The Department of Experimental Biomedicine at the

Rudolf Virchow Center/University Hospital Würzburg invites applications for

6 PhD student positions (f/m/d)

Platelet activation at sites of vascular injury is essential for hemostasis, but in diseased vessels it can also lead to ischemic events, such as heart attack and stroke. Moreover, the interaction of platelets with cells of the immune system (“thrombo-inflammation”) is critically involved in the pathogenesis of inflammatory disease states.

The production of platelets by their bone marrow precursor cells, the megakaryocytes, is tightly controlled and disturbances in this process may result in hemorrhagic disorders and vascular defects.

We focus on transgenic mouse models to study the roles of regulatory proteins (receptors, signaling molecules, cytoskeletal components) for platelet production and function in vitro and in vivo. Our research will yield novel insights into the process of platelet biogenesis and the complex functions of platelets in cardiovascular disease. Our long-term goal is to identify novel targets for the development of improved therapies against vascular diseases.

Activities and responsibilities

We are seeking highly motivated PhD students to work on the following research projects:

We will characterize the functional role of platelet receptor conformation and clustering in signal transduction and the resulting platelet activation and adhesion. The project involves superresolution and expansion microscopy, novel imaging techniques that enable the visualization of single receptors in the platelet membrane. Besides, functional in vitro and in vivo platelet assays on genetic and pharmacological models will be employed.

We will study the mechanisms underlying the physiological role of glycoprotein ectodomains of platelet receptors (GPIb, GPVI, integrins) in hemostasis and thrombosis. The project will particularly employ flow adhesion and flow cytometric assays, as well as in vivo models of arterial thrombus formation. It will furthermore have a strong focus on protein biochemistry and include the use of different heterologous expression systems.

In this project, we will study the diverse functions of platelets and their interaction with immune and cancer cells in inflammatory processes and tumorigenesis. The project will focus on in vivo disease models (platelet metastasis, organ ischemia reperfusion injury) and, besides basic platelet function assays, apply imaging techniques, such as 2-photon, light sheet and confocal immunofluorescence microscopy.

This project will focus on the molecular mechanisms of divalent cation channel signaling in megakaryocytes and its role in platelet biogenesis and function. It involves platelet function assays, such as flow cytometry, aggregometry, flow adhesion studies and biochemistry, as well as different in vivo models of arterial thrombosis. Furthermore, the generation of (pro)platelets by megakaryocytes is studied in vitro using cell culture in combination with imaging techniques, including immunofluorescence confocal and live cell microscopy.

This PhD project will combine murine models of myocardial infarction and ischemic stroke with advanced imaging techniques to dissect the effects of chronic inflammation on megakaryopoiesis. Light sheet fluorescence microscopy and two-photon intravital microscopy will be applied in order to visualize platelet biogenesis and hematopoiesis in chronically inflamed conditions. Besides these key imaging techniques, functional cellular assays as well as biochemical and molecular biology approaches will be part of the PhD project.

This PhD project will combine murine models of hepatic injury with advanced imag-ing techniques to dissect the thrombo-inflammatory pathomechanisms underlying reperfusion injury and the subsequent resolution of inflammation. Light sheet fluo-rescence microscopy and intravital fluorescence (confocal and 2-photon) microscopy will be applied in order to visualize complex cellular interactions between platelets, leukocytes and endothelial cells in the ischemic liver. Besides these key imaging techniques, functional cellular assays as well as biochemical and molecular biology approaches will be part of the PhD project.

Qualification profile

Suitable candidates should hold a Master’s degree or equivalent in a life sciences subject with a strong interest in molecular and (vascular) cell biology/immunology, mouse models and different imaging techniques. Excellent lab skills and good knowledge of the English language are a prerequisite. Previous experience with genetic mouse models and/or in vivo work is highly advantageous.

Benefits

We offer an international and excellent scientific environment that is embedded in the framework of a new German wide research consortium on platelets (www.tr240.de). Its infrastructure is unique in the platelet research field and offers the opportunity to collaborate with national and international basic and translational research groups. The research lab consists of several post-doctoral scientists, PhD students, master students and research assistants.

As a PhD student you will have the opportunity to become part of the international ‘Graduate School of Life Sciences’ (GSLS). The university furthermore offers a comprehensive services concerning administrative and practical matters, e.g. the Welcome Centre (moving to Würzburg) and the International Office.

The salary for this temporary position is commensurate with training and experience according to Collective Agreement for the Public Service of German Federal States TV-L (E13 (65%)). We particularly encourage female scientists to apply. Disabled applicants will be preferentially considered in case of equivalent qualification.

Send applications to

The position will start on March 1st, 2019 or later. Applications should be sent as one single pdf-document including application letter, curriculum vitae, certificates and 2 references by e-mail until February 15th, 2019 to

Prof. Bernhard Nieswandt / Dr. David Stegner (career@platelets.eu)

For further questions please do not hesitate to contact Dr. David Stegner (career@platelets.eu).

Contact

Nieswandt Bernhard
Prof. Dr. rer. nat.
Nieswandt, Bernhard
Coordinator, A01, A07, B07
Bender-Markus
Dr. rer. nat.
Bender, Markus
A04, A06
Stegner David
Dr. rer. nat.
Stegner, David
Scientific Secretary, B06, B08