation and finally exporting potential key drivers of the effects (so-called hub genes).

Although this package has been established for proteomics data, it works (in parts) for other omics layers as well. For instance, the determination of significantly altered candidates can be applied to metabolomics data, the enrichment using MSigDB gene sets can be applied to transcriptomics data, and the WGCNA is applicable to all omics layers, even for integrative data evaluation.

The current version is available on zenodo or git:
zenodo git