This year’s Workshop for Experimental Blood and Marrow Transplantation took place in Schweinfurt, a town on the river Main near Würzburg.

From September 19^th to 20^th, 2017 cellular immunotherapy, graft-versus-host disease and inflammation, tumor immunology and immune responses against infections were in the focus of 20 research lectures and seven poster presentations by young scientists from four different universities. This year’s meeting was hosted by the Beilhack lab.  Three other active research groups joined from the Charité Berlin, and the Universities of Frankfurt and Freiburg. The Interdisciplinary Center for Clinical Research (IZKF) Würzburg generously supported this interdisciplinary young investigator meeting. Originally, this workshop had been inspired by the annual Stanford immunology retreats in Asilomar, California, which were always highlights for Robert Zeiser and Andreas Beilhack during their postdoctoral training at Stanford University. After returning to Europe the Zeiser and Beilhack labs initiated an annual two-day scientific workshop together with the young research labs of Evelyn Ullrich and Olaf Penack: Once a year these four research teams meet to discuss recent research progress and new perspectives in the field of hematopoietic cell transplantation and immunotherapy. Beside an intense scientific program there was also time for a brief visit to the Georg Schäfer Museum to enjoy Central European art from the 19^th century. Already we are looking forward to our 10^th workshop, which will be held near Frankfurt am Main in 2018.

A long-standing collaboration with Prof. Edgar Serfling that was initiated in the Transregio SFB TRR52 reseach consortium comes now to fruition. Today, these research findings are being published in the prestigious journal Nature Communications.  

Cytotoxic T lymphocytes are effector CD8⁺ T cells that very efficiently eradicate infected and malignant cells. Our new research publication by Stefan Klein-Hessling and colleagues demonstrates that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activated cytotoxic T lymphocytes, which were deficient for Nfatc1, were also defective to organize their cytoskeleton and to recruit cytosolic organelles to immunological synapses. If CD8⁺ T cells lacked NFATc1, their cytotoxic potential against malignant multiple myeloma cells dramatically declined. Furthermore, mice with NFATc1-deficient T cells could not control Listeria infections.

Extensive transcriptome analysis revealed that NFATc1 controls multiple programs in cytotoxic T cells including the production of cytokines, chemokines and metabolic programs. This new comprehensive study highlights that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions.

Klein-Hessling S, Muhammad K, Pusch T, Klein M, Rudolf R, Flöter J, Qureischi M, Beilhack A, Vaeth M, Kummerow C, Backes C, Schoppmeyer R, Hahn U, Hoth M, Bopp T, Berberich-Siebelt F, Patra A, Avots A, Müller N, Schulze A, Serfling E. (2017). NFATc1 controls the cytotoxicity of CD8+ T cells at multiple levels. Nature Communications 8:511.

Tsetse flies transmit African trypanosomiasis, known as sleeping sickness that causes death months or years after infection. More than 70 million people in sub-Saharan Africa are at risk of this disease.

The cause of these devastating infections are the protozoa of the species Trypanosoma brucei, which is the research focus of the group of Prof. Markus Engstler at the Biocenter at Würzburg University. Thanks to the recently founded DFG graduate college “3D Infect” our research teams connected and studied the week-long journey of Trypanosoma brucei through the different microenvironments of the tsetse fly´s interior organs with advanced microscopy techniques. Dynamic high resolution microscopy revealed the enormous versatility of the incessantly swimming trypanosomes, which cross various barriers and confined surroundings. These rapidly adaptive processes concur with major changes of parasite cell architecture. The new findings by Sarah Schuster et al. about these highly adaptable host-pathogen interactions are now published in the distinguished journal eLIFE.

Schuster S, Krüger T, Subota I, Thusek S, Rotureau B, Beilhack A, Engstler M. (2017). Developmental adaptations of trypanosome motility to the tsetse fly host environments unravel a multifaceted in vivo microswimmer system. Elife. 6: e27656.

This year’s lab retreat took us 20km down the river Main from Frickenhausen to Würzburg City. 

On a stunningly beautiful summer day and removed from the research benches our team reconnected for a canoe tour on the picturesque river Main, embedded between vineyards, old Franconian towns and famous wine villages. We enjoyed the nature of the river, refreshing water and good conversations before finally reaching our destination at Würzburg’s city beach – happy and – for some of us – sore muscles guaranteed.

Today Nature Communications published a new imaging paper on the physiologic regulation of megakaryocytes within the bone marrow microenvironment. 

Hematopoietic stem cells do not only give rise to our body’s immune system but also to megakaryocytes. These giant cells reside in the bone marrow and produce blood platelets required for hemostasis and thrombosis.

In a collaboration project with research groups of the Rudolf Virchow Center and University of Würzburg and Charité Berlin we unravel the spatial organization of megakaryocytes to efficiently sustain the production of blood platelets. Combining different experimental strategies, including light sheet fluorescence microscopy (LSFM), dynamic 2-photon microscopy (2PM) and computer modeling helped to systematically investigate megakaryocyte migration and function within their natural environment.

Our long-standing collaboration partners, Dr. David Stegner and Prof. Katrin Heinze, led this strongly interdisciplinary research project. The new data support a model of spatial megakaryocyte organization to warrant effective platelet production. These novel findings challenge the current thrombopoiesis model of megakaryocyte migration and, instead, support a modified model: Sinusoidal precursors replenish megakaryocytes at sinusoids rather than cells from a distant periostic niche. These findings imply that megakaryocytes, which apparently do not require to migrate in order to reach bone marrow blood vessels, should be just increased by numbers to raise platelet counts in patients.

Reference:

Stegner D, Eeuwijk JMM, Angay O, Gorelashvili M, Pinnecker J, Schmitthausen P, Semeniak D, Friedrich M, Brede C, Beilhack A, Schulze H, Nieswandt B, Heinze KG. (2017). Thrombopoiesis is spatially regulated by the bone marrow vasculature. Nature Communications 8:127.

For two days the DFG research consortium FOR 2314 “Targeting therapeutic windows in essential cellular processes for tumor therapy” met in Würzburg to discuss recent progress in this research endeavor and to expand the collaborative efforts to tackle cancer in new ways.

In 2015 scientists from the Universities of Tübingen and Würzburg joined forces to investigate new strategies for cancer therapy.  The aim of the group is to identify and test new molecular targets for the therapy of solid tumors. Tim Steinfatt presented the Beilhack lab’s recent progress in optical imaging of cancer progression and therapy to address essential processes in pancreatic cancer.

Open PhD position in Immunology & Fungal Research 

A PhD position is available full time to study the interactions between Aspergillus fumigatus and different immune cell population in mouse models of invasive aspergillosis in hematopoietic cell transplantation. 

Thank you for your interest. This position is not available anymore.

Immunology Training Network Erlangen, Tübingen and Würzburg

The Annual Meeting of the immunology graduate programs from three universities convened for the 12^th time

Laudatio for Prof. Thomas Hünig (right), founding father of the graduate college Immunomodulation, by Prof. Hans-Martin-Jäck from Erlangen University

Once a year the PhD students of the graduate program Immunomodulation at Würzburg University are responsible for the independent organization of a Mini-Symposium together with fellow students from Erlangen and Tübingen Universities. This year’s meeting from May 29-31, 2017 took place in the pristine place Kloster Schöntal, one hour South of Würzburg. The Beilhack lab contributed to the scientific program three oral presentations and two scientific posters. Julia Hartweg, Katja Ottmüller and Tim Steinfatt were selected for talks to present and discuss their research progress. Musga Qureischi and Haroon Shaikh presented their research projects at the poster sessions. As a highlight of the meeting, Prof. Hans-Martin Jäck and Prof. Hans-Georg Rammensee honored the manifold scientific achievements of Prof. Thomas Hünig. On top of his stellar scientific career, Prof. Hünig also founded the graduate program Immunomodulation at Würzburg University.

Over the years the annual meeting of the immunology graduate programs has proven highly attractive for scholars, supervisors and guests alike because it can be organized as an exciting, joint undertaking with other graduate colleges working on associated topics. For more than a decade the three-day annual meeting has been organized together with the Graduate Colleges Immunomodulation of Würzburg University, Immunotherapy of Tübigen University and Adaptive Immunity of Erlangen University. The scientific program comprises short presentations of the own work of the scholars in form of oral presentations and a multi-poster session. The preferred venues were solitary conference centres (such as Kloster Banz, Kloster Schöntal or Kloster Neresheim) in beautiful surroundings to encourage the communication between supervisors, guests and the students of the different graduate colleges. Also at this year’s meeting the atmosphere was extremely beneficial for the scholars and the lecturers and enabled close interactions between all participants.

Extension of the DFG CRC/Transregio 124 FungiNet

Continuation of a successful research network until 2021

The Collaborative Research Consortium on pathogenic fungi of the Universities of Jena and Würzburg will continue its joint research endeavor. The German Research Council (DFG) positively re-evaluated the Collaborative Research Centre/Transregio 124 FungiNet. The DFG financially supports its research on fungal infections, which threaten older or immunocompromised patients, e.g. with leukemia or following stem cell or organ transplantation. These infections are hard to manage because of late diagnosis, only limited understanding on the infection mechanisms as well as only few available, partially ineffective, therapeutic measures and increasing drug resistance. Prof. Axel Brakhage, head of this interdisciplinary research consortium, points out that “annually, two million people worldwide contract life-threatening fungal infections. An increasing problem, which causes approximately as many deaths every year as malaria or tuberculosis.”

The Beilhack lab strongly benefits from the interactions within the Collaborative Research Centre/Transregio (CRC/TR) 124 “Pathogenic fungi and their human host: Networks of Interaction” – short “FungiNet” to achieve the ambitious goals to better understand life-threatening fungal infections and to develop new, urgently needed antiinfective therapies.

The FungiNet Research Consortium meeting before the evaluation in February 2017 at the Institute for Molecular Infection Biology (IMIB) on the Medical Campus of Würzburg University

More information about the FungiNet Transregio (CRC/TR) 124 research consortium.

License to subdue

It has long been a puzzle how monocytes can execute entirely opposing immunological programs by either fostering or suppressing inflammation. This puzzle has now been solved in a collaboration project with the group of Prof. Manfred Lutz at the Institute of Immunobiology at Würzburg University. 

Two-step conversion of monocytes into immunosuppressive monocytes

A new publication reveals that the fate and effector functions of differentiating monocytes all depend on the right timing: Early in an immune response, when monocytes encounter activated T cells producing the important cytokines GM-CSF and IFN-γ at inflammatory sites, they differentiate into activated macrophages or dendritic cells and enhance the immune response. However, later in an immune response, monocytes within the bone marrow or spleen are exposed to systemically elevated GM-CSF cytokine levels before they encounter IFN-γ-producing T cells. This means that a two-step licensing process takes place that monocytes can turn into immunosuppressive cells, which are also termed myeloid-derived suppressor cells.

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