PhD Training Program
Individual projects - Data generation
Project 1 and 2: Inflammatory diseases and lymphoma development
- Supervisor: Prof Dirk Brenner, 2
PhDstudent, LIH, SDU-UL
- Research keywords: Inflammation, immune regulation, autoimmunity, lymphoma
- Collaborations: Tak Mak (University of Toronto), Jürgen Ruland (TUM, Munich), Philipp Lang (University of Dusseldorf), Karl Lang (Uniklinik Essen)
Protein ubiquitination, signaling to NF-ĸB and metabolic adaptations have in particular emerged as key mechanisms regulating immune homeostasis. How the differing signals triggered under various inflammatory conditions are integrated to ensure a coordinated immune response and maintenance of homeostasis is still only poorly understood. In that respect, we analyze regulatory circuits of the innate and adaptive immune system. A better understanding of how inflammatory reactions are balanced will yield novel insights into the initiation and potential treatment of inflammatory diseases and hematological malignancies.
Project 3: Natural killer (NK) cells in chronic lung inflammation: effectors and/or exosome releasers?
DrJacques Zimmer, 1 PhDstudent, LIH, UL-SDU
- Research keywords: immunology, NK cells, TAP-deficiency, exosomes
- Collaborations: Karl-Johan Malmberg (University of Oslo, Norway)
The aim of this project is to define novel pathways of antibacterial responses and cellular communication by exosomes in NK cells.
An integration of this project within the DTU is embodied through collaboration with the group of Feng He in the “Th2 response potential” project aiming to elucidate NK cell involvement and the role of NK-derived exosomes in the early innate tolerance induction phase.
Project 4: The role of IRG-1 in inflammatory (vascular) diseases
- Supervisor: Prof Jochen Schneider, 1
PhDstudent, LCSB, UL-SDU
- Research keywords: immune response gene 1, itaconic acid, inflammatory atherosclerosis inflammation, metabolism
- Collaborations: Dr Johannes Meiser (LIH), Dr Alessandro Michelucci (LIH), Dr Alex Skupin (LCSB)
Inflammatory vascular disease such as atherosclerosis or vascular inflammation affect a large number of subjects of the world population. Since vascular diseases represents a lipid-driven inflammation the pathophysiology requires a wiring of metabolism and immune system. IRG1 is a macrophage specific gene characteristic for immune system activation and is induced by bacterial stimuli as well as oxLDL. The IRG-1 dependent production of the substrate itaconic acid (ITA) directly interferes with cellular tricarboxylic cycle (TCA) metabolism. IRG-1 also mediates the production of reactive oxygen species (ROS) in macrophages. These data suggest that IRG-1 links innate immune activation with metabolism. We aim to characterize the role if IRG-1 in inflammatory vascular disease in vivo and in vitro. This project aims at defining a novel player as potential target mechanism for inflammatory processes in the vasculature.
Project 5: Profiling the interaction of allergens with cells of the epithelial interface
DrChristiane Hilger, 1 PhDstudent, LIH, SDU-UL
- Research keywords: allergy, animal allergens
- Collaborations: Dr Gunnar Dittmar (LIH), Dr Paulette Charlier (CIP, Liège), Dr Martine Morisset (CHL, Luxembourg)
Mechanisms of cellular binding, uptake, processing and presumed allergenic immune modulation of animal allergens are not fully characterized yet. The elucidation of cellular pathways induced by animal allergens is crucial for the understanding of allergic immune responses to animals and may ultimately lead to new therapeutic approaches.
Project 6: Molecular mechanisms of chronic inflammation connected to cancer development
DrDanielle Perez Bercoff, 1 PhDstudent, LIH, UL-SDU
- Research keywords: chronic viral infections, chronic inflammation, cancer, DNA mutators, IFN-stimulated genes
- Collaborations: Simon Wain-Hobson (Pasteur Institute, Paris)
Chronic inflammation is a major driver of cancer development. However, with certain exceptions (ROS, NF-κB) the molecular mechanisms linking inflammation to cancer development remain elusive. In this
Project 7: Proinflammatory calcium
signalling and cytokine secretion in neutrophils (CASIS)
- Supervision: Prof Jean-Luc
Bueb ,1 PhDstudent, LSRU, UL
- Research keywords: inflammation, neutrophils, calcium
signalling, cytokines, secretory granules.
According to recent advances, neutrophil-derived cytokine secretion and degranulation may play a major role in the development and resolution of inflammatory responses.
In this project, we aim at deciphering the role of Ca2+ in cellular granule processing and cytokine secretion. Experiments will be done on human (and possibly mouse) neutrophils and cell lines, in healthy and pathological inflammatory situations, under stimulated/modulated conditions (LPS, fMLF/2-APB, BAPTA, ...), in order to identify the cellular mechanisms leading to chronic inflammatory diseases (rheumatoid arthritis, cancer-related inflammation, …).
Project 8: Early-life immune programming
DrJonathan Turner, 1 PhDstudent, LIH, UL-SDU
- Research keywords: epigenetics, early life programming, stress
- Collaborations: Prof Wim Vanden Berghe (University of Antwerp, Belgium)
This project is based on inducing immune- and HPA axis phenotypes after early life environmental exposures that are known to significantly increase the risk of disease later in life, and examining the underlying epigenetic mechanisms, identifying potential classifying biomarkers, The goals of this project are twofold: determining the mechanisms underlying the lifelong immune
Project 9: Identification of food allergens in sera of allergic and non-allergic individuals
DrAnnette Kuehn (main supervisor), Co-supervisor: Prof Markus Ollert, senior DTU advisor: Claude Muller, 1 PhDstudent, LIH, SDU-UL
- Research keywords: food allergy, allergen processing, oral tolerance
- Collaborations: Carsten Bindslev-Jensen (Odense, Denmark), Yeoun Jin Kim (LIH)
The present project aims at identifying digestion-resistant peptides of food allergens, which are circulating in the bloodstream of healthy and allergic individuals. One main target of the present project is the development of a method for peptide analysis of food allergens in sera of healthy/allergic individuals.
This project covers NextImmune areas A and C.
Project 10: Dietary fiber-deprived gut microbiome in inflammatory bowel disease (IBD) and colorectal cancer (CRC)
Supervisor :Prof Mahesh Desai, Senior mentor: Prof Markus Ollert, 1 PhDstudent, LIH, UL-SDU
- Research keywords: Inflammatory bowel disease (IBD), colorectal cancer (CRC), dietary fiber, gut microbiome, colonic mucus layer
Collaborations :Prof Markus Ollert, Luxembourg Institute of Health, Luxembourg, Prof Eric Martens, University of Michigan, USA, Prof Gabriel Nunez, University of Michigan, USA
The project seeks to understand how a fiber-deprived gut microbiome impacts our health.
The modern diet of developed nations includes significantly reduced dietary fiber, which is thought to contribute to recently increased cases of inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, little is known about the gut microbiota-mediated mechanisms that connect diet to these diseases. Using gnotobiotic mouse models containing characterized human gut bacterial communities, we have recently shown that a gut microbiota deprived of dietary fiber increasingly forages on the protective colonic mucus barrier, thereby enhancing susceptibility to gastrointestinal pathogens. The current project aims to understand the role of a dietary fiber-deprived gut microbiota in driving pathogenesis of IBD and CRC. The project offers exciting training opportunities for an early-career scientist and will involve: samples from human subjects; work with mouse models; collaborations with clinicians/scientists at the international level; basic and applied aspects; and usage of state-of-the-art techniques in microbiology/immunology.
- Area A: Data generation
- Area B: Computational analysis
- Area C: Validation and pre-clinical target evaluation
For any question related to NextImmune, please contact:
Prof Markus Ollert