The Manchot Graduate School Molecules of Infection V (MOI-V) offers an innovative, structured training and research program in a both stimulating and interdisciplinary field of medicine and biology. Highly motivated and excellent candidates holding a MSc degree in biology, biochemistry or related subjects are strongly encouraged to apply. The scholarship comprises inter alia a monthly allowance of 1,900 € over a period of 3.5 years as well as a budget for material expenses and financial support for the attendance of national and international conferences and for a temporary stay abroad. Job profile: The research program of the MOI-V Manchot Graduate School focuses on the characterization and functional dissection of selected host-pathogen interactions at the molecular level and the mechanism that control immunological responses to infectious diseases. In doing so, it follows the highly successful approach adopted in the previous funding periods for MOI-I, MOI-II, MOI-III and MOI-IV. Project 17: The role of the purinergic receptor P2X7 for cross-presentation of antigens during poxviral infection (Prof. Dr. Ingo Drexler, Institute for Virology, HHU Düsseldorf) Vaccinia virus (VACV) belongs to the poxvirus family and is a large dsDNA virus that replicates in the cytoplasm of the infected cell. It encodes more than 200 genes, about a quarter of which have immunomodulatory functions. The virus is an acute infectious agent and has been successfully used in the past as a vaccine for the eradication of smallpox (variola). Attenuated VACV strains such as MVA (modified vaccinia virus Ankara) are tested in clinical trials as recombinant vector vaccines against infectious diseases for their safety and immunogenicity. We have shown that cross-presentation plays an essential role for optimal cytotoxic CD8+ T cell (CTL) responses in this infection model. Cross-presentation enables cell-associated antigens from the extracellular milieu, which are normally presented on MHC class II molecules, to also be presented on MHC class I molecules. This process enables a combined and therefore more efficient CD4+ and CD8+ T cell response to various infectious agents. The investigation of the relevance of cross-presentation for the induction of T cell responses in the VACV infection model in the mouse is a central topic of the research group. In previous work we were able to show that the ability to cross-present is not only determined by the type of cell that presents, but also by the infected cell that provides the antigens. These so-called feeder cells licence bystander non-infected cells to take up the antigens and cross-present them. This process requires both, effector molecules of the innate immune system such as type I interferons as well as components of the signalling pathway for apoptosis such as the purinergic receptor P2X ligand-gated ion channel 7 (P2RX7). As a surface receptor, P2RX7 is mainly expressed in endothelial, epithelial and immune cells. It is involved in the regulation of immune responses via cytokine release, inflammatory processes through inflammasome activation and apoptosis through regulation of mitochondrial activity. Studies show that P2RX7 is also localised intracellularly on mitochondrial structures. The absence of functional P2RX7 in infected feeder cells therefore resulted in a greatly reduced number of cross-presenting dendritic cells (DC), which contained significantly fewer virus-specific peptide/MHC-I complexes on the cell surface. The latter also explains the significantly reduced cytokine production (IFNү, TNFα) of virus-specific CD8+ T cells co-cultured with these cross-presenting DC. In this project, the cellular signalling pathways and molecular processes relevant for efficient cross-presentation will be investigated as a function of P2RX7, both in the feeder cell and in the cross-presenting DC. The planned working program includes the investigation of metabolic processes in the feeder cell with relevance...
تاريخ البدء
2024-10-10
Universitätsstr. 1
40225
Universitätsstr., 40225, Düsseldorf, Nordrhein Westfalen, Deutschland
التقديم عبر
Düsseldorf
Die 2017 gegründete Priavoid GmbH mit Sitz in Düsseldorf ist ein pharmazeutisches Unternehmen, das sich auf die Entwicklung innovativer Therapien für Patienten mit schweren neurologischen Erkrankungen konzentriert. Im Rahmen unserer Wachstumsstrategie suchen wir eine(n) motivierte(n) Kollegin(en) zur Verstärkung unseres Arzneimittelentwicklungsteams.
Technische Assistenz Zellkultur & Analytik (m/w/d)
(Vollzeit, Ref. 109)
Unterstützung des Zellkultur- und Analytik-Teams.
Planung und Durchführung von in-vitro, ex-vivo oder zellulären Assays (u.a. zur Prüfung der Toxizität von Arzneimittelkandidaten oder zur Bestimmung des Transports von Substanzen durch zelluläre Barrieren).
Planung, Durchführung und Analyse von Quantifizierungen mittels HPLC und konfokaler Mikroskopie.
Operative Pflege der Zellkultur.
Allgemeines Labormanagement (z.B. Bestellungen von Verbrauchsmaterialien oder Gerätewartungen).
Ausbildung als Laborant oder technischer Assistent Biologie, Chemie oder Medizin (BTA, CTA, MTA) oder ein Bachelor-Abschluss in Biologie, Biochemie, Biotechnologie, Chemie oder einem verwandten Fachgebiet.
Kenntnisse und praktische Erfahrungen entweder in der Kultivierung von Säugetierzellen oder in der quantitativen (Peptid)-Analyse mittels HPLC. Erfahrung in beiden Bereichen ist von Vorteil.
Sicher im Umgang mit MS-Office. Kenntnisse von laborspezifischer Software sind von Vorteil.
Fließend in Deutsch oder Englisch mit Grundkenntnissen in der jeweils anderen Sprache.
Arbeitssicherheit, Gründlichkeit und Zuverlässigkeit ist Ihnen wichtig.
Einen modernen Arbeitsplatz mit spannenden Möglichkeiten in einem dynamischen Startup-Unternehmen.
Ein exzellentes Forschungsumfeld mit sehr gutem kollegialem Zusammenhalt.
Arbeit an modernen und neuen Laborinstrumenten.
Flexibles Zeitmanagement und einen unbefristeten Arbeitsvertrag.
Düsseldorf
The IUF - Leibniz Research Institute for Environmental Medicine investigates the molecular mechanisms through which particles, radiation and environmental chemicals harm human health. The main working areas are environmentally induced aging of the pulmonary system and the skin as well as disturbances of the nervous and immune system. Through development of novel model systems, the IUF contributes to the improvement of risk assessment and the identification of novel strategies for the prevention / therapy of environmentally induced health damage. The core unit model development is offering a position for a
Cell Biologist (f/m/d) (PhD student).
The position is to be filled at IUF as of April 1st, 2025 We are seeking two highly motivated PhD candidates to join our research team for an innovative Leibniz-funded project, EpiDish, which investigates the impact of environmental pollution on human sensory functions, with a specific focus on taste perception and nutrient sensing. This project, titled Modeling Pollution-Induced Effects on Taste and Nutrient Sensing Using Taste Bud and Stomach Organoids, aims to uncover the cellular and molecular mechanisms by which air- and foodborne pollutants may impair taste perception, disrupt nutrient sensing, and influence health outcomes related to appetite regulation and calorie intake.
The project involves cutting-edge research methods, including organoid models derived from human induced pluripotent stem cells (iPSCs). By generating 3D structures that mimic tongue and stomach tissues, we will assess how pollutants like traffic-related particulate matter and heavy metals alter taste receptor expression, signaling pathways, and nutrient uptake.
This will be paired with sensory trials and data from the NaKo cohort to explore associations between urban pollution exposure and dietary behaviors in different age groups.
The successful candidates will have the opportunity to work with advanced in-vitro models and exposure systems, integrating cellular biology with epidemiological research to address critical questions in public health. This research has the potential to promote healthier eating, reduce malnutrition, and improve well-being by providing evidence for mitigating the effects of pollution on sensory health. We seek a highly motivated candidate (f/m/d) with a solid background in cell biology. Expertise in standard molecular biology techniques, cell culture and ex-vivo models is critical. Previous work with genome editing is a plus. The candidate is required to have strong skills in English and German. Motivation to work independently and be responsible for the daily management of his/her/their research project in coordination with other members of the group is expected. The candidate will also be actively involved in the training and co-supervision of other group members and students.
ROLE RESPONSIBILITIES
The individual should apply their significant expertise in stem cell biology, cell culture and organoids, molecular biology-based techniques, along with their understanding such as plasmid cloning, gene editing, AAV vector production, electroporation, qPCR, RT-PCR, nucleic acid extraction and cloning, gel electrophoresis, macromolecule blotting and probing and mouse handling is highly desirable.
Participate in the development and qualification of assays. Independently analyze data and provide conclusions. Critically evaluate own and others results and offer insights based on process and product understanding to help solve problems.
Contribute to patents, regulatory documents or manuscript as required.
Read scientific and technical literature in order to bring new and improved procedures to the laboratory, and to broaden understanding of disciplines outside area of training. Utilizes all appropriate experimental design methods needed for work in area of specialization. Conduct literature searches and apply knowledge to the approaches taken.
Participate in scientific discuss...
Düsseldorf
The Heinrich-Heine University hosts more than 35,000 students in the beautiful city of Duesseldorf. You will be located at the Department of Neurology, Medical Faculty and University Clinic Duesseldorf. The research training group (RTG) 2578 "Impact of genotoxins on the differentiation efficacy of murine and human stem and progenitor cells and functional competence of thereof derived differentiated progeny" combines groups from the faculties of natural sciences and medicine (https://www.grk2578.hhu.de/en). The research group \"thiology\" is interested in the identification of thiol redox switches regulating physiological and pathological processes. For more information about our research and our activities please see www.thiology.de.
In the project embedded in the RTG2578 (/project 1b) you will investigate the role of hydrogen peroxide in the nucleus. You will discover the impact of this reactive oxygen species on DNA damage and repair, oxidation of proteins and lipids in the nucleus and how these modifcations affect differentiation of neural stem/progenitor cells.
You will plan and perform experiments using in vivo (mice, zebrafish), ex vivo (organotypic slice cultures), and in vitro (cell lines) models and different techniques in the fields of cell biology, biochemistry, and molecular biology.
The results you will present in the RTG seminars on a regular basis, receive feedback and suggestions for further steps in the project and promote the scientific exchange between the projects as well as at international congresses. You are welcome to apply for the position when
- you have a master degree in biology, biochemistry, or related fields
- you have experience with the model organism mouse, cell culture work, and wet lab techniques
- you are motivated to work on a scientific project (which includes sometimes weekends and evenings)
- you are able to use the english language
- you are a teamplayer Your salary will be according to TVL-E13 65% for three years.
In addition to the daily practical laboratory work, the PhD students participate in a extensive training program. This includes lectures about the basics of the RTG topics by the GRK project leaders and invited national and international guest speakers.
Special importance is attached to the further training of the students in areas of modern and future-oriented toxicology, in that they take part in the further qualifying training of the doctoral students to become European Registered Toxicologist.
Furthermore, the students of the RTG 2578 are members of the Interdisciplinary Graduate and Research Academy Düsseldorf (iGRAD) and, depending on their interests, attend workshops and advanced training courses to acquire further key qualifications.
Our research group is part of the neurology research laboratory and offers several national and international collaborations.
Düsseldorf
The Manchot Graduate School Molecules of Infection V (MOI-V) offers an innovative, structured training and research program in a both stimulating and interdisciplinary field of medicine and biology. Highly motivated and excellent candidates holding a MSc degree in biology, biochemistry or related subjects are strongly encouraged to apply.
The scholarship comprises inter alia a monthly allowance of 1,900 € over a period of 3.5 years as well as a budget for material expenses and financial support for the attendance of national and international conferences and for a temporary stay abroad. Job profile:
The research program of the MOI-V Manchot Graduate School focuses on the characterization and functional dissection of selected host-pathogen interactions at the molecular level and the mechanism that control immunological responses to infectious diseases. In doing so, it follows the highly successful approach adopted in the previous funding periods for MOI-I, MOI-II, MOI-III and MOI-IV. Project 17:
The role of the purinergic receptor P2X7 for cross-presentation of antigens during poxviral infection (Prof. Dr. Ingo Drexler, Institute for Virology, HHU Düsseldorf)
Vaccinia virus (VACV) belongs to the poxvirus family and is a large dsDNA virus that replicates in the cytoplasm of the infected cell. It encodes more than 200 genes, about a quarter of which have immunomodulatory functions. The virus is an acute infectious agent and has been successfully used in the past as a vaccine for the eradication of smallpox (variola). Attenuated VACV strains such as MVA (modified vaccinia virus Ankara) are tested in clinical trials as recombinant vector vaccines against infectious diseases for their safety and immunogenicity. We have shown that cross-presentation plays an essential role for optimal cytotoxic CD8+ T cell (CTL) responses in this infection model. Cross-presentation enables cell-associated antigens from the extracellular milieu, which are normally presented on MHC class II molecules, to also be presented on MHC class I molecules. This process enables a combined and therefore more efficient CD4+ and CD8+ T cell response to various infectious agents. The investigation of the relevance of cross-presentation for the induction of T cell responses in the VACV infection model in the mouse is a central topic of the research group. In previous work we were able to show that the ability to cross-present is not only determined by the type of cell that presents, but also by the infected cell that provides the antigens. These so-called feeder cells licence bystander non-infected cells to take up the antigens and cross-present them. This process requires both, effector molecules of the innate immune system such as type I interferons as well as components of the signalling pathway for apoptosis such as the purinergic receptor P2X ligand-gated ion channel 7 (P2RX7).
As a surface receptor, P2RX7 is mainly expressed in endothelial, epithelial and immune cells. It is involved in the regulation of immune responses via cytokine release, inflammatory processes through inflammasome activation and apoptosis through regulation of mitochondrial activity. Studies show that P2RX7 is also localised intracellularly on mitochondrial structures. The absence of functional P2RX7 in infected feeder cells therefore resulted in a greatly reduced number of cross-presenting dendritic cells (DC), which contained significantly fewer virus-specific peptide/MHC-I complexes on the cell surface. The latter also explains the significantly reduced cytokine production (IFNү, TNFα) of virus-specific CD8+ T cells co-cultured with these cross-presenting DC. In this project, the cellular signalling pathways and molecular processes relevant for efficient cross-presentation will be investigated as a function of P2RX7, both in the feeder cell and in the cross-presenting DC.
The planned working program includes the investigation of metabolic processes in the feeder cell with relevance...
Düsseldorf
Das Universitätsklinikum Düsseldorf (UKD) ist das größte Krankenhaus in der Landeshauptstadt und eines der wichtigsten medizinischen Zentren in NRW. Die 9.300 Mitarbeiterinnen und Mitarbeiter in UKD und Tochterfirmen setzen sich dafür ein, dass jährlich über 45.000 Patientinnen und Patienten stationär behandelt und 270.000 ambulant versorgt werden können. Das UKD steht für internationale Spitzenleistungen in Krankenversorgung, Forschung und Lehre, sowie für innovative und sichere Diagnostik, Therapie und Prävention. Patientinnen und Patienten profitieren von der intensiven interdisziplinären Zusammenarbeit der 60 Kliniken und Institute. Die besondere Stärke der Uniklinik ist die enge Verzahnung von Klinik und Forschung zur sicheren Anwendung neuer Methoden. Am UKD entsteht die Medizin von morgen. Jeden Tag.
Für die Klinik für Gefäß- und Endovaskularchirurgie, AG Exp. Vaskuläre Medizin suchen wir ab sofort eine/einen
Medizinische Technologin / Medizinischen Technologen für Laboratoriumsanalytik (MTA-L) (m/w/d)
bzw.
Biologisch-technische Assistentin /
Biologisch-technischen Assistenten (m/w/d)
Herstellung von Lösungen und Zellysaten
Herstellung von histologischen Präparaten
Histologische und immunhistochemische Färbungen
Archivierung von Material- und Gewebeproben
Anzucht und Pflege von Zellkulturen
Verwaltung von Zutrittsberechtigungen
Datensicherung und führen der Probenmateriallisten
Verteilung und Verwaltung der Bestellungen (Bestellliste)
Abgeschlossene Berufsausbildung als MTA-L oder BTA
Erfahrungen in den oben genannten Methoden und Prozessen
Kenntnisse der englischen Sprache erwünscht aber nicht Voraussetzung
Erfahrungen im Umgang mit MS-Office Programmen
Hohe Motivation, Fähigkeit zum selbstständigen Arbeiten
Verantwortungsbewusstsein
Teamfähigkeit
Organisationstalent und Flexibilität
38,5 Wochenarbeitsstunden
Ein qualifiziertes Einarbeitungskonzept
Preiswerte Verpflegungsmöglichkeiten
Innerbetriebliche Fort- und Weiterbildungen
Alle im Öffentlichen Dienst üblichen Leistungen
Kindertagesstätte
Personalunterkünfte
Die Vergütung erfolgt nach TV-L in die Entgeltgruppe 9b unter Anrechnung aller Vorzeiten.
Schwerbehinderte Bewerberinnen/Bewerber werden bei gleicher Eignung bevorzugt berücksichtigt. Teilzeitbeschäftigung ist möglich.
Düsseldorf
Das Universitätsklinikum Düsseldorf (UKD) ist das größte Krankenhaus in der Landeshauptstadt und eines der wichtigsten medizinischen Zentren in NRW. Die 9.300 Mitarbeiterinnen und Mitarbeiter in UKD und Tochterfirmen setzen sich dafür ein, dass jährlich über 45.000 Patientinnen und Patienten stationär behandelt und 270.000 ambulant versorgt werden können. Das UKD steht für internationale Spitzenleistungen in Krankenversorgung, Forschung und Lehre, sowie für innovative und sichere Diagnostik, Therapie und Prävention. Patientinnen und Patienten profitieren von der intensiven interdisziplinären Zusammenarbeit der 60 Kliniken und Institute. Die besondere Stärke der Uniklinik ist die enge Verzahnung von Klinik und Forschung zur sicheren Anwendung neuer Methoden. Am UKD entsteht die Medizin von morgen. Jeden Tag.
Das Institut für Molekulare Medizin II sucht zum nächstmöglichen Zeitpunkt eine/einen
Wissenschaftliche Mitarbeiterin / Wissenschaftlichen Mitarbeiter
(m/w/d) im Bereich Forschungsmanagement
Die Anstellung erfolgt befristet für die Dauer von 2 Jahren. Das Beschäftigungsverhältnis ist gemäß § 14 Abs. 2 des Teilzeit- und Befristungsgesetzs (TzBfG) auf zwei Jahre befristet. Eine Teilzeitbeschäftigung ist möglich.
Administratives Projektmanagement von national und international geförderten Projekten
Projektleitung im Laborbereich (Sicherheitsstufe 2 und tierexperimentelle Arbeiten)
Aufgaben im Bereich der Organisation und Lehre im Studiengang Molekulare Biomedizin
Hilfestellung bei Drittmittelanträgen der Arbeitsgruppenleitung
Unterstützung bei der Organisation und Koordination von Projekten und Meetings der Forschungsprojekte
Verfassen von wissenschaftlichen Projektberichten
Enge Zusammenarbeit mit dem nationalen und internationalen Projektpartner*innen
Abgeschlossenes naturwissenschaftliches Studium, z.B. Biologie, Biochemie, Molekulargenetik o.ä.
Sehr gute englische und deutsche Sprachkenntnisse in Wort und Schrift
Sehr gute mündliche und schriftliche Kommunikations- und Teamfähigkeit
Sehr gutes Organisationsvermögen
Erfahrung im Projektmanagement
Motiviertes und selbständiges Arbeiten
Erfahrung im tierexperimentellen Bereich
Qualifikation und Erfahrung in experimentellen Abläufen (z.B.: Immunologie)
Gewünscht aber nicht Bedingung: Erfahrung im Bereich der Projektleitung
Der Arbeitsvertrag wird mit der Heinrich-Heine-Universität Düsseldorf geschlossen.
Die Vergütung erfolgt nach TV-L in die Entgeltgruppe 13 unter Anrechnung aller Vorzeiten.
Die Heinrich-Heine-Universität Düsseldorf strebt eine Erhöhung des Frauenanteils an. Bewerbungen
von Frauen werden bei gleicher Eignung, Befähigung und fachlicher Leistung daher bevorzugt
berücksichtigt, sofern nicht in der Person eines Mitbewerbers liegende Gründe überwiegen. Die
Bewerbung geeigneter Schwerbehinderter und gleichgestellter behinderter Menschen im Sinne des
SGB IX ist erwünscht.
Düsseldorf
Das Universitätsklinikum Düsseldorf (UKD) ist das größte Krankenhaus in der Landeshauptstadt und eines der wichtigsten medizinischen Zentren in NRW. Die 9.300 Mitarbeiterinnen und Mitarbeiter in UKD und Tochterfirmen setzen sich dafür ein, dass jährlich über 45.000 Patientinnen und Patienten stationär behandelt und 270.000 ambulant versorgt werden können. Das UKD steht für internationale Spitzenleistungen in Krankenversorgung, Forschung und Lehre, sowie für innovative und sichere Diagnostik, Therapie und Prävention. Patientinnen und Patienten profitieren von der intensiven interdisziplinären Zusammenarbeit der 60 Kliniken und Institute. Die besondere Stärke der Uniklinik ist die enge Verzahnung von Klinik und Forschung zur sicheren Anwendung neuer Methoden. Am UKD entsteht die Medizin von morgen. Jeden Tag.
Die Klinik für Dermatologie sucht für das Forschungslabor ab sofort eine/einen
Medizinische*n Technolog*in für Laboratoriumsanalytik (m/w/d)
bzw.
Biologisch-technische*n Assistent*in (m/w/d)
Tierexperimentelle Arbeiten
Genotypisierung transgener und knock-out Mäuse
Isolation und Stimulation von Zellen aus Geweben bzw. Blut humanen und tierischen Ursprungs
Unterhaltung und Pflege der Zellkultur von primären Zellen und etablierten Zelllinien, sowie dem Aufbau und Erhalt einer Zelllinienbank
Assistenz/Unterstützung von Doktorand*innen bei in vivo-/in vitro-Experimenten
Molekularbiologische, proteinchemische, zellbiologische und histologische Techniken, wie PCR; qPCR; Isolation und Aufreinigung von RNA und DNA; Proteinextraktion; Western Blot; ELISA; Immunhistologie; Fluoreszenzmikroskopie; und insbesondere Durchflusszytometrie
Bakterienkultivierung
Anlernen und Einarbeiten von medizinischen und naturwissenschaftlichen Doktoranden/Doktorandinnen
Allgemeine/organisatorische Laborarbeiten
Abgeschlossene Ausbildung als MT-L/BTA
Erfahrung im Umgang mit tierexperimentellen Arbeiten erwünscht, FELASA-B - Schein oder Bereitschaft diesen zu erwerben.
Umfangreiche praktische Erfahrungen im Bereich Durchflusszytometrie
Selbständige Planung und Durchführung einzelner experimenteller Projekte
Etablierung neuer Methoden
Genaue und eigenverantwortliche Arbeitsweise
Eigenständige Literatur- und Web-Recherche
Ein hohes Maß an Motivation; Teamfähigkeit; Belastbarkeit; Flexibilität; Zuverlässigkeit; eigenständiges Arbeiten
Gute EDV- und Englisch-Kenntnisse
Wünschenswert:
Vorkenntnisse in den Bereichen Molekularbiologie; Proteinchemie und Histologie
38,5 Wochenarbeitsstunden
Ein qualifiziertes Einarbeitungskonzept
Innerbetriebliche Fort- und Weiterbildungen
Preiswerte Verpflegungsmöglichkeiten
Alle im Öffentlichen Dienst üblichen Leistungen
Kindertagesstätte
Personalunterkünfte
Düsseldorf
The Manchot Graduate School Molecules of Infection V (MOI-V) offers an innovative, structured training and research program in a both stimulating and interdisciplinary field of medicine and biology. Highly motivated and excellent candidates holding a MSc degree in biology, biochemistry or related subjects are strongly encouraged to apply.
The scholarship comprises inter alia a monthly allowance of 1,900 € over a period of 3.5 years as well as a budget for material expenses and financial support for the attendance of national and international conferences and for a temporary stay abroad. Job profile:
The research program of the MOI-V Manchot Graduate School focuses on the characterization and functional dissection of selected host-pathogen interactions at the molecular level and the mechanism that control immunological responses to infectious diseases. In doing so, it follows the highly successful approach adopted in the previous funding periods for MOI-I, MOI-II, MOI-III and MOI-IV. Project 17:
The role of the purinergic receptor P2X7 for cross-presentation of antigens during poxviral infection (Prof. Dr. Ingo Drexler, Institute for Virology, HHU Düsseldorf)
Vaccinia virus (VACV) belongs to the poxvirus family and is a large dsDNA virus that replicates in the cytoplasm of the infected cell. It encodes more than 200 genes, about a quarter of which have immunomodulatory functions. The virus is an acute infectious agent and has been successfully used in the past as a vaccine for the eradication of smallpox (variola). Attenuated VACV strains such as MVA (modified vaccinia virus Ankara) are tested in clinical trials as recombinant vector vaccines against infectious diseases for their safety and immunogenicity. We have shown that cross-presentation plays an essential role for optimal cytotoxic CD8+ T cell (CTL) responses in this infection model. Cross-presentation enables cell-associated antigens from the extracellular milieu, which are normally presented on MHC class II molecules, to also be presented on MHC class I molecules. This process enables a combined and therefore more efficient CD4+ and CD8+ T cell response to various infectious agents. The investigation of the relevance of cross-presentation for the induction of T cell responses in the VACV infection model in the mouse is a central topic of the research group. In previous work we were able to show that the ability to cross-present is not only determined by the type of cell that presents, but also by the infected cell that provides the antigens. These so-called feeder cells licence bystander non-infected cells to take up the antigens and cross-present them. This process requires both, effector molecules of the innate immune system such as type I interferons as well as components of the signalling pathway for apoptosis such as the purinergic receptor P2X ligand-gated ion channel 7 (P2RX7).
As a surface receptor, P2RX7 is mainly expressed in endothelial, epithelial and immune cells. It is involved in the regulation of immune responses via cytokine release, inflammatory processes through inflammasome activation and apoptosis through regulation of mitochondrial activity. Studies show that P2RX7 is also localised intracellularly on mitochondrial structures. The absence of functional P2RX7 in infected feeder cells therefore resulted in a greatly reduced number of cross-presenting dendritic cells (DC), which contained significantly fewer virus-specific peptide/MHC-I complexes on the cell surface. The latter also explains the significantly reduced cytokine production (IFNү, TNFα) of virus-specific CD8+ T cells co-cultured with these cross-presenting DC. In this project, the cellular signalling pathways and molecular processes relevant for efficient cross-presentation will be investigated as a function of P2RX7, both in the feeder cell and in the cross-presenting DC.
The planned working program includes the investigation of metabolic processes in the feeder cell with relevance...