Research Article
Julia Wegner, Charlotte Hunkler, Katrin Ciupka, Gunther Hartmann and Martin Schlee (2023) Increased IKKϵ protein stability ensures efficient type I interferon responses in conditions of TBK1 deficiency. Frontiers in Immunology, Volume 14
In this study, Julia Wegner from the working group of Martin Schlee at the Institute of Clinical Chemistry and Clinical Pharmacology at the University Hospital in Bonn and colleagues provide a mechanistic explanation for why TBK1 deficiency is better tolerated than TBK1 mutation in terms of immunocompetence. This study sheds light on the complex regulation of antiviral immune responses and highlights the importance of redundancy in the immune system.
TBK1 and IKKϵ mechanistically explained
TBK1 and IKKϵ are central kinases in the cytosolic nucleic acid sensing pathways that activate type I interferon expression, but the relationship between these two kinases has been unclear. This study by Julia Wegner and colleagues reveals that TBK1 controls the protein expression of its related kinase, IKKϵ, in human myeloid cells. If TBK1 is removed IKKϵ expression is increased and compensate for the loss of TBK1, ensuring unmitigated type I interferon production in conditions of TBK1 deficiency. These findings could lead to the development of interventions to restore an efficient type I IFN response and potentially help to develop new strategies to fight infectious diseases.
Read the full article here.
https://doi.org/10.3389/fimmu.2023.1073608
Keywords: innate immunity, pathogens, virus infection, nucleic acid sensing, cGAS, TBK1, IKKϵ, protein degradation
Job offers at the TRR237
We are currently not offering any positions in our research consortium. Please check back at a later date for updates on future job opportunities.
Other job offers
The research group "Cellular Virology" of Jun.-Prof. Dr. Stephanie Jung at the UKB is currently searching for candidates for a PhD Student position in infection biology (m/f/d).
Here are some key points about the project:
- An interdisciplinary project at the interface of virology, immunology, RNA biology, and extracellular vesicles.
- Explore and discover diverse mechanisms activating/inhibiting and fine-tuning innate immune signaling.
- Use classical methods of the field and self-develop new methods.
Here are some key points about the position:
- 3 years at 65% TV-L E13 with a possibility of extension
- Support for your professional development
- Personal and career development university and non-university courses
For further information, please see the more detailed posting here.
To apply, please contact Prof. Jung ([Email protection active, please enable JavaScript.]) including the reference number 869_2022.
Approved for 2nd Funding Period
The DFG (German Research Foundation) approved our proposal for the second funding period of our TRR237 Nucleic Acid Immunity. Congratulations to all involved, the project leaders, the researchers, and especially our steering committee including our speakers Gunther Hartmann (Bonn), Min Ae Lee-Kirsch (Dresden), and Veit Hornung (Munich).
With our interdisciplinary and highly complementary team of researchers, we look forward to continue asking and answering the pressing questions in the field of Nucleic Acid Immunity.
Doctoral Researcher Symposium 2022
November 10.-12., 2022
Frankfurt am Main
For this year's TRR237 Doctoral Students Symposium, we met for three days in Frankfurt. The focus of this year was to practice defending a doctoral thesis. With presentations of the individual projects as the basis, the students learned general and personal lessons from the meeting and bonded over the exchange of experiences.
Molecular Cell - Volume 82 - Issue 19
On the cover:
In this issue of Molecular Cell, Maharana et al. (pp. 3712–3728) uncovered that the RNase activity of SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA. Within the seemingly unstructured fluid matrix of the cytoplasm (chocolate lentils), biomolecules phase-separate into highly organized structures (yellow and blue clusters) such as stress granules depending on the local concentration of RNA. These condensates sequester immunogenic RNA (red/pink structures), thereby preventing autoinflammation due to aberrant immune recognition of self RNA.
SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA
Authors
Shovamayee Maharana, Stefanie Kretschmer, [...] Thomas Zillinger, [...] Nadja Lucas, Katharina Isabell Maser, [...] Gunther Hartmann, [...] Simon Alberti, and Min Ae Lee-Kirsch
Highlights
- SAMHD1 acts as ssRNA 30exonuclease, the lack of which causes cellular RNA accrual
- Increased ssRNA in cells dissolves RNA-protein condensates, which sequester dsRNA
- dsRNA released from condensates activates type I interferon via innate RNA sensors
- Buffering of immunogenic self RNA by condensates regulates innate immune responses
Nucleic Acid Immunity Meeting 2022
Nucleic Acid Immunity Meeting 2022
September 22-24, 2022
Edinburgh, UK
Organizers: Gunther Hartmann, Yanick Crow, Andrew Jackson
It was a pleasure to co-host the Nucleic Acid Immunity Meeting 2022 together with Yanick Crow and Andrew Jackson from the University of Edinburgh. The meeting program with our fantastic speakers and more information is available on the dedicated meeting's website. Here we want to share some impressions.
Speaker: Carina de Oliveira Mann
The conference included
- 3 Keynote Speakers
- 18 Invited Speakers
- 13 Short Talk Speakers
Location: Edinburgh, UK
The conference was held at the
- Royal College of Physicians of Edinburgh - RCPE
Poster: Daniel Hilbig
The meeting included poster sessions with
- >30 Posters
SAVE THE DATE
35th EMDS Conference
"Myeloid cells in immunoregulatory circuits"
September 19th to 21st, 2022
in Bonn
Organized by
Prof. Zeinab Abdullah, UKB
Prof. Natalio Garbi, UKB
Prof. Elvira Mass, LIMES
Prof. Andreas Schlitzer, LIMES
Advisors
Prof. Christian Kurts, UKB
Prof. Joachim Schultze, LIMES
https://www.macrophage.de/
Tag der Immunologie
Immunintelligenz - Wie clever ist mein Immunsystem?
Feiert den diesjährigen Tag der Immunologie mit uns, und erfahrt wozu euer Immunsystem in der Lage ist!
Wann? Samstag, 30. April, 10:00 - 18:00
Wo? Marktplatz Bonn & Stadtbibliothek Bonn
freier Eintritt
keine Registrierung nötig
Wusstest Du, dass Immunzellen darauf trainiert werden können, Krebs zu bekämpfen? Dass Zellen zwischen ihren eigenen und viralen Nukleinsäuren unterscheiden können? Dass Milch das Immunsystem dazu bringen kann, Nervenzellen anzugreifen? Oder dass Deine Ernährung zu ständigen Entzündungen im Körper führen kann? Beim Tag der Immunologie erfährtst Du mehr darüber, wie Dein Immunsystem funktioniert.
Wissenschaftlerinnen und Wissenschaftler des Exzellenzclusters ImmunoSensation2 und des Transregio 237 werden vor Ort sein, um über ihre aktuelle Forschung zu berichten und Deine Fragen zu beantworten.
Besuch uns am Tag der Immunologie! Wir freuen uns auf Dich!
Samstag, 30. April 2022
Auch in der Stadtbibliothek Bonn sprechen Forscher*innen über Ihre Wissenschaft.
(Haus der Bildung, Mülheimer Platz 1, 53111 Bonn)
10:30 Digitale Therapie von Herzerkrankungen - Der Beginn einer neuen Ära?
Dr. med. Philip Düsing - Herzzentrum Bonn
11:00 Milch: Macht sie kräftig oder krank?
Alicia Weier & Dr. Rittika Chunder - Anatomisches Institut
11:30 Wie man die Bausteine des Immunsystems sichtbar macht - Atom für Atom.
PD. Dr. Gregor Hagelüken - Institut für Strukturbiologie
12:00 Warum macht Fast Food unser Immunsystem krank?
Dr. Anette Christ - Institut für Angeborene Immunität
12:30 Wolf im Schafspelz: Wie kann unser Immunsystem Krebs bekämpfen?
Prof. Dr. Tobias Bald - Institut für experimentelle Onkologie
Ein Voranmeldung zu den Vorträgen ist nicht erforderlich.
Wer die Vorträge online besuchen möchte, kann das hier kostenfrei tun:
https://uni-bonn.zoom.us/j/69552114328?pwd=cCtKMXFNWEZ1anpWNjVkY0tqL1E1UT09
Girls Day 2022
28.04.2022, virtual
Together with the ImmunoSensation2 Cluster and the Aortic Disease Transregio 259, we welcome eight girls from 6th or 7th grade to take a virtual look into a biomedical laboratory. Prof. Dr. Katrin Paeschke will answer questions before we go on a tour of the laboratory itself. The girls will learn how to isolate DNA from fruits and see what they can find with a microbial test kit.
4th-Dresden-Symposium
Unfortunately, we have to postpone the 4th-Dresden-Symposium. Due to the spread of the SARS-CoV-2 variant Omicron, we cannot guarantee a safe meeting at this time.
We will inform you about the new date of the symposium as soon as possible.
Organizers
- Dr. Rayk Behrend
- Prof. Min Ae Lee-Kirsch
- Prof. Claudia Günther
- Prof. Axel Roers
- Prof. Angela Rösen-Wolff
Women Connect Series
Wednesday, October 27th, 2021
On Wednesday, October 27, we start our Women Connect Series, a network for female scientists including workshops, lectures, and networking events. At this first meeting, Eva Lindner introduces strategies and concepts for a compelling media strategy. Participants meet from 9 am to 1 pm in seminar room 8 of the 'Lehrgebäude' at the UKB for the workshop. After the coaching, there will be time for exchange over lunch with other scientists and the coach.
The Women Connect Series is organized by
Marika Enders, Scientific Coordinator TRR259
Alexandra Krämer, Coordinator ImmunoSensation2 Cluster and BIGS
Lucie Delforge, Coordination IRTG2168
Simon Görgen, Scientific Coordinator TRR237
Andrea Rothballer, Scientific Coordinator SFB 1454
Picture A Scientist - Screening & Discussion
The movie "Picture A Scientist" features Biologist Nancy Hopkins, chemist Raychelle Burks, and geologist Jane Willenbring describing their experiences as women in science during their careers. Further, the movie features social scientists, neuroscientists, and psychologists, who provide new perspectives on how to make science itself more diverse, equitable, and open to all.
After screening the movie, we invite you to join our discussion on our experiences and how to address inequalities in our field, moderated by Dr. Cassandra Ellerbe. The discussion is virtual via Zoom. To participate, register for the screening or notify [Email protection active, please enable JavaScript.].
This screening and the discussion is organized by
the Nucleic Acid Immunity Transregio 237,
the Aortic Disease Transregio 259,
the ImmunoSensation2 Excellence Cluster,
and the Bonn & Melbourne Research and Graduate School Immunosciences IRTG2168.
Did you miss the registration? Watch "Picture A Scientist" for 10€ on vimeo.com or register here for the upcoming screening by the University of Bonn.
Career Day
TRR237, TRR259, ImmunoSensation Cluster, IRTG2168, GRK1873
You are currently within your PhD or in your early postdoc and thinking about your next steps?
If the answer is yes and you want to get an overview about your career opportunities:
Take the chance and join the
Career Day – Inside and outside academia
Date: July 01 – July 02, 2021
Time: 9 am – 5pm
Location: online
Some of you may have little insight into potential professional fields.
We would like to broaden your scope and introduce you to the classic paths within and outside of science but also present alternative paths taken by scientists.
The Career Day will help you to clarify a few questions that you may have asked yourself during your scientific education but also expand your expectations: What are the range of potential positions for PhDs? How can you get access in these professional areas? To what extent was and is the PhD helpful? What does every day work look like in different kind of fields?
Inside and outside academia
July 01 – July 02, 2021
We are looking forward to your registration and hope to see you all on our Career Day 2021. Elegible for participation from the side of the TRR237 are all Bachelor, Master, Medical, and PhD Students as well as Postdocs that are members or associated scientists of the Transregio 237. In case you are unsure, contact Simon Görgen as coordinator.
Please register until June 15, 2021:
https://www.umfrageonline.com/s/8712c82
Best Wishes
Marika Enders, scientific coordinator TRR259
Alexandra Krämer, Graduates Program Coordinator (BIGS Immunosciences and Infection) and Gender and Family Support
Lucie Delforge, Coordination Office IRTG2168
Simon Görgen, scientific coordinator TRR237
Tag der Immunologie
24.04.2021 - Online
Für den diesjährigen Tag der Immunologie haben der Bonner Exzellenzcluster ImmunoSensation zusammen mit dem TRR237 Nucleic Acid Immunity und dem TRR259 Aortic Disease ein virtuelles Programm zusammengestellt, um der Öffentlichkeit aktuelle Forschungsthemen vorzustellen. Natürlich stand in diesem Jahr SARS-CoV-2 und wie das Immunsystem auf den Virus reagiert im Focus.
Für die Jüngeren mit Interesse an der Immunologie gab es am frühen Nachmittag ein Live-Experiment, in dem DNA aus Bananen extrahiert wurde. PD Dr. Gregor Hagelüken erklärte das Experiment live Schritt für Schritt und beantwortete die Fragen der Nachwuchsforscher. Nach dem Experiment konnte man zwei Doktorandinnen, M. Sc. Katharina Maus und M. Sc. Nicola Willemsen bei einer Führung durch ein Labor virtuell begleiten und ihnen Fragen zum Labor und ihrem Beruf als Wissenschaftlerinnen stellen.
Abends folgten dann zwei Vorträge und eine Podiumsdiskussion. Im ersten Vortrag stellten Dr. Paul König und Dr. Florian Schmidt von der Core Facility Nanobodies die von ihnen entwickelten kameloiden Antikörper und deren Potenzial in der Behandlung von COVID-19 vor. Im zweiten Vortrag des Abends stellten Dr. Anna Aschenbrenner, Dr. Thomas Ulas und Prof. Dr. Joachim Schultze am Beispiel von SARS-CoV-2 vor, wie mit neuesten Techniken der molekulare Fingerabdruck einer Krankheit entschlüsselt werden kann.
SARS-CoV-2 und das Immunsystem
Den Abschluss des Tages der Immunologie bildete eine Podiumsdiskussion mit Prof. Dr. Gunther Hartmann, Prof. Dr. Eicke Latz und Prof. Dr. Irmgard Förster. Diese Expertengruppe beantwortete zunächst Fragen der Moderatorin Elisabeth Jurack zu Corona und dem Immunsystem, bevor im Hauptteil die Fragen des Publikums beantwortet und diskutiert wurden.
Für das große Interesse möchten wir uns bei den zahlreichen Teilnehmern herzlich bedanken. Ein großer Dank geht auch an all die Forscher die uns diese spannenden Einblicke in ihre Forschung und Arbeit gewährt haben sowie speziell an Elisabeth Jurack, Moderatorin und maßgebliche Organisatorin der Veranstaltung.
Weitere Informationen zum Thema SARS-CoV-2 und das Immunsystem
Wer sich weiterhin informieren möchte, findet auf der Seite der Deutschen Gesellschaft für Immunologie www.das-immunsystem.de unter der Überschrift „Immunologie für Jedermann“ Informationen zu Immunologie allgemein, und zum Tag der Immunologie verschiedene Poster zu Immunologie und SARS-CoV-2. Außerdem findet am Nachmittag des 29.04.2021, dem eigentlichen Tag der Immunologie, eine weitere Vortragsreihe zum Thema Immunologie in Zeiten von COVID-19 statt. Diese wird von Pablo Engel, Clive Gray, Miriam Merad und Federica Sallusto organisiert. Für diese in englisch stattfindende Vortragsreihe mit Podiumsdiskussion kann man sich hier anmelden.
DHX36 Review by Katrin Paeschke and Philipp Schult (A23)
The DEAH helicase DHX36 and its role in G-quadruplex-dependent processes
Abstract
DHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.
Structural basis for sequestration and autoinhibition of cGAS by chromatin
Congratulations to Transregio 237 Researcher Karl-Peter Hopfner (A05), Sebastian Michalski (A05), Carina Mann (A05), Veit Hornung (A09), and colleagues for identifying the 'Structural basis for sequestration and autoinhibition of cGAS by chromatin', published in Nature.
Link to Article
Abstract
cGAS (cyclic GMP–AMP synthase) is an innate immune sensor for cytosolic microbial DNA1. Upon binding DNA, it synthesizes the messenger cGAMP (2’3’ cyclic GMP–AMP)2-4, which triggers cell-autonomous defense and the production of type I interferons and pro-inflammatory cytokines via activation of STING5. Besides responding to cytosolic microbial DNA, cGAS also recognizes mis-localized cytosolic self-DNA and is implicated in autoimmunity and sterile inflammation 6,7.
Sebastian Michalski, Carina C. de Oliveira Mann, Che Stafford, Gregor Witte, Joseph Bartho, Katja Lammens, Veit Hornung, Karl-Peter Hopfner
Specificity towards pathogen or damage associated DNA was thought to be caused by cytosolic confinement. However, recent findings place cGAS robustly in the nucleus8-10, where tight chromatin tethering is even important to prevent autoreactivity to self-DNA8. Here we show how cGAS is sequestered and inhibited by chromatin. We provide a 3.1 Å cryo-electron microscopy structure of the cGAS catalytic domain bound to a nucleosome, which reveals that cGAS does not interact with the nucleosomal DNA, but rather histone 2A/2B, where it is tightly anchored to the “acidic patch”. The interaction buries cGAS’ DNA binding site B, blocking formation of active cGAS dimers. Acidic patch binding robustly outcompetes agonistic DNA, suggesting that nucleosome sequestration can efficiently inhibit cGAS, even when accessible DNA is nearby, such as in actively transcribed genomic regions. Altogether, our work shows how nuclear cGAS is sequestered by chromatin and provides a mechanism for preventing autoreactivity to nuclear self-DNA.
Congratulations to Dr. Christine Wolf for being selected to lead a TRR237 Junior Research Group
July 8th, 2020
Dr. rer. medic. Christine Wolf
Department of Pediatrics
Medical Faculty Carl Gustav Carus
Technische Universität Dresden
Fetscherstraße 74, 01307 Dresden
Molecular and cellular characterization of the nuclease TREX2
We congratulate Dr. Wolf for the selection of her project proposal. The TRR237 'Nucleic Acid Immunity' will fund a Junior Research Group within the collaborative research center at the Medical Faculty of the TU Dresden. Her project will focus on characterizing the functions of the three prime repair exonuclease TREX2 and thereby complement our established projects investigating TREX1 and other nucleases. We wish her good luck and success with her research and are eager to see how her work affects our understanding of Nucleic Acid Immunity.
Follow this LINK for more information on her project.
2019 Retreat of the
On Thursday, November 28th, the Transregio 237 came together to its second retreat. Held in the conference center of the University Innsbruck in Obergurgl, this year's retreat had three main goals. First, the presentation of new data and concepts by project leaders and students. Second, meeting with colleagues to build and strengthen cooperation within the Transregio. And third, discussing the strategic development of projects and the Transregio for the coming years.
Accordingly, the schedule mainly focused on presentations and discussions in the conference hall. A hiking tour through the snowy Alps, fantastic meals, and table tennis matches gave room for discussions in small groups.
Transregio 237
Besides presenting and discussing the scientific developments in Nucleic Acid Immunity, our tight schedule allowed us to enjoy the Austrian Alps as well. A hiking tour along the slopes with the fresh air and some physical activity motivated for the next session. In the evening, after a fantastic dinner, we met for table tennis matches, small group discussions, and a discovery tour of Obergurgl's Nightlife.
Nucleic Acid Immunity
On Sunday, December 1st, we left Obergurgl for this year. Having gained new ideas to be tested within the projects and in cooperation, we are looking forward to our next meeting discussing Nucleic Acid Immunity.
Congratulations to Prof. Gunther Hartmann for being elected as Member of the Henry Kunkel Society.
December 18th, 2019
The Henry Kunkel Society
1230 York Avenue・New York, NY 10065
P: 212-327-7332・F: 212-327-7330
www.henrykunkelsociety.org
[Email protection active, please enable JavaScript.]
The Henry Kunkel Society
The Henry Kunkel Society (HKS) is a prestigious organization dedicated to fostering patient-based and patient-oriented scientific research, particularly in the field of immunology, as exemplified by the scientific life of Dr. Henry Kunkel at Rockefeller University. Originally founded in 1990 and comprising of only 50 members at that time, most of whom were former trainees of Henry Kunkel, the Society has grown to include over 400 elected members, all dedicated to experimental medicine in the field of human immunology. We hope that the Society will continue to grow as an organization that brings together and fosters the success of investigators like Prof. Hartmann, who share this common goal.
CSF Conference
September 22-26, 2019
Monte Verità, Switzerland
Nucleic Acid Immunity
Together with Prof. Andrea Ablasser of the Global Health Institute, EPF Lausanne, Prof. Gunther Hartmann of the SFB/Transregio 237 has hosted the CSF Conference 'Nucleic Acid Immunity in Health and Disease'. The conference was held in Monte Verità, Switzerland, from September 22 to 26, 2019, and featured 20 presentations by outstanding researchers of the field. Amongst the speakers were 6 representatives of our Transregio 237 presenting their projects on nucleic acid immunity. Pictures taken at the conference can be found here.
The UKB Family Room
BMZ Foyer in Bonn, June 26th 2019
The UKB Family Room is supported by the office of gender equality of the UKB, the SFB/Transregio 237, Bo&MeRanG, and the ImmunoSensation2 Cluster.
Picture © Johann Saba / UKB
left to right: Tanja Banavas, Lucie Delforge, Simon Görgen, Alexandra Krämer, Sophie Krimmer
Opening ceremony
The UKB Family Room has officially opened its doors for scientists and coworkers with children. More than 40 interested scientists and colleagues joined the opening ceremony to celebrate and to inform themselves about the possibilities it offers. Ms. Banavas, Ms. Krimmer and Ms. Krämer of the UKB’s gender equality office and ImmunoSensation2 Cluster Coordination Office lead the ceremony and presented the room, located in the biomedical center of the Venusberg Campus. The room is equipped with toys, puzzles, tables, and seats to entertain and comfort children and their parents. For our pregnant colleagues, it provides a daybed for resting phases. Together with PME Family Services, on-location daycare can be provided during conferences and events on the campus. Ms. Kolits, representing PME, further introduced the back-up and emergency service offered for individual daycare in case of a closed KiTa or a sick child.
The support of the UKB Family Room complements our efforts to develop the compatibility for family and working life for our scientists and colleagues.
Poster presentation
‘Vasculitis International Workshop’
April 7-10, 2019
Philadelphia, USA
Nina Kessler (B16) & Susanne Viehmann
Proudly the doctoral students Nina Kessler (right) and Susanne Viehmann (left) present their poster on cGAS/STING in the development of vasculitis. Their poster, presented at the ‘Vasculitis International Workshop’ in Philadelphia, was well received among the participants of the workshop and selected for a poster presentation tour. Nina works on the Transregio project B16 'Cellular and molecular mechanisms of nucleic acid recognition in ANCA-associated pulmonary vasculitis' in the lab of Prof. Garbi at the Institute of Experimental Immunology in Bonn. At the same institute, Susanne conducts her research project in the lab of Prof. Kurts.
We congratulate everybody involved, and especially Nina and Susanne, on their work.
