2 OPEN POSITIONS:
- Dr. Pascal Schneider
- Dr. Gabriela Desdin-Mico
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- Dr. Pascal Schneider
Department of Immunobiology
University of Lausanne, Boveresses 155, 1066 Epalinges, Switzerland
Our research interests:
Our group studies TNF family ligands BAFF, APRIL and EDA (in the context of B cells and plasma cells, humoral immune response, cardiovascular diseases, development of sweat glands and teeth).
Relevant publications:
1. Eslami et al (2024) Unique and redundant roles of mouse BCMA, TACI, BAFF, APRIL and IL-6 in supporting antibody-producing cells in different tissues. PNAS. doi: 10.1073/pnas.2404309121
2. Schneider et al (2023) A causal treatment for X-linked hypohidrotic ectodermal dysplasia: Long-term results of short-term perinatal ectodysplasin A1 replacement. Int. J. Mol. Sci 24:7155. doi: 10.3390/ijms24087155
3. Tsiantoulas et al (2021) APRIL limits atherosclerosis via binding to heparan sulfate proteoglycans. Nature. doi: 10.1038 / s41586-021-03818-3
PhD projects:
Background: The cytokine BAFF is required for the survival and fitness of naïve mature B cells in the periphery. To do so, it engages a specific receptor, BAFF-R, expressed on B cells. APRIL is another cytokine, related to BAFF, that does not bind to BAFFR. However, both BAFF and APRIL engage two further receptors, TACI and BCMA, that are important for antibody-producing plasma cells, and thus for the humoral immune response. APRIL is a very basic (positively charged) protein that also additionally binds to negatively charged proteoglycans. Dysregulations of BAFF, APRIL or their receptors are linked to immunodeficiencies and to autoimmunity. In the genome, the gene of APRIL is preceded by the gene of TWEAK, another ligand related to APRIL. These genes are so close that trans-splicing events can occur, generating a chimeric protein, TWE-PRIL, starting with TWEAK (intracellular and transmembrane domains) and ending in APRIL (receptor-binding domain). APRIL also exists in a form (or in forms) unable to bind to TACI and BCMA, but linked to cardiovascular diseases. In this respect, APRIL can be found bound to proteoglycans in arteries, limiting atherosclerotic plaque formation. Ectodysplasin A (EDA) is structurally related to BAFF and APRIL, but plays a totally different function. It is required for the development of skin appendages including teeth and sweat glands. EDA deficiency causes a genetic disease (an ectodermal dysplasia) that is particularly handicapping, in part because lack of sweat glands severely impairs thermoregulation. Over the years, a project to cure the disease by providing recombinant EDA to EDA-deficient fetuses was developed for mice and humans and reached clinical stages.
Aim of the PhD project: The project will tackle one or more of the following questions: what is the origin of circulating EDA in the blood (using a genetic mouse model)? What is the structure of the collagen domain and of the long protein sequence linking the transmembrane domain to the receptor-binding domain of EDA (using recombinant proteins and electron microscopy)? Can we bring a genetic proof that APRIL is indeed bound to arteries, and if yes can it be modulated with pharmacological agents (knock-in mice, antibodies, immunofluorescence)? What is non-canonical APRIL (i.e. the form of APRIL linked to cardiovascular diseases), how is it formed, what does it do (recombinant proteins, human serum, cell-based assays, electron microscopy)? Does TWE-PRIL participate to immune or artery functions (knock-out mice, plasma cells)?
PhD student profile:
• Interested in protein biochemistry and in the link between protein and function
• Interested to work with genetically modified animal models
• Strong background in immunology and molecular biology
• Curious, eager to make a difference, and goal-oriented
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- Dr. Gabriela Desdin-Mico
PhD Position - SNSF AMBIZIONE Junior Group of Dr. Gabriela Desdin-Mico
start date: January 2025
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