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TYK2 and STAT1 as multi-layered regulators in splenic immune and stromal cells


   Department of Biomedical Sciences

   Thursday, September 23, 2021  Funded PhD Project (Students Worldwide)

Vienna Austria Biochemistry Cell Biology Genetics Immunology Molecular Biology Virology

About the Project

Project summary:

Tyrosine kinase 2 (TYK2) was the first member of the family of Janus kinases (JAK1-3, TYK2) for which a biological function in cytokine signalling was demonstrated. Work with gene-targeted Tyk2-deficient mice and human patients with inherited loss- or gain-of-function mutations of TYK2 has led to the elucidation of its contribution to host immunity. Loss-of-function mutations in patients and mice lead to immunological and inflammatory dysfunctions, whereas gain-of-function mutations are associated with or causative for cancers. Our collaborative efforts during the last funding period have shown that TYK2 alters the chromatin activity in immune cells in a highly cell type-specific manner. The TYK2 kinase drives interferon (IFN) signatures in all cell types, albeit to a varying extent. An unexpected feature of TYK2 is that it signals into chromatin in a STAT-independent manner, especially in CD8+ T cells, and profoundly alters the expression of non-IFN target genes annotated to translational processes in homeostatic and activated NK cells and CD8+ T cells. These findings have prompted us to propose complementing the transcriptional data by proteomic analysis in homeostasis and during the immune defence against viral infection. Tissue homeostasis is controlled to a large extent by tonic auto- and paracrine cytokine and growth factor signals. The molecular mechanisms and cellular sources of the tonic signals and responses to them are best studied for the IFN-I system. TYK2 and IFN signalling components are ubiquitously expressed but there have been few investigations of their role in structural cells and tissue/organ homeostasis. We are now planning the first comprehensive analysis of TYK2 and STAT1 functions in splenic stromal cells under homeostasis and during acute inflammation and infection.

The SFB consortium:

The SFB research consortium is coordinated by the University of Veterinary Medicine Vienna and brings together the activities of a network of six laboratories at the Max Perutz Laboratories of the University of Vienna, the Medical University of Vienna and the Research Center of Molecular Medicine (CeMM) of the Austrian Academy of Sciences. Participants benefit significantly from common standards and protocols and from the close collaboration of experts in molecular genetics, epigenetics, tumour genetics, pharmacology, bioinformatics and intensive care medicine, which is unique in the world. This interdisciplinary research in life sciences at the highest level helps excellent PhD students to develop into next generation scientists through a comprehensive research and training program.

Prerequisites

Masters in Cell Biology / Molecular Biology / Life Sciences/Biochemistry / related subjects

A prior hands on experience with routine molecular / cell biology techniques; prior experience with flow cytometry and/or NGS technologies will be a plus

Excellent communication and organizational skills with good knowledge of English language

Willingness to work on small animal models (mice), prior experience will be a plus

Application must include a motivation letter, CV, publication list (if any), transcript of records of the Bachelor's and Master's degree and contact details of two referees. Please send your application to .


Funding Notes

The project is part of a special research program "JAK STAT monarchies" (View Website) funded by the Austrian Science Fund (FWF). The groups aim to gain further insights into the role of the JAK-STAT signalling pathway in the onset, resolution and treatment of infection, inflammation and cancer. The SFB consortium offers a world-class scientific research environment where scientists from different backgrounds interact in an inter-disciplinary, open, and creative environment.

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