Current PhD vacancies

Allergy, is an immunological hypersensitivity reaction to innocuous allergens from diverse sources, e.g. Bet v 1 in birch pollen, mediated by allergen-specific IgE. Allergen-specific immunotherapy (AIT) is the only causative treatment sustainably reducing the clinical symptoms. Allergen-specific IgG antibodies which block IgE-mediated allergic reactions are a hallmark of successful AIT. This project aims to gain insights into their repertoire, clonal complexity, specificity, affinity and effector function.

We would like to understand how the metabolic crosstalk of macrophages with tissue cells contributes to homeostatic and regenerative functions in health and disease. We investigate whether macrophages provide specific metabolites to provide a survival, proliferation, or differentiation advantage during conditions of inflammation and tissue destruction in different organoid and mouse models. In addition, we study whether the modulation of different metabolic pathways related to mTORC1 signaling mediates tissue-protective functions of macrophages.

We are looking for highly motivated Ph.D. students who are interested to perform research in the field of autoimmunity and inflammation. The project aims to investigate the role of key transcription factors for the stability and function of regulatory T cells (Treg) and to understand transcriptional and epigenetic signatures of Treg cells under inflammatory conditions. The approach entails state-of-the-art technologies, including transcriptomic and epigenomic analysis, advanced cell biology techniques as well as in vivo models.

Specific requirements:

Ph.D. candidates should hold a master's degree in molecular biology, medicine, immunobiology or a related discipline and ideally have documented experience in molecular biology, mammalian cell culture methods and mouse models. Previous experience with immunological assays, primary cell cultures, flow cytometry and bioinformatics analysis are advantageous.

The research project of this PhD aims at developing new machine learning approaches for the early detection of novel emerging diseases in large scale heterogeneous medical imaging data, and to train prediction models for individual disease course and treatment response from early scarce observational data sampled from initial routine care. Models need to detect anomalies, and deal with biases and confounders present in observational routine data. It is embedded in collaborations with Univ. Cambridge (AIX-COVNET) and the UN (ZODIAC).

The research project of this PhD aims at developing machine learning approaches that can bridge and integrate imaging data, and molecular data such as epigenomics profiling in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). Models will use the dynamics of initial imaging and molecular response to NACT for predicting response before surgery. A core novelty of the models will be the joint representation of molecular- and imaging information.

Heart disease is the main cause of death worldwide. The main underlying pathology of this devastating condition is atherosclerosis that leads to the formation of plaques in large arteries. B lymphocytes play a crucial role in the initiation and progression of atherosclerosis. The aim of the project is to identify the molecular machinery that governs the altered B cell responses in accelerated atherosclerosis, by studying transgenic mice and human tissues.

APRIL (A Proliferation Inducing Ligand) is a cytokine that is produced by many cell types in the body. Our lab discovered that APRIL plays a major protective role in atherosclerotic cardiovascular disease (Tsiantoulas et al, Nature, 2021), which is the main cause of death in the world. The aim of the project is to dissect the role of APRIL in the homeostasis of the brain-heart-immune system axis by employing integrated transcriptomic and proteomic analyses of tissues from mice and humans.

The Sitte laboratory is interested in compounds that interact with neurotransmitter transporters and receptors in a licit and illicit manner. We hypothesize that the use of agents acting to release serotonin in an exocytosis-independent manner and insensitive to autoreceptor feedback loops may act as fast-acting SERT modulators and promise therapeutic advantages over classically administered compounds to elicit serotonergic modulation. Methodologies used in the framework of the project will be biochemical tracer flux experiments, fluorescence calcium indicators for measuring receptor activity, electrophysiology and cell-toxicity assays

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a degenerative muscle disease triggered by mutations in the gene encoding for the intracellular protein dystrophin. The mechanisms responsible for arrhythmia generation, however, are largely unknown. In the planned project, we will study the so far unknown abnormalities in voltage-gated Na and Ca channel properties in dystrophic cardiac Purkinje fibers, which potentially underlie impaired ventricular conduction and arrhythmia development in DMD patients.

Population receptive field (pRF) mapping using functional magnetic resonance imaging is an ideal non-invasively approach for assessing human retinotopy in-vivo. We will develop a computational framework for obtaining quantitative measures of stimulus efficacy. Computational results will be validated by performing fMRI studies in healthy volunteer. This allows for stimulus design tailored to the specific needs in a given study and will ultimately boost clinical applicability of pRF mapping approaches.

Magnetic resonance spectroscopy (MRS) reveals quantitative time-resolved metabolic information, fully non-invasively. This project will extend the scope of ³¹P MRS beyond the oxidative regime to high exercise intensities by adding accurate quantification of muscle lactate via double-quantum filtered ¹H MRS. Intricate details of lactate detection involving structural anisotropy, compartmentation and dynamics will be investigated using a combination of MR pulse sequences, to be developed and applied at ultra-high field on our 7 T whole-body MR scanner.

Adenosine deamination by ADARs is an abundant RNA modification that converts adenosines to inosines in many metazoan RNAs. Inosines are interpreted as guanosines by cellular machineries and therefore A to I editing can change the protein coding potential of RNAs. The mRNAs encoding the actin crosslinking proteins Filamin A and Filamin B are edited at a highly conserved position leading to a Q to R exchange in an interactive region of the protein. We could previously show that lack of editing of Filamin A leads to cardiovascular problems. We now aim at understanding the regulation of this process and also look at the consequences of the editing-induced amino acid exchange in the Filamin B protein using transgenic mouse models.