Fröhlich Lab - Proteomics

Proteomic characterization of animal disease models for molecular biomedical research

Advances in modern mass spectrometry-based proteomics in sensitivity, specificity and throughput have allowed proteomics to become an established part of translational biomedical research. In discovery proteomics experiments, body fluids and tissues are commonly used to investigate pathological mechanisms and to search for novel therapeutic targets and biomarkers.
For reasons of effectiveness and to test novel therapeutic approaches, suitable animal models are of decisive importance in translational biomedical research projects. Pigs share many anatomical and physiological characteristics with humans and, in this regard, represent an instructive model for studying diabetes and obesity as well as rare monogenic diseases such as muscular dystrophy. Using quantitative state-of-the-art proteomics to analyze transgenic pig models created in LAFUGAs “Model organisms” unit, we complement basic pathological findings with high throughput data for an improved understanding of molecular pathology. Besides new functional insights, we aim to detect disease specific protein markers as well as protein target candidates for diagnostic and therapeutic applications.

Ongoing research includes:

• Proteomic characterization of long-term diabetic INSC94Y transgenic pigs as a model of mutant INS gene-induced diabetes of youth (MIDY)
  The Munich MIDY Pig Biobank, hosted at the Institute of Veterinary Pathology at the Centre for Clinical Veterinary Medicine of the LMU Munich, offers a unique resource for studying organ crosstalk in diabetes (Blutke et al., 2017). The close cooperation of the LAFUGA research units Proteomics (Thomas Fröhlich), Genomics (Helmut Blum) and Model Organisms (Eckhard Wolf) facilitates a “multi-omics – multi-tissue” approach to study consequences of chronic insulin insufficiency and hyperglycemia.

• Proteome studies on a tailored pig model for Duchenne muscular dystrophy (DMD)
  Duchenne muscular dystrophy is a genetic disorder caused by deficiency of dystrophin and leads to severe progressive muscle degeneration and weakness. It is diagnosed in approximately 1 in 3600 live male births usually around the age of five and, without intervention, ultimately leads to death at a mean age around 19 years. In a proteome analysis of skeletal muscle samples from a DMD pig model, we could detect stage-specific proteome changes correlated with progression of disease, thus providing readouts for monitoring of molecular effects of treatment trials (Frohlich et al., 2016). Currently, the proteome analysis is extended to heart muscle and diaphragm.