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Master thesis in Immunology
The laboratory of Immunobiology (PI: Prof. Christoph Hess) at the University Hospital in Basel is looking for a highly motivated student with a background in immunology, cell biology or biochemistry. The project involves characterizing the metabolic signatures of TLR activated human B cells.
Keywords: B cells, TLR, NF-kB, metabolism, immunology, Christoph Hess
B-cells play an essential role in adaptive immunity by providing long-term protection against various microbial infections. Following stimulation of the B cell receptor (BCR) by foreign antigens and cognate interaction with helper T-cells, B cells differentiate into antibody secreting plasma cells (ASC). In recent years, innate immune signals such as PAMPs (pathogen associated molecular patterns) were also found to activate quiescent B-cell populations. The most widely studied of these innate signals are molecules recognized by the Toll-like receptor (TLR) family of pattern recognition receptors (PRR). Exposure to CpG, a TLR9 ligand, results in B cell activation and increased cellular proliferation. This increase in proliferation marks a reprogramming of cellular metabolic pathways. Although numerous studies have delineated the signaling network required for B cell activation and differentiation into ASC following TLR9 stimulation, only few have probed the signaling molecules involved in metabolic remodeling.
NF-kB encompasses a family of transcription factors (RelA, RelB, c-Rel, NF-kB1/p50, NF-kB2/p52) that mediate various biologic processes including immune responses, cell growth, cell adhesion and development. More importantly, NF-kB regulates mitochondrial respiration and aerobic glycosis in various cell types. CpG binding to TLR9 activates the MyD88/IRAK/TRAF6/TAK1 signaling module, which results in a TAK1 dependent activation of the NF-kB pathway. It remains unresolved whether NF-kB impacts metabolic remodeling in CpG stimulated B-cells.
B-cells play an essential role in adaptive immunity by providing long-term protection against various microbial infections. Following stimulation of the B cell receptor (BCR) by foreign antigens and cognate interaction with helper T-cells, B cells differentiate into antibody secreting plasma cells (ASC). In recent years, innate immune signals such as PAMPs (pathogen associated molecular patterns) were also found to activate quiescent B-cell populations. The most widely studied of these innate signals are molecules recognized by the Toll-like receptor (TLR) family of pattern recognition receptors (PRR). Exposure to CpG, a TLR9 ligand, results in B cell activation and increased cellular proliferation. This increase in proliferation marks a reprogramming of cellular metabolic pathways. Although numerous studies have delineated the signaling network required for B cell activation and differentiation into ASC following TLR9 stimulation, only few have probed the signaling molecules involved in metabolic remodeling. NF-kB encompasses a family of transcription factors (RelA, RelB, c-Rel, NF-kB1/p50, NF-kB2/p52) that mediate various biologic processes including immune responses, cell growth, cell adhesion and development. More importantly, NF-kB regulates mitochondrial respiration and aerobic glycosis in various cell types. CpG binding to TLR9 activates the MyD88/IRAK/TRAF6/TAK1 signaling module, which results in a TAK1 dependent activation of the NF-kB pathway. It remains unresolved whether NF-kB impacts metabolic remodeling in CpG stimulated B-cells.
Our laboratory is currently investigating the regulation of metabolic pathways in various lymphocyte populations. For this project, the student will examine the role of NF-kB in regulating CpG mediated metabolic adaptation in B cell subsets. The project will involve the use of tools from molecular and cell biology, biochemistry, metabolism studies and immunology. More specifically, we will utilize immunoblots and immunofluorescence to investigate changes in NF-kB expression and activation following CpG stimulation. We will then probe for alterations in B-cell activation, functionality, and proliferation by using multi-color flow cytometry and ELISA. Additionally, we will utilize quantitative real-time PCR to evaluate alterations in metabolic gene expression and use a metabolic flux analyzer to investigate changes in B-cell metabolic demands. By inhibiting specific components of the NF-kB pathway, we aim to dissect the role of NF-kB in CpG mediated B-cell metabolic remodelling.
Our laboratory is currently investigating the regulation of metabolic pathways in various lymphocyte populations. For this project, the student will examine the role of NF-kB in regulating CpG mediated metabolic adaptation in B cell subsets. The project will involve the use of tools from molecular and cell biology, biochemistry, metabolism studies and immunology. More specifically, we will utilize immunoblots and immunofluorescence to investigate changes in NF-kB expression and activation following CpG stimulation. We will then probe for alterations in B-cell activation, functionality, and proliferation by using multi-color flow cytometry and ELISA. Additionally, we will utilize quantitative real-time PCR to evaluate alterations in metabolic gene expression and use a metabolic flux analyzer to investigate changes in B-cell metabolic demands. By inhibiting specific components of the NF-kB pathway, we aim to dissect the role of NF-kB in CpG mediated B-cell metabolic remodelling.
Please send a motivation letter, CV, relevant documents, and contact details of referees (if possible) via email to - Dr. Glenn R. B. Bantug (glenn.bantug@unibas.ch).
Please send a motivation letter, CV, relevant documents, and contact details of referees (if possible) via email to - Dr. Glenn R. B. Bantug (glenn.bantug@unibas.ch).