NextImmune - PhD Training Program

Projects 1 and 2: Inflammatory diseases and lymphoma development

• Supervisor: Prof Dirk Brenner, 2 PhD student, 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)

Intended PhD project will be centered around the investigation of immune regulation. Our research group focuses first on how inflammation and autoimmune responses are controlled in the body’s periphery, and second, on how the same factors contribute to the development of lymphoma.

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.

For this project a PhD candidate has been recruited.

Project 3: Metabolic gatekeepers in immune cells: Decision making and controlling inflammation in vivo

• Supervisor: Prof Dirk Brenner, 1 PhD student, LIH, UL
• Research keywords: Immune regulation, Metabolism, Inflammation
• Collaborations: Johannes Meiser (LIH, Luxembourg), Karsten Hiller (University of Braunschweig, Germany)

Tight control of the immune system is crucial for a healthy body function. Imbalanced immunity can lead to detrimental diseases like systemic inflammation, autoimmunity or cancer. Inappropriate metabolic programs in activated immune cells underlie many aberrant immune responses, implying that the manipulation of the metabolism of these cells might beneficially enhance or temper immunity. In the frame of this PhD project we investigate new avenues how metabolic fluxes can be redirected in vivo and how this is associated with immunity and inflammatory diseases. It is crucial to study novel concepts of metabolic regulation in cell type- and inflammatory disease-specific in vivo contexts in order to uncover the next wave of innovative treatment options.

For this project a PhD candidate has been recruited.

Project 4: Natural killer (NK) cells in chronic lung inflammation: effectors and/or exosome releasers?

• Supervisor: Dr Jacques Zimmer, 1 PhD student, 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.

For this project a PhD candidate has been recruited.

Project 5: The role of IRG-1 in inflammatory (vascular) diseases

• Supervisor: Dr Johannes Meiser, 1 PhD student, LCSB, UL-SDU
• Research keywords: immune response gene 1, itaconic acid, inflammatory atherosclerosis inflammation, metabolism
• Cutting edge: defining a novel player as potential target mechanism for inflammatory vascular diseases
  
• Collaborations: Prof Jochen Schneider (Co-supervisor, LCSB), Dr Alessandro Michelucci (LIH), Dr Alex Skupin (LCSB)

Inflammatory vascular diseases such as atherosclerosis or vascular inflammation affect a large number of subjects of the world population. Since vascular diseases represent a lipid-driven inflammation the pathophysiology requires a rewiring of metabolism and immune system. IRG1 is a gene specifically expressed in myeloid cells upon immune system activation such as bacterial stimuli or exposure to oxLDL. The IRG-1 dependent production of the metabolite itaconic acid (ITA) directly interferes with the cellular tricarboxylic acid cycle (TCA) metabolism. IRG-1 also mediates the production and homeostasis of reactive oxygen species (ROS). These data suggest that IRG-1 links innate immune activation with metabolism. However, its role in atherosclerosis is undefined. Here, we aim to characterize the role of 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.

For this project a PhD candidate has been recruited.

Project 6: Profiling the interaction of allergens with cells of the epithelial interface

• Supervisor: Dr Christiane Hilger, 1 PhD student, 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.

For this project a PhD candidate has been recruited.

Project 7: Molecular mechanisms of chronic inflammation connected to cancer development

• Supervisor: Dr Danielle Perez Bercoff, 1 PhD student, 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 the PhD candidate will study the role of APOBEC3A, a DNA mutator, and its role in cellular transformation.

For this project a PhD candidate has been recruited.

Project 8: Proinflammatory calcium signalling and cytokine secretion in neutrophils (CASIS)

• Supervision: Prof Jean-Luc Bueb , 1 PhD student, 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, …).

For this project a PhD candidate has been recruited.

Project 9: Early-life immune programming

• Supervisor: Dr Jonathan Turner, 1 PhD student, 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 pro-graming, and to demonstrate proof of concept for the reversibility of epigenetic immune and endocrine system programming.

For this project a PhD candidate has been recruited.

Project 10: Identification of food allergens in sera of allergic and non-allergic individuals

• Junior-supervisor: Dr Annette Kuehn (main supervisor), Co-supervisor: Prof Markus Ollert, senior DTU advisor: Claude Muller, 1 PhD student, 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.

For this project a PhD candidate has been recruited.

Project 11: Dietary fiber-deprived gut microbiome in inflammatory bowel disease (IBD) and colorectal cancer (CRC)

• Supervisor : Prof Mahesh Desai, Senior mentor: Prof Markus Ollert, 1 PhD student, 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.

For this project a PhD candidate has been recruited.