Research Funding of the Institute of Innate Immunity

Excellence Cluster ImmunoSensation2

ImmunoSensation2 is a DFG-funded Cluster of Excellence dedicated to investigating innate immunity beyond the boundaries of classical immunology, which we term the immune sensory system. Our scientists include immunologists, neurobiologists, system biologists and mathematicians from University of Bonn Medical Faculty and Faculty of Mathematics and Natural Sciences and the German Center for Neurodegenerative Diseases (DZNE) of the Helmholtz-Society.Founded in 2012, ImmunoSensation is currently in its ninth year of funding, and we continue to pursue our mission of innovative science in immunology, with a focus on connecting immunology to other systems, such as the metabolic system and the nervous system, and better understanding the intimate connection between the immune sensory system and human health and disease.‍

DFG Förderung zusammen mit National Science Foundation (NSE) Projekt

Cellular communication is crucial for cell differentiation, tissue development and function. Chemical and protein cues are key signaling molecules for cell communication and a slender protrusion from the surface of the cell body, called the primary cilium, acts as a cellular antenna that receives extracellular cues and transduces this information into the cell body. The biggest challenge in understanding how cilia receive signals from the environment is that the small cilium is challenging to functionally or physically isolate. In turn, distinguishing what is happening within the cilium versus the cell body is murky. Genetic ablation of cilia abolishes all ciliary signaling, making it impossible to dissect ciliary-specific signaling pathways. Cyclic AMP (cAMP) is a central messenger for ciliary signaling. However, how the cell distinguishes between ciliary and cytoplasmic cAMP signaling outputs and which signaling pathways and cellular cues are specifically engaged by ciliary cAMP signaling is not known. The Wachten and Mick labs have recently shown that chronic stimulation of ciliary cAMP signaling controls epithelial cell remodeling. Recent data from the Caspary lab indicates that loss of ciliary ARL13B, by introducing a mutation that inhibits transport of ARL13B to the cilium, shows striking similarities to chronic ciliary cAMP stimulation. Here, we hypothesize that ARL13B in the cilium defines the ciliary cAMP compartment and that loss of ARL13B in the cilium increases ciliary cAMP levels that, in turn, changes epithelial cell polarity and morphology. To test this hypothesis, we will apply genetically-encoded biosensors and optogenetic tools in genetically modified, renal epithelial cells lacking ciliary ARL13B and combine this approach with spatial proteomics in the cilium to unravel how ARL13B controls ciliary cAMP signaling and epithelial cell remodeling. The outcome of our work will contribute to the understanding of how compartmentalized signaling in primary cilia controls cellular signaling and function.

Emmy Noether Programme

FOR 2743

The cells and tissues of our body are constantly subjected to stress resulting from mechanical forces. Skeletal muscles and heart generate such forces. Skin and bones have to withstand them. The kidney filtrates our blood under constant mechanical stress resulting from the blood pressure. And even the migration of cells for example during immune defence or tumour invasion is influenced by mechanical forces. The research unit investigates how cells and tissues cope with mechanical stress.

FOR 5547

Primary cilia are important regulators of adipose tissue development and function. White adipose tissue (WAT), which stores energy as lipids and is vital for maintaining whole-body energy and immune homeostasis, relies on primary cilia function. This is underlined by a subset of ciliopathies, disorders that arise from cilia dysfunction, which display obesity as a cardinal feature. The differentiation into adipocytes, termed adipogenesis, is highly orchestrated: precursor cells first commit to the adipocyte lineage and then terminally differentiate into adipocytes. Primary cilia are present on pre-adipocytes but are disassembled during proliferation and differentiation. Strikingly, loss of primary cilia formation in pre-adipocytes abolishes differentiation, underlining the importance of primary cilia function for WAT development. However, the stimuli controlling primary cilia signaling and, thereby, pre-adipocyte proliferation and differentiation are largely unknown. Macrophages, one of the major immune cell types in WAT, can influence adipogenesis and contribute to obesity-associated comorbidities. WAT-resident macrophages produce the growth factor PDGFcc, which is required for adipogenesis during development and upon diet-induced obesity. Intriguingly, PDGFs, including PDGFcc, exert their actions via the primary cilium. However, whether macrophage-derived PDGFcc in WAT acts via primary cilia on pre-adipocytes is not known. In this project, we use 2D and 3D cell culture systems in combination with transgenic mouse models to address how signals derived from macrophages affect ciliary protein dynamics and signaling in adipocyte precursors and how this shapes cell fate and function and, thereby, WAT development and homeostasis.

Gottfried Wilhelm Leibniz-Preis

IRTG 2168

Bonn & Melbourne Research and Graduate School Immunosciences

SFB 1123

Our data provide evidence that the inflammasome members Nlrp3 and Nlrp6 promote opposing functions in atherogenesis. We found that NLRP3 serves as “early sensor” for high fat western diet (WD) and initiates epigenetic changes and advanced onset of atherosclerotic disease, whereas NLRP6 protects the host, possibly by maintaining intestinal immune homeostasis. Here, we aim at identifying active NLRP3 and NLRP6 inflammasomes during WD (Aim 1), metabolic evaluation of the gut-liver-atheroma axis in a hypercholesteremic environment (Aim 2), and deciphering NLRP6-based influences on the epigenetic landscape in the early onset of atherosclerotic disease (Aim 3).

SFB 1335

SFB 1403

SFB 1454

SFB 914

SFB TRR 237

SFB TRR 249

The TRR259 is a Collaborative Research Center funded by the German Research Foundation (DFG) at the University Bonn, Cologne, and Düsseldorf. In a joint and multidisciplinary effort, we are investigating the molecular and cellular mechanisms of aortic disease holistically, with a particular focus on aortic valve stenosis, aortic aneurysm, and aortic dissection. Prospectively, we envision identifying novel pharmacological, interventional, and surgical targets for diagnostic, preventive, and therapeutic strategies within the frame of translational and clinical studies

SFB TRR 274

SFB TRR 333

The CRC/TRR research program is divided into 19 projects, each one focusing on a different aspect within the metabolism of brown adipose tissue. Every partner has its own special field of expertise and is an adept in the use of certain technologies. By combining these abilities, excellent research on the field of brown and beige fat tissue is realised.

SFB TRR 83

Biological membranes with their two key constituents - proteins and lipids - mediate an astonishing array of functions ranging from simple barriers to complex signal transduction platforms. In contrast to an aqueous solution, where protein interactions are controlled by a single solvent - water -, lipid bilayers contain hundreds of different acyl chains and head groups providing distinct amphipathic interfaces and thus open another dimension to create architectural and functional diversity. The central aims of the TRR 83 are to characterize the molecular composition and structural organization of distinct membrane domains, to elucidate their physical and chemical properties and to understand their physiological functions. The TRR 83 joins scientists from three locations – Bonn, Dresden, and Heidelberg – and has significantly advanced the current status in lipid analysis, lipid imaging, and lipid cross-linking by developing various new chemical tools.

SPP 1726

The aim of the priority programme is to coherently combine the research activities on microswimmers in biology, biophysics, theoretical and experimental soft matter physics, and simulation sciences. Advanced experimental techniques, new nanotechnological tools, soft-matter chemistry and physics, and novel simulation approaches promise deeper insights into the underlying physical and bio-chemical processes, and provide the tools to design and construct new artificial microswimmers.

SPP 1923

Retroviruses comprise a diverse group of exogenous and endogenous viruses defined by their unique replication strategy to reverse-transcribe their RNA genome into a complementary DNA. Millions of years of coevolution with their mammalian hosts gave rise to highly pathogenic as well as apathogenic members of this family of viruses and to species-specific differences in their pathologic potential. Evidence is emerging that cell-type specific cell-autonomous components of the innate immune system, including specialized pattern recognition receptors and broadly active antiviral restriction factors, represent key determinants of the fundamentally different outcomes of retroviral infections. However, the specific host cell machineries involved in recognizing retroviral infection, viral evasion strategies thereof, and their relative contribution to retroviral pathogenesis in specific target cells and organs remain to be defined. Priority Program SPP1923 (Innate sensing of restriction of retroviruses) thus aims at the identification of the full molecular sensing and restriction machinery involved in cell-autonomous immunity against retroviruses, its regulation, virus-encoded countermeasures, and pathophysiological consequences. During the first funding period of SPP1923, a strong collaborative research and training network of retrovirologists and innate immunologists was developed that defined novel important molecular mechanisms and cell-type or species-specific principles of retroviral sensing and restriction of retroviruses. Work during the second funding period will build on these findings and the interdisciplinary network established with the goal to gain detailed molecular and physiological understanding of these processes. Central funds are requested for an SPP office that assists the SPP coordinator in managing SPP activities and for networking activities such as SPP internal meetings, workshops, exchange of co-workers and an international SPP conference.

SPP 1926

In recent years, optogenetics revolutionized research in neuroscience and is now transforming also cell biology. Genetically encoded or addressable, light-controlled proteins or molecules are introduced in heterologous cells, tissue or whole animals to enable temporally precise and largely non-invasive control of molecular, cellular, or network activities.

Walter Benjamin-Programm

ZIM Förderung

Entwicklung einer innovativen Technologie zur optogenetischen Prozesssteuerung in der Biopharmazeutika-Produktion Teilprojekt: Neuartiges optogenetisches Expressionssystem (OPTO Express)

BMBF CTAP

BMBF-Wissenschaft im Dialog

COVIMMUNE

In this consortium clinicians involved in COVID-19 patient care at the University Hospital Bonn work together with basic scientists with expertise in immunology from the Medical Faculty of the University of Bonn to achieve a better understanding of the divergent host responses to SARS-CoV-2 infection. In three interconnected subprojects COVIMMUNE will perform a systems approach to assess how the cellular and humoral innate and adaptive immune responses to SARS-Cov-2 infection contribute to the immediate and long-term clinical outcome of COVID-19. The consortium has access to large pre-existing and prospective cohorts of patients with asymptomatic, mild and severe COVID-19 disease and through longitudinal profiling of the immune response will be able to mechanistically link the immune response to the clinical outcome of the disease.

ERC Consolidator Grant

https://cordis.europa.eu/project/id/101044133 Inflammation is a natural mechanism to restore tissue homeostasis, and its deregulation causes human disease. The programmed cell death form pyroptosis elicits inflammation in a cell-autonomous and non-autonomous fashion by releasing cytokines and ‘danger’ signals. Intriguingly, immune pathology independent of cytokines has alluded to unexplored signaling circuits between cells regulating pyroptotic inflammatory reactions. FIREALARM addresses the fundamental question of the physiological origin of inflammation using convergent system-wide, organismal, cell biological, and molecular approaches. We will test the central hypothesis that endogenous intercellular signaling proteins drive sterile inflammation and shift homeostatic stable to non-resolving chronic states. We will determine paracrine activities of pyroptosis by systematic, iterative ablation of molecule release from dying and perception pathways of sentinel cells. In a complementary approach, we will identify inflammatory signals in vitro and in vivo by newly developed cell type-specific mass spectrometry-based secretomics technologies. Holistic views of intercellular signaling proteins, their exposure, and modification will determine the molecular language orchestrating communication networks between cells and enable the recognition of signals initiating, amplifying, and resolving inflammation. We will achieve a new level of molecular and organismal understanding of intercellular circuits governing homeostasis and conceive strategies to revert chronic conditions. Emerging inflammatory cell death markers will stratify molecular etiology and outcome of patients with sterile inflammatory diseases. Together, FIREALARM tackles the fundamental principles of sterile inflammation relevant for understanding the pathogenesis of chronic metabolic and age-related disorders.

ERC Consolidator Grant

ERC Consolidator grant

ERC starting grant

ERC-2023-POC

In our ERC-funded, we will test the ability of nanobodies to erase memories from previous inflammatory events and prevent hyper-inflammation.

GIF

Horizon 2020 research and innovation programme

Depression is highly associated with cardiovascular disease (CVD), significantly increasing the risk of CVD development, acute events and mortality, especially in women. As a consequence, it represents a social and economic issue affecting the patient’s life and causing healthcare costs to rise. However, the mechanisms and progression of the disease remain unknown. The EU-funded TO_AITION project works on the hypothesis that immune-metabolic dysregulation due to genetic, lifestyle and environmental risk factors affects immunity mechanisms leading to CVD-associated depression. The project will effectuate basic, preclinical and clinical research applying data-driven strategies to detect and describe immune-metabolic mechanisms responsible for CVD-depression comorbidity, aiming to improve diagnosis and management of the disease.

Gemeinnützige Hertie Stiftung

Alzheimer Forschung Initiative

Boehringer Ingelheim Fonds

Chad Tough Foundation

Deutsche Demenzhilfe

EFSD/ Boehringer Ingelheim

Else Kröner-Fresenius-Stiftung

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common hereditary disease worldwide. ADPKD belongs to disorders, which are commonly referred to as ciliopathies. Ciliopathies are due to defects in tiny structures – the primary cilia. Primary cilia are eyelash protrusion emanating from the cell surface that function as cellular antenna. Defects in this antenna function in the kidney cause cyst development. However, the molecular details how the antenna function is disturbed and why this leads to cyst development, is not well understood. Here, we will use techniques to resolve the molecular sequence of events in the cilium and how this information is transduced into the cell to cause cyst formation. This will allow identifying new targets for novel concepts to treat ADPKD

Klaus Tschira Boost Fund

Studienstiftung des deutschen Volkes

Funding University of Bonn

Collaborative Research Grant between the University of Bonn and Emory University, USA

Medical Faculty

Translational Development of Camelid Nanobodies Neutralizing SARS-CoV-2

Intramural Funding from the Medical Faculty

Brigitte und Dr. Konstanze Wegener-Stiftung

SFB TRR57