In the University Department of Paediatrics and Adolescent Medicine, there is an immediate vacancy for a
PhD student in Immunology (f/m/d)
in the research group "Molecular Immunology" of PD Marcin Łyszkiewicz, PhD
in the research group "Molecular Immunology" of PD Marcin Łyszkiewicz, PhD
The University Hospital Ulm with its employees (f/m/d) stands for modern patient care with high quality, top research and medical teaching oriented towards the future as well as training in attractive professional fields. The prerequisites for this are qualified and committed employees (f/m/d).
Title: Regulation of T-cell function through changes in local membrane Architecture
About the project: T cells are essential components of the adaptive immune system. Their development and function strictly depend on the quality of the signal transmitted through the T-cell receptor (TCR). The quality of such a signal is not determined only by the receptor structure but also by its cellular context and localisation. Although it is well-established that integrating signal strengths relies on the spatiotemporal organisation of the TCR and associated signalling molecules, the exact molecular mechanisms remain underexplored.
This project will investigate the mechanism of TCR internalisation, in particular, the role of an FCHO1 protein that initiates the process of clathrin-mediated endocytosis. The significance of this protein was revealed in FCHO1-deficient patients who suffer from severe lymphopenia. Using high-end microscopy techniques, including 3D correlative light-electron microscopy (CLEM) and heterologous systems of FCHO1 deficiency exact subcellular localisation of TCR and its partners will be assessed. Here, we will gain information on how internalisation and subcellular localisation of T cell receptors impacts their signalling, gene expression and in consequence activation of corresponding lymphocytes. This will be complemented by studies on murine models of FCHO1 deficiency as well as on primary human material.
Besides 3D CLEM, which will be done in collaboration with the Francis Crick Institute in London, the successful applicant will have the opportunity to experience a wide range of cellular and molecular techniques including advanced flow cytometry, RNA-sequencing and quantitative PCR, immunoprecipitation and mass spectrometry along opportunities to present at scientific conferences and publish the findings.
We offer:
• an exciting disease-oriented research topic
• broad spectrum of methods and state-of-the-art in vitro and in vivo models
• multiple collaborations with excellent national and international research
labs
• work in a young, friendly and highly motivated team
• advanced training opportunities
• salary and benefits according to German TV-L system
About the project: T cells are essential components of the adaptive immune system. Their development and function strictly depend on the quality of the signal transmitted through the T-cell receptor (TCR). The quality of such a signal is not determined only by the receptor structure but also by its cellular context and localisation. Although it is well-established that integrating signal strengths relies on the spatiotemporal organisation of the TCR and associated signalling molecules, the exact molecular mechanisms remain underexplored.
This project will investigate the mechanism of TCR internalisation, in particular, the role of an FCHO1 protein that initiates the process of clathrin-mediated endocytosis. The significance of this protein was revealed in FCHO1-deficient patients who suffer from severe lymphopenia. Using high-end microscopy techniques, including 3D correlative light-electron microscopy (CLEM) and heterologous systems of FCHO1 deficiency exact subcellular localisation of TCR and its partners will be assessed. Here, we will gain information on how internalisation and subcellular localisation of T cell receptors impacts their signalling, gene expression and in consequence activation of corresponding lymphocytes. This will be complemented by studies on murine models of FCHO1 deficiency as well as on primary human material.
Besides 3D CLEM, which will be done in collaboration with the Francis Crick Institute in London, the successful applicant will have the opportunity to experience a wide range of cellular and molecular techniques including advanced flow cytometry, RNA-sequencing and quantitative PCR, immunoprecipitation and mass spectrometry along opportunities to present at scientific conferences and publish the findings.
We offer:
• an exciting disease-oriented research topic
• broad spectrum of methods and state-of-the-art in vitro and in vivo models
• multiple collaborations with excellent national and international research
labs
• work in a young, friendly and highly motivated team
• advanced training opportunities
• salary and benefits according to German TV-L system
Contract: limited
Level of employment: full-time
