Projects will be added as they appear, latest until 20.02.23, so please check the Projects section for your preference. Do not submit your application until you have selected a project list.

Carolin Daniel, Prof. Dr. phil. nat.

Type 1 Diabetes Immunology (TDI)

Immune Tolerance in Diabetes 

Project Description 

The role of metabolic endocrine signaling for regulatory T cell induction and 
function in diabetes 

Obesity and Type 2 Diabetes Meletus (T2DM) are accompanied by the chronic low-grade inflammation in tissues and organs, which drives the development of insulin resistance and other obesity-associated comorbidities. In a heathy state this inflammation is constrained by a specialized population of regulatory T cells (Tregs), which highly populate these tissues, supporting the local immunometabolic cross-talk and homeostasis. Upon obesity, the phenotype, stability and functionality of these tissue Tregs are disturbed, which leads to a strong reduction of this population, outbreak of chronic low-grade inflammation and impaired systemic metabolism. We, therefore, intensively study the molecular mechanisms of Treg tissue adaptation and maintenance, with a vision for developing strategies to target these Tregs to restore immunometabolic homeostasis. 

In frame of this project you will support us investigating the impact of the endocrine hormone signaling on tissue Tregs. You will learn and perform the isolation and phenotyping of T cells and Tregs from various murine tissues using flow cytometry and other molecular biology methods (PCR/qPCR, histology, ELISA). Additionally, you will be having the chance to learn the basics of maintenance of laboratory animals’ cohorts, data analysis and statistical methods, as well as to participate our weekly meetings with scientific discussions about the recent findings in the field of immunology and immunometabolism.     

Timo Müller, PD Dr. rer. nat.

Institute for Diabetes and Obesity

Molecular Pharmacology

Project Description

Our group works on the development of novel Pharmacotherapies for the treatment of obesity, type 2 diabetes and its complications, such as fatty liver disease and atherosclerosis. Together with our collaboration partners from the industry (Novo Nordisk), we have generated a set of new biochemically modified analogs at the receptor for the glucagon-like peptide-1 (GLP-1), which we will within this project screen for their in vitro ability to affect GLP-1 receptor (GLP-1R) signaling. The studies include a series of BRET-based in vitro assays to determine functional binding and signaling via GLP-1R, including ligand-induced cAMP production, GLP-1R internalization and recycling and signaling with Gq G protein-coupled signaling. The most successful candidates will subsequently be evaluated in vivo in diet-induced obese for their potential to affect body weight, food intake, glucose metabolism, as well as cholesterol- and lipid metabolism. 

Prof. Paul Pfluger, Prof. Dr. rer. nat.

Institute for Diabetes and Obesity

Research Unit NeuroBiology of Diabetes (NBD)

Project Description

Spatial and functional characterization of hypothalamic leptin target genes

Obesity and its comorbid sequelae are major health burdens across European nations. Many citizens would greatly benefit from permanent weight loss, but only a few succeed. They rather suffer from weight regain after dieting, often referred to as Yoyo effect. Delineating the largely unexplored, CNS-driven molecular events that impede sustainable weight loss and drive the Yoyo effect is a prerequisite for future therapies, and a major goal of this internship.

In the past, my lab demonstrated unprecedented weight loss in diet-induced obese mice treated with the plant-derived leptin sensitizer celastrol. Our data suggested breakthrough potential for therapeutic anti-obesity strategies built upon hypothalamic leptin re-sensitization, and pointed towards a key role for orexigenic circuitry residing in the hypothalamus. As key objective for this summer internship, we will delineate the functional role of newly identified genes on leptin resistance and leptin re-sensitization in key subpopulations of hypothalamic neurons. First, using a hypothalamic cellular model, the student will manipulate selected genes using Crispr-Cas9-mediated gene editing and conduct proteome as well as transcriptome analyses to study leptin signalling. Second, using hypothalamic cryo-slices of reporter mice subjected to dietary and pharmacological weight loss interventions and techniques such as RNAscope and confocal microscopy, the student will assess the cellular distribution and the relative expression of the same genes in hypothalamic neurons. Within the 2-months research stay, the student will be implemented into a team of international scientists, with direct supervision and training by PhD students and senior scientists.

Dr. Teresa Rodriguez-Calvo (DVM, PhD)

Institute of Diabetes Research, IDF1 

Type 1 Diabetes Pathology 

Project Description

Characterization of the epithelium and gut associated lymphoid tissue in human type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune condition, which is primarily diagnosed when an individual presents with hyperglycaemia and an absolute requirement for the provision of exogenous insulin to regulate blood glucose. For several systemic autoimmune and metabolic diseases, the mechanisms of tissue damage and immune regulation include epithelial barrier defects and microbial dysbiosis. A number of studies suggest that a leaky gut could be an initiator of T1D, where the activation of pathogenic immune cells in the gut can lead to their migration to the affected organs. Notably, epithelial barriers are also regulated by metabolic mechanisms, for example, high tissue glucose concentrations can negatively affect the tightness of epithelial barriers. Therefore, there is a growing appreciation of the interplay between mucosal immunity, immune homeostasis, the microbiome, and the development of T1D. Alterations in the composition and diversity of the microbial populations in the gut have been observed in cohorts of individuals who go on to develop T1D. Reduced integrity of the gut barrier is also observed in pre- and recently diagnosed diabetics. This project aims to test the hypothesis that perturbations in the mucosal immune system are related to the development of T1D. The selected student will investigate whether the gut associated lymphoid tissue (GALT) is abnormal in individuals with the disease compared to non-diabetic individuals. For this, she/he will use human tissue samples obtained from the network of Pancreatic Organ Donors with Diabetes (nPOD) biobank.

Aims: To assess the structure and integrity of the intestinal epithelial layer and gut associated lymphoid tissue (GALT) in the duodenum of individuals with T1D using multiplexed immunofluorescence and state of the art imaging and image analysis.

The student will learn immunofluorescence techniques (wet lab) and will have the opportunity to work with/on:

• Brightfield/fluorescence microscopy

• Confocal/high-resolution microscopy

• Emerging state-of-the-art quantitative imaging solutions.

• Image analysis/quantification

• Statistical analysis of data

• Scientific writing

This opportunity will interest someone with a curious mind, a clear interest in laboratory research, but also interested in learning how to utilize big data sets to answer important questions in human pathologies.

Dr. Sonja C. Schriever 

Institute for Diabetes and Obesity

Research Unit NeuroBiology of Diabetes (NBD)

Project Description:

In vitro characterization of novel regulators of hepatic steatosis in obesity

Obesity-induced ectopic fat disposition in the liver is a major risk factor in the pathogenesis of hepatic insulin resistance and type 2 diabetes. Treatment of hepatic steatosis is largely based upon calorie restriction or exercise to facilitate substantial weight loss. Delineating the molecular underpinnings of novel, translationally relevant gene regulators of obesity-related hepatic steatosis and CR-induced hepatic lipid clearance can advance our search for novel, drugable targets.

We recently developed a correlation-based network integration (CoNI) approach, a bioinformatical tool for the (re-)assessment of existing transcriptome, proteome and metabolome data that allows to unravel previously hidden local controlling genes (LCG) that exert major changes to hepatic metabolite levels.

As key objective for this summer internship, we will investigate the functional role of the newly identified genes in the etiology and reversal of hepatic steatosis in mice and men. Using a murine hepatic cellular model, the student will apply Crispr-Cas9-mediated gene editing to manipulate selected genes to then analyse their effect on hepatic insulin and glucose metabolism at the protein and gene level. Second, using immunofluorescence techniques and triglyceride uptake assays, the student will assess the cellular distribution and the effect of the same genes on hepatic lipid metabolism. Last, the student will investigate whether the targets of interest are regulated in mice subjected to dietary and pharmacological weight loss treatments. The student will be implemented into a team of international scientists, with direct supervision by PhD students and senior scientists.

Dr. Anastasia Georgiadi

Institute for Diabetes and Cancer

Endocrine Pharmacology

Project Description:

Sex/gender differences and adipose tissue function

In my lab we are interested to understand the complexity of the human adipose tissue and its role as an endocrine organ. Men and women have many differences in adipose tissue distribution and function. It has been proposed that the ability of women to store excess fat subcutaneously rather than viscerally partly accounts for their lower risk (compared to males) for death due to cardiovascular complications. In addition, women have a greater amount of thermogenic, brown adipose tissue, which has been associated by itself with lower risk of death from cardiovascular diseases. There are differences in mitochondrial energetics, transcription rates of many mitochondrial genes and also mitochondrial cristae and density between males and females. These differences have been reported for brown and white adipocytes, whereas is less is known for other adipose tissue cell types. There is a lack of cellular models that can be used to understand sex differences at the cellular and molecular level. The lack of immortalized female cell lines of adipose tissue cell types hinders such studies.

The main goal of the summer internship will be to support us in the functional and molecular characterization of newly generated (in our lab) adipocyte mouse and human female immortalized cell lines. We will run different molecular assays on these cells in order to understand: a) their differentiation/adipogenic capacity, b) lipid storage capacity, c) responsiveness to feeding and fasting hormones, such as insulin, glucagon, cortisol, d) response to thermogenic and lipolytic signals, such as beta-adrenergic receptor ligands. In addition, e) we will characterize their mitochondrial function by Seahorse methods-based protocols to assess mitochondrial respiration and f) substrate preferences.