ERC Grants und weitere EU-Projekte

ERC Advanced Grants

Die ERC Advanced Grants (bis zu 3,5 Millionen Euro über maximal fünf Jahre) richten sich an etablierte Wissenschaftlerinnen und Wissenschaftler aller Fachbereiche, deren hochinnovative Forschung erheblich über den bisherigen Forschungsstand hinausgeht und neue Forschungsgebiete erschließt.

Folgende Projekte von Mitgliedern der Fakultät werden aktuell im Rhamen eines ERC Advanced Grants gefördert:

ERC Advanced Grant: APROSUS - Microbiome-derived asthma and allergy protective substances for prevention
Projektleiterin: Prof. Dr. Dr. Erika von Mutius
Einrichtung: Kinderklinik und Kinderpoliklinik im Dr. von Hauner'schen Kinderspital
Förderung: 2023 bis 2027

Webseite: Projektbeschreibung in CORDIS
Themen: Asthma affects both children and adults. However, it is the most common chronic disease among children. It is estimated that one in 10 school-age children suffer from asthma. Allergies are also very prevalent, with up to 50 % of children being diagnosed with them. Unfortunately, there is no cure or effective prevention available. The ERC-funded APROSUS project will advance the field of microbiome research towards in-depth characterisation of microbe-derived metabolite complexes to better understand their associated asthma and allergy protective properties. Project work will be based on previous studies carried out by the team, whereby both asthma and allergies were explored together, identifying relevant taxa of the environmental microbiome and discovering microbiome-derived functional agents conferring protection.

Quelle: CORDIS

ERC Advanced Grant: NeuroCentro - Novel mechanisms of neurogenesis- from centrosome to engineering migration
Projektleiterin: Prof. Dr. Magdalena Götz
Einrichtung: Lehrstuhl für Physiologische Genomik, Biomedizinisches Centrum (BMC)
Förderung: 2020 bis 2025

Webseite: Projektbeschreibung in CORDIS
Themen: The centrosome is an organelle that serves as the microtubule-organising centre of the animal cell and is involved in functions such as cell division, cilia formation and migration. Mutations in centrosome-associated proteins lead to brain diseases, but the mechanisms of this process are not known. The EU-funded NeuroCentro project will study fundamental functions of neural-specific centrosome proteins, aiming to understand the brain-specific phenotype of mutations. The research capitalises on a recent project team discovery of novel centrosome-associated RNA-binding proteins in human neural stem cells with significant and selective associations with periventricular heterotopia (PH), a neuronal migration disorder. In the end, researchers will attempt to apply advanced genetic tools to restore centrosome function and revert defects causing PH.

Quelle: CORDIS

ERC Advanced Grant: Immunothrombosis - Cross-talk between platelets and immunity – implications for host homeostasis and defense
Projektleiter: Prof. Dr. Steffen Massberg
Einrichtung: Medizinische Klinik und Poliklinik I
Förderung: 2019 bis 2024

Webseite: Projektbeschreibung in CORDIS
Themen: Pathogen recognition by specific cells of the immune system such as monocytes and neutrophils also activates the coagulation system. This cooperation – known as immunothrombosis – leads to pathogen entrapment, restricting their spread to the vascular compartment and preventing injury of other organs. The scope of the EU-funded IMMUNOTHROMBOSIS project is to dissect the mechanism underlying this phenomenon and understand how it may be implicated in cardiovascular diseases. Researchers will focus on platelets and unveil their role in the homeostatic and pathogenic synergy of thrombosis and inflammation. Results will pave the way towards novel interventions against the formation of thrombi and cardiovascular disease.

Quelle: CORDIS

ERC Consolidator Grants

Die ERC Consolidator Grants (bis zu drei Millionen Euro über maximal fünf Jahre) richten sich an herausragende Nachwuchsforscherinnen und -forscher aller Fachbereiche, deren eigene unabhängige Arbeitsgruppe sich in der Konsolidierungsphase befindet.

Folgende Projekte von Mitgliedern der Fakultät werden aktuell im Rhamen eines ERC Consolidator Grants gefördert:

ERC Consolidator Grant: IMPROVE_LIFE - Investigate maternal and paternal risk factors for violence during pregnancy: lasting impact for everyone
Projektleiterin: Prof. Dr. Heidi Stöckl
Einrichtung: Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE)
Förderung: 2024 bis 2029

Webseite: Projektbeschreibung in CORDIS
Themen: Globally, one in three women are estimated to experience physical and/or sexual intimate partner violence during their lifetime. Pregnancy is a life-changing time, when violence might subside, occur for the first time or intensify. Abuse and its consequences can be severe for both mother and children, and cascade into the next generation.
IMPROVE_LIFE’s aim is to understand the risk and protective factors for violence during pregnancy, its short and long-term effects and intergenerational impact.
This project proposes the first theorization and empirical assessment of violence during pregnancy, its intergenerational transmission, and health and social effects using clinically tested biomarkers. It will synthesize new and existing intergenerational cohort data from diverse settings: Bangladesh and the UK, use pooled multi-country survey datasets and qualitative evidence.
IMPROVE_LIFE will address five objectives: 1) investigate the short- and long-term social and health effects of violence during pregnancy on women and their children, 2) explore if violence during pregnancy is a marker for severe violence, 3) study maternal and paternal risk factors for the transmission of violence to their children, 4) elicit male and female experiences and views of the causes of violence during pregnancy, and 5) provide evidence on the global applicability of established pathways explaining violence during pregnancy.
The fundamental gains for the protection of women and prevention of violence emerging from this ambitious research programme are immense. The high risks arising from following a cohort after two decades, integrating clinically collected biomarkers and male voices are addressed by a dedicated and experienced PI and team and robust research approaches. The new empirically tested, ecological theoretical framework will be vital to inform policy, prevention and response programmes addressing violence during pregnancy, thereby improving lives.

Quelle: CORDIS

ERC Consolidator Grant: CATACLIS - Cancer tailored next generation cellular therapies
Projektleiter: Prof. Dr. Sebastian Kobold
Einrichtung: Abteilung für Klinische Pharmakologie
Förderung: 2024 bis 2029

Webseite: Projektbeschreibung in CORDIS
Themen: "Cellular therapies are commonly used to treat hematological cancers but have yet to be established in solid oncology. Their evolution has been fuelled by hypotheses derived from cell biological observations in cancer models. Most approaches, however, will either never enter clinical development or fail clinical testing, often due to inadequate models of disease and their lack of relevance to human biology.

In CATACLIS, I propose the first unbiased development of cellular products based on patient characteristics in order to address this enormous translational gap and ultimately provide more effective cell therapies to patients with solid cancers. CATACLIS will herald a paradigm shift in cell therapy by reversing conventional model-to-patient innovation (""forward translation"") to patient-generated ideas tested in patient-derived models into clinical trials (""reverse translation"").

I have discovered novel approaches to improve T cell function, which resulted in a clinical trial and established me as a leader in the field of cellular therapies. The challenge I will now face is to move beyond model bias and integrate cancer heterogeneity across patients and entities. In CATACLIS, I will use single cell data sets from patients to inform the design of next generation cellular therapies capable of overcoming current limitations in solid cancers, namely 1) access to tumor tissue, 2) target antigen(s) selection, and 3) immune suppression. To maximize clinical relevance, CATACLIS will use patient-derived materials from hypothesis generation to in vivo testing. This will enable me to create cellular products tailored to the patient´s cancer

My research will not only result in novel cellular products for further testing and development toward clinical trials, but it will also serve as a resource for the development of innovative therapies based on patient data, contribute to the European open science objectives, and reduce the burden of animal experimentation."

Quelle: CORDIS

ERC Consolidator Grant: switchDecoding - Decoding the path to cellular variation within pathogen populations
Projektleiter: Prof. Dr. T. Nicolai Siegel
Einrichtung: Biomedizinisches Centrum (BMC)
Förderung: 2023 bis 2028

Webseite: Projektbeschreibung in CORDIS
Themen: Heterogeneity amongst isogenic cells is pervasive throughout biology. Recently developed single-cell omics approaches are beginning to systematically reveal the repertoire of functionally distinct cell subpopulations within metazoan tissues. Pathogens frequently encounter changing and often hostile environments. To adapt to these challenges unicellular pathogen populations also exhibit a large degree of cell-to-cell heterogeneity, which often affects the outcome of infections. Yet, despite the importance of this cell-to-cell variation, very little is known about the mechanisms that control the level of heterogeneity in pathogen populations or why some isogenic populations are more heterogeneous than others. The goal of switchDecoding is to unveil the path to cellular variation. To this end I will go beyond identifying and describing new subpopulations of cells and elucidate the molecular pathways that establish them and modulate the level of cellular heterogeneity. As a model I will study the mechanism responsible for creating heterogeneity in surface antigen expression in the unicellular parasite Trypanosoma brucei. Antigenic variation is a widely employed strategy by evolutionarily divergent pathogens to evade the host immune response. Using a multidisciplinary approach, I will develop and combine single-cell multi-omics, lineage tracing and CRISPR-Cas-based genome manipulation strategies to characterize the processes, pathways and molecules regulating antigen switching in T. brucei. A better understanding of the mechanisms affecting the level of heterogeneity within a pathogen population will enable us to better predict how pathogens adapt to environmental challenges, including those that lead to the emergence of drug resistance. In the future this knowledge will enable the development of novel intervention strategies: drugs that modulate cell-to-cell heterogeneity to facilitate the clearance of infections.

Quelle: CORDIS

ERC Consolidator Grant: ExoDevo - Extracellular vesicles-mediated cross-talk during human brain development and disease
Projektleiterin: Prof. Dr. Silvia Cappello
Einrichtung: Lehrstuhl für Physiologische Genomik, Biomedizinisches Centrum (BMC)
Förderung: 2022 bis 2027

Webseite: Projektbeschreibung in CORDIS
Themen: Cellular communication is enabled by many factors including secreted vesicles that transfer nucleic acids, lipids, and proteins. Extracellular vesicles (EVs) are involved in neuron-to-neuron communication, while EV's role in the progenitor-to-neuron and -astrocyte communication during brain development has been poorly investigated. Notably, more than 60% of the genes associated with neurodevelopmental diseases encode proteins carried by EVs. The ERC-funded ExoDevo project aims to investigate the role of EVs during brain development. It will focus on the physiological function of EVs, mediating the cell-to-cell signalling, using transcriptomics, proteomics, imaging, and functional analysis of EVs from human cerebral organoids. This study will provide a better understanding of the fundamental mechanisms in brain development and neurodevelopmental pathologies.

Quelle: CORDIS

ERC Consolidator Grant: CALVARIA - Translational aspects of the discovery of skull marrow-meninges connections
Projektleiter: Prof. Dr. Ali Ertürk
Einrichtung: Institut für Schlaganfall- und Demenzforschung (ISD)
Förderung: 2021 bis 2025

Webseite: Projektbeschreibung in CORDIS
Themen: As more and more people around the world are living longer, society is facing growing challenges arising from neurodegenerative diseases affecting millions of people. The recent discovery of the skull-meninges connections (SMCs) that can mediate immune cell trafficking into the brain is extremely promising for new diagnostics and treatments. However, the comprehensive cellular and structural features of the SMCs and the skull/calvaria need further research. The EU-funded CALVARIA project will use advanced experimental technologies of tissue clearing, proteomics and single-cell RNA sequencing to investigate possible exploitation of the discovery for easier access from the skull/calvaria bone marrow, enabling better drug delivery into the brain, control of neuroinflammation and easier detection of brain pathologies.

Quelle: CORDIS

ERC Consolidator Grant: EvoGutHealth - Evolution of gut-associated microbial communities and its functional relevance in health and disease
Projektleiterin: Prof. Dr. Bärbel Stecher
Einrichtung: Max-von-Pettenkofer-Institut
Förderung: 2020 bis 2025

Webseite: Projektbeschreibung in CORDIS
Themen: The highly dynamic gut microbial community plays a fundamental role in human health by facilitating dietary breakdown, production of bioactive metabolites and resistance to infections. The EU-funded project EvoGutHealth aims to understand how the microbe–host relationship may change by the evolution of gut bacteria. Scientists will employ a synthetic community to test the hypothesis that the metabolic interactions between individual bacteria may affect global microbiota functions such as pathogen resistance. The project's results will provide fundamental knowledge on gut microbiota and help develop beneficial intervention strategies that promote human health.

Quelle: CORDIS

ERC Starting Grants

Die ERC Starting Grants (bis zu 2,5 Millionen Euro über maximal fünf Jahre) richten sich an herausragende Nachwuchsforscherinnen und -forscher aller Fachbereiche, die am Anfang einer eigenständigen wissenschaftlichen Karriere in Europa stehen und eine eigene Arbeitsgruppe gründen möchten oder bereits gegründet haben und längerfristig etablieren möchten.

Folgende Projekte von Mitgliedern der Fakultät werden aktuell im Rhamen eines ERC Starting Grants gefördert:

ERC Starting Grant: MEKanics - Cell mechanics of megakaryocytes in 3D tissues - deciphering mechanobiology of platelet formation
Projektleiter: Prof. Dr. Florian Gärtner
Einrichtung: Medizinische Klinik und Poliklinik I
Förderung: 2024 bis 2028

Webseite: Projektbeschreibung in CORDIS
Themen: Homeostatic platelet counts are crucial for vascular integrity and vital to life. Megakaryocytes (MEKs) are giant hematopoietic cells forming large protrusions that fragment to constantly replenish the circulating platelet pool. Nevertheless, severe blood loss, sepsis and aggressive cancer therapies, often cause critically low platelet levels - a major public health problem in Europe's aging population. Despite the unmet clinical need to control platelet production, there is a major lack of knowledge about the mechanistic cell biology of MEKs, hampering the development of innovative therapies. MEKanics will go beyond the state of the art and proposes a combined cell biological and biophysical approach to study MEKs in physiological tissue environments to uncover the mechanical principles that drive platelet formation. I will use quantitative microscopy to characterize cytoskeletal dynamics of MEKs confined in 3D environments of controlled adhesiveness, geometry and stiffness to reveal the mechanisms of force generation and transmission critical for MEK protrusion formation. Further, I will explore how protrusion mechanics affect cytoplasmic transport and partitioning of organelles required for functional platelets. Using super-resolution intravital imaging, I will investigate these processes in their physiological bone marrow niche. By integrating scRNAseq and live-cell microscopy, I will map morpho-dynamics with transcriptomics to identify the gene signature initiating protrusion formation of MEKs in response to mechanical stimuli. A novel MEK cell-system with optimized access to genetic manipulations will allow high-throughput screening of candidate genes. Together, the unique combination of genetics, engineering, quantitative microscopy and intravital tools will provide a holistic cell mechanical model of MEKs in 3D tissues paving the way for new therapeutic approaches to control platelet formation and to advance devices for large-scale platelet production.

ERC StartingGrant: EpiCblood - Towards early cancer detection and tumor classification using epigenomic biomarkers in blood
Projektleiter: Dr. Rodrigo Villaseñor
Einrichtung: Lehrstuhl für Molekularbiologie, Biomedizinisches Centrum (BMC)
Förderung: 2024 bis 2028

Webseite: Projektbeschreibung in CORDIS
Themen: Detecting cancer at an early stage can improve the chances of successful treatment and long-term survival. Dying cells release small DNA fragments wrapped around a core of histone proteins into the bloodstream, called circulating nucleosomes. These carry DNA sequence information and chemical modifications that are stable in the blood, reflecting promising disease biomarkers. The EpiCblood project, funded by the European Research Council, will explore the diagnostic potential of circulating nucleosomes for early cancer detection and tumour classification. The goal is to use several abundant histone modifications and cancer-specific combinatorial histone marks to predict the tissue of origin of the tumour and its gene expression pattern noninvasively. The results may advance liquid biopsy assays for personalised cancer management and early detection.

Quelle: CORDIS

ERC Starting Grant: ImmGenDC - Dissecting the context-specificity of genetic immune regulation in plasmacytoid dendritic cells
Projektleiterin: Dr. Sarah Kim-Hellmuth
Einrichtung: Kinderklinik und Kinderpoliklinik im Dr. von Hauner'schen Kinderspital
Förderung: 2022 bis 2027

Webseite: Projektbeschreibung in CORDIS
Themen: Antiviral immunity and autoimmune diseases exhibit high interindividual variability. Despite intensive research, the genetic and molecular basis of this variability is incompletely understood. A key player of the immune system is the plasmacytoid dendritic cell(pDC). Recent single-cell work revealed functionally distinct pDC subsets. Considering that pDCs respond to many pathogens, this highlights a previously underappreciated functional diversity of pDCs.
I hypothesize that the genetic regulation of pDCs plays a fundamental role in explaining antiviral response and autoimmune variability. Based on my previous work on immune cells, this genetic regulation is expected to be highly context-specific depending on cell type, cell response, ancestry populations and sex among other factors.
The overarching goal of this proposal is to elucidate the context-specificity of immune response and its genetic regulation in pDCs to improve our understanding of human antiviral response variation and pinpoint undiscovered disease pathways of autoimmune diseases.
To this end, I will generate population-scale, linked scATAC-, sc3’RNA- and scLong-read cDNA-seq data of baseline and TLR7-stimulated pDCs from healthy individuals across three ancestry populations. I will identify novel pDC subtypes and their immune-regulatory circuits by integrated multiome analyses. Molecular quantitative trait loci(QTLs) and their degree of context-specificity will be used to build prediction models of genetically determined immune responsiveness and decode autoimmune disease loci to develop mechanistically anchored interventions for precision medicine.
ImmGenDC will gain fundamental insights into the variability of antiviral immune response that will enable the development of new treatments as exemplified by the current pandemic. Importantly, ImmGenDC will also identify genetic determinants of immune variability across diverse ancestry populations thus paving the way for equitable access to medicine.

Quelle: CORDIS

ERC StartingGrant: oxDOPAMINE - Unraveling the mystery of preferential degeneration of midbrain neurons in neurodegerative diseases
Projektleiterin: Prof. Dr. Lena Burbulla
Einrichtung: Lehrstuhl für Stoffwechselbiochemie, Biomedizinisches Centrum (BMC)
Förderung: 2021 bis 2026

Webseite: Projektbeschreibung in CORDIS
Themen: In Parkinson's disease (PD), oxidised dopamine and alpha-synuclein serve as key mediators of mitochondrial and lysosomal dysfunction in midbrain dopaminergic neurons that preferentially degenerate in this progressive movement disorder. The working hypothesis of the EU-funded oxDOPAMINE project is that oxidation of dopamine aberrantly increases in PD. Scientists will investigate pathways of dopamine oxidation that predisposes human neurons to selective vulnerability and degeneration. Based on recent data implicating defective synaptic dopamine metabolism and iron dyshomeostasis in the oxidation of dopamine early in disease pathogenesis, they will study disorders associated with iron accumulation and progressive dopamine neuron degeneration to find common pathogenic mechanisms. Results may lead to novel strategies for restoring synaptic dysfunction and iron homeostasis as a means of preventing neurodegeneration.

Quelle: CORDIS

ERC Starting Grant: T-MEMORE - Thrombotic memory-linking a break in tolerance to platelets to rethrombosis
Projektleiter: Prof. Dr. Konstantin Stark
Einrichtung: Medizinische Klinik und Poliklinik I
Förderung: 2020 bis 2025

Webseite: Projektbeschreibung in CORDIS
Themen: Accumulating evidence indicates that thrombosis - the formation of blood clots - leaves systemic traces and is much more than a local event. The EU-funded T-MEMORE project will test a novel concept that venous thromboembolism is a chronic disease caused by an immune response against activated platelets. Researchers will dissect the mechanisms of platelet production and removal in the bone marrow, spleen and liver and determine the profile of patients at risk or with recurrent thrombotic events. Manipulation of platelet-directed immunity will be tested as an alternative to the standard preventative therapy for venous thromboembolism with anticoagulant.

Quelle: CORDIS

ERC Starting Grant: Neuroprecise - Precision medicine in traumatic brain injury using individual neurosteroid response
Projektleiterin: Prof. Dr. Inga Koerte
Einrichtung: Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Förderung: 2019 bis 2026

Webseite: Projektbeschreibung in CORDIS
Themen: Traumatic brain injury (TBI) affects approximately 1.8 million people in Europe every year. The current patient stratification system is based on the severity of symptoms for diagnosis, prognosis and treatment. However, this does not allow to predict long-term outcomes after TBI. The main hypothesis of the EU-funded NEUROPRECISE project is that TBI leads to a neurosteroid response with individual variability associated with the trajectory of recovery. The project proposes a longitudinal study to characterise neurosteroid response to TBI with respect to age and sex. Researchers will further explore differences in the neurosteroid response for the individually tailored acute therapy and prevention of long-term impairment in a rodent model. NEUROPRECISE strives to overcome barriers in TBI treatment by establishing ways to stratify patients based on the individual differences in the response to TBI.

Quelle: CORDIS

ERC Starting Grant: Proteofit - Adapting protein fate for muscle function and fitness
Projektleiter: Prof. Dr. Alexander Bartelt
Einrichtung: Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten (IPEK)
Förderung: 2019 bis 2025

Webseite: Projektbeschreibung in CORDIS
Themen: Muscle contraction is facilitated by finely orchestrated protein complexes that include actin and myosin. The dynamic maintenance of protein levels (proteostasis) is paramount for muscle tone as well as muscle function in movement and shivering. The EU-funded PROTEOFIT project is interested to understand how muscle senses protein levels and adapts accordingly. Researchers are investigating the molecular mechanisms of muscle adaptation to metabolic changes, hoping to provide key insights into how these mechanisms are perturbed in obesity. Identification of key players in the process is expected to pave the way for novel interventions against obesity and associated disorders.

Quelle: CORDIS

ERC Starting Grant: Baby DCs - Age-dependent regulation of dendritic cell development and function
Projektleiterin: Prof. Dr. Barbara Schraml
Einrichtung: Kinderklinik und Kinderpoliklinik im Dr. von Hauner'schen Kinderspital
Förderung: 2017 bis 2024

Webseite: Projektbeschreibung in CORDIS
Themen: Early life immune balance is essential for survival and establishment of healthy immunity in later life. We aim to define how age-dependent regulation of dendritic cell (DC) development contributes to this crucial immune balance. DCs are versatile controllers of immunity that in neonates are qualitatively distinct from adults. Why such age-dependent differences exist is unclear but newborn DCs are considered underdeveloped and functionally immature.
Using ontogenetic tracing of conventional DC precursors, I have found a previously unappreciated developmental heterogeneity of DCs that is particularly prominent in young mice. Preliminary data indicate that distinct waves of DC poiesis contribute to the functional differences between neonatal and adult DCs. I hypothesize that the neonatal DC compartment is not immature but rather that DC poiesis is developmentally regulated to create essential age-dependent immune balance. Further, I have identified a unique situation in early life to address a fundamental biological question, namely to what extent cellular function is pre-programmed by developmental origin (nature) versus environmental factors (nurture).
In this proposal, we will first use novel models to fate map the origin of the DC compartment with age. We will then define to what extent cellular origin determines age-dependent functions of DCs in immunity. Using innovative comparative gene expression profiling and integrative epigenomic analysis the cell intrinsic mechanisms regulating the age-dependent functions of DCs will be characterized. Because environmental factors in utero and after birth critically influence immune balance, we will finally define the impact of maternal infection and metabolic disease, as well as early microbial encounter on DC poiesis. Characterizing how developmentally regulated DC poiesis shapes the unique features of early life immunity will provide novel insights into immune development that are vital to advance vaccine strategies.

Quelle: CORDIS

Weitere EU-Projekte mit Sprecherschaft

Das europäische Forschungsrahmenprogramm „Horizont Europa“ (2021-2027) bündelt nahezu alle forschungs- und innovationsrelevanten Förderprogramme der Europäischen Kommission.

Aktuell werden folgende EU-Projekte mit Sprechschaft an der Medizinischen Fakultät gefördert:

BMBF/EU-Verbund: UNITE4TB - Academia and industry united innovation and treatment for tuberculosis
Wissenschaftlicher Leiter: Prof. Dr. Michael Hoelscher
Einrichtung: Institut für Infektions- und Tropenmedizin
Förderung: 2021 bis 2028

Webseite: Projektbeschreibung in CORDIS
Themen: Wie bei vielen bakteriellen Erkrankungen gefährdet auch bei der Tuberkulose eine Arzneimittelresistenz die Wirksamkeit der bestehenden Behandlungen. Zwar gibt es bereits neue Medikamente, die klinisch geprüft werden sollen, die Erprobung der verschiedenen Kombinationen bleibt aber doch zeitaufwändig und erfordert gemeinsame Anstrengungen. Das EU-finanzierte Projekt UNITE4TB bringt daher Fachleute auf diesem Gebiet zusammen, um neue Standards für klinische Phase-II-Studien in Bezug auf Tuberkulose zu entwickeln und zu bestimmen. Das Team wird auf bestehende Netzwerke auf allen Kontinenten zurückgreifen, um Patientinnen und Patienten für Studien zu rekrutieren sowie modernste mikrobiologische Methoden und Technologien des maschinellen Lernens einzuführen. Daten zu Biomarkern und zur klinischen Pharmakologie werden den Validierungsprozess der neuen Medikamente begleiten, um ihren späteren Erfolg in der Forschungskette der Wirkstoffentwicklung sicherstellen zu können.

Quelle: CORDIS

ERA-NET: VasOx - Role of oxidative stress for neuro-vascular function
Sprecher: Prof. Dr. Nikolaus Plesnila
Einrichtung: Institut für Schlaganfall- und Demenzforschung (ISD)
Förderung: seit 2022

Webseite: Projektbeschreibung ERA-NET
Themen: Reaktive Sauerstoffspezies (ROS) spielen eine schädliche Rolle bei der Reperfusion nach einer zerebralen Ischämie, der derzeitigen Standardtherapie für ischämische Schlaganfälle. Die genauen vaskulären und zellulären Mechanismen dieser „Reperfusionsschädigung“ sind jedoch noch weitgehend unbekannt, da es an Methoden zur Messung von ROS in vivo und an Tiermodellen fehlt, die eine kontrollierte zeitliche und räumliche Induktion von ROS ermöglichen. In diesem Projekt wird eine neuartige multicistronische chemogenetische Technologie eingesetzt, um ROS zellspezifisch in vivo zu messen und zu induzieren. Diese chemogenetischen Werkzeuge werden in Kombination mit in vivo 2-Photonenmikroskopie und Einzelzelltranskriptomik eingesetzt, um 1) ROS in einem Schlaganfallmodell der Maus in Zellen der neurovaskulären Einheit (NVU) zu messen, um die zelluläre Quelle der ROS-Produktion während der Reperfusion nach zerebraler Ischämie zu identifizieren, 2) die ROS-Produktion in der NVU gesunder Tiere zu induzieren, um die spezifische Rolle von ROS für die neurovaskuläre Funktion und Dysfunktion zu identifizieren, und 3) Gene zu identifizieren, die durch die zellspezifische ROS-Produktion induziert werden. Die Ergebnisse des laufenden Projekts werden das zeitliche und zelluläre Profil der ROS-Produktion nach zerebraler Ischämie aufzeigen und die zugrunde liegende Genexpression entschlüsseln, wodurch neue molekulare und zelluläre Ziele für künftige präzisionsmedizinische Therapeutika für Schlaganfallpatienten definiert werden.

Quelle: neuron-eranet

ERA-NET: BiotaBB - Modulation of brain barrier function by microbiota-derived factors in cerebral ischemia
Sprecherin: Dr. Corinne Benakis
Einrichtung: Institut für Schlaganfall- und Demenzforschung (ISD)
Förderung: seit 2022

Webseite: Projektbeschreibung ERA-NET
Themen: Ziel unseres Projekts „BiotaBrainBarrier“ ist es, die Rolle von aus der Mikrobiota stammenden Faktoren bei der Wiederherstellung der beeinträchtigten Hirnschrankenfunktion bei zerebraler Ischämie zu untersuchen. Jüngste Erkenntnisse zeigen, dass die Darmmikrobiota die Hirnfunktion bei Gesundheit und Krankheit moduliert, indem sie auf die verschiedenen Hirnbarrieren - die Blut-Hirn-Schranke (BHS) und die Hirnhäute - einwirkt. Bisher ist noch nicht untersucht worden, ob Stoffwechselprodukte des Darms die Dysfunktion der Hirnschranken bei Schlaganfall beeinflussen. Hier werden wir das einzigartige und komplementäre Fachwissen von drei Labors kombinieren: Experimentelle Modelle zur Regulierung der Mikrobiota bei zerebraler Ischämie (Benakis, Deutschland), In-vitro-Modelle der menschlichen Darm- und Hirnbarriere (Mustafaoglu, Türkei) und therapeutische Ansätze bei Schlaganfallpatienten (Hirt, Schweiz). Der kombinierte Mehrwert wird es uns ermöglichen, die folgenden Ziele zu erreichen: 1) Testen von mikrobiellen Metaboliten bei der Modulation der Infiltration des Gehirns durch Immunzellen an der meningealen Schranke; 2) Untersuchung der zugrunde liegenden biologischen Mechanismen von mikrobiellen Metaboliten auf die BHS und das Ergebnis des Schlaganfalls; 3) Korrelieren der Ergebnisse aus einer klinischen Sondierungsstudie unter Verwendung eines mikrobiellen Metaboliten. Die Ergebnisse dieses ursprünglichen Vorschlags haben das große Potenzial, neue Erkenntnisse über die Regulierung der Hirnschranke im Zusammenhang mit dem Schlaganfall zu liefern, indem die von der Mikrobiota stammende Komponente kritisch untersucht wird, was ein neues Ziel für die Entwicklung innovativer therapeutischer Strategien für Personen mit zerebrovaskulären Erkrankungen darstellt.

Quelle: neuron-eranet

ERA-NET: IMMOSCAN - The role of immuneosteoclasts in cancer – implications for therapy
Sprecherin: Prof. Dr. Hanna Taipaleenmäki
Einrichtung: Institut für Muskuloskelettale Medizin
Förderung: seit 2022

Webseite
Themen: Primary and secondary bone tumors affect patients from children to elderly. Despite advances in diagnosis and treatment, bone tumors are incurable and thus, new therapies are needed. In the bone microenvironment, cancer cells disrupt the physiological balance between bone forming osteoblasts, bone resorbing osteoclasts and immune cells, leading to excessive osteoclast-mediated bone destruction. Besides standard treatments, including chemo- and radiation therapy and bone-targeted anti-resorptive therapies, immunotherapies have been studied in bone cancers. However, targeting of immune cells largely depends on local microenvironment, which in bone is immunosuppressive, rendering patients with bone tumors less responsive to current immunotherapies.
The goal of the IMMOSCAN consortium is to uncover novel bone cell subpopulations that exert immunomodulatory functions and explore their potential use as novel targets in primary and metastatic bone cancers. Based on our preliminary results and published data we hypothesize that certain bone cells are prone to immune suppression, which might create a permissive microenvironment for cancer and resistance to immunotherapies. During the course of the project, we aim to identify and characterize these cells in the bone-cancer microenvironment and explore mechanisms to target them as a novel therapeutic strategy to improve the efficacy of immunotherapy and control tumor progression in bone. The IMMOSCAN consortium combines complementary and interdisciplinary strengths of five partners that bring together latest imaging and sequencing techniques, cell- and molecular biology approaches, state-of-the-art pre-clinical models as well as patient samples to ensure clinical relevance of the project. The findings of the project are expected to increase our understanding of the complex bone-cancer microenvironment and identify novel targetable pathways for innovative immune therapy in bone cancers.

Quelle: LMU

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