Systems biology of immune cells

We are interested in how environmental contaminants modulate the immune system with focus on the analysis of the cellular transcriptome, proteome and metabolome in health and disease.

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:

Nanomaterial effects on macrophage biology
People in industrialized countries are increasingly exposed to various engineered nanomaterials (NMs) due to their wide application in e.g. medicine, cosmetics, building materials or packaging, and the continuous development of novel NMs. Thus, we aim to
The impact of pollutants on aryl hydrocarbon receptor signalling in macrophages
The Aryl hydrocarbon receptor (AhR) has a regulatory role in immunity. It provides either pro- or anti-inflammatory signals, depending on the specific ligand and cell type. On the one hand, AhR interaction partners in macrophages are investigated by means of affinity-purification MS (AP-MS). On the other hand, AhR-dependent, ubiquitin-mediated signalling processes are investigated utilizing global ubiquitome and proteome approaches.
more: Henning Großkopf
Characterization of glycosaminoglycans-effects in cellular models
In this project within the Transregio 67 research consortium, cellular adaptions to GAG-treatment in terms of altered protein expression or activity of specific signaling pathways are investigated utilizing mass spectrometry-based, quantitative proteomics, and phosphoproteomics. A special focus is on the identification of novel GAG-interacting proteins by means of affinity-purification MS (AP-MS). Additionally, we aim to characterise effects of artificial GAGs in human macrophages.
more:  Henning Großkopf; Transregio 67

Systems biology of specialized T cells

Mucosal-associated invariant T (MAIT) cells are an evolutionary conserved subset of specialized, innate-like T cells found in mammals. MAIT cells are unique in their ability to recognized bacterial metabolites, and are considered to have key roles in immunity, but also in the pathogenesis of diverse inflammatory diseases. It was recently shown, that MAIT cell function can be modulated by drugs and drug-like molecules. Hence, we aim to characterise the molecular effects of chemicals in MAIT cell biology on the transcriptome, proteome and metabolome level.

Impact of environmental contaminants on the development of obesity and -associated inflammation

According to the World Health Organisation (WHO) the percentage of people suffering from overweight has more than tripled since the 1970s. Unhealthy overweight (obesity) is one of the major risk factor, in children and adults, for the development of metabolic disorders like diabetes, cardiovascular diseases, hypertension or fatty liver disease. In previously studies it could be shown that environmental factors like phthalates promote the development of obesity. Understanding the underlying pathophysiological mechanisms is essential for the design of new prevention strategies and more effective treatment procedures for obese patients.

Adipokine Profiling
In this project, we aim to establish a mass spectrometry-based assay for the simultaneous identification and quantification of > 30 adipokines and apolipoproteins in human serum and tissue samples. Furthermore, metabolites in human tissue and serum will analyzed. The overall goal is to investigate the impact of environmental factors on adipokine and metabolite levels and correlate these to clinical parameters and obesity-related comorbidities.
more: Laura Krieg; SFB1052
Molecular interactions of phthalates with PPARγ in obesity
The pathogenesis of obesity and -related comorbidities has been shown to be affected by environmental factors. Particularly plasticizers can drive obesogenic effects. Plasticizers can disrupt endocrine functions, like the differentiation of adipocytes in adipose tissue. This process is substantially controlled by the peroxisome proliferator-activated receptor γ (PPARγ). In the last years it was reported that besides binding of natural ligands like prostaglandin, a number of phthalates from the group of plasticizers are able to activate the PPARγ. By processing in consumer-related plastic products, plasticizers are ubiquitary distributed in the environment, which may affect humans as well as aquatic organisms. To overcome the artificial separation of human and ecological toxicology, the molecular interactions underlying the obesogenic and therefore health-damaging effects of plasticizers in humans and zebrafish will be investigated.
more: Alexandra Schaffert; DBU