Characterization of novel molecular pathways regulating immune cell migration
Dendritic cells (DCs) are professional antigen presenting cells. After antigen uptake in peripheral tissues, they initiate to mature and migrate towards lymphoid tissues to present antigen to T cells. DC migration is important for the induction of immune responses against both normal invaders and tumours. The latter is used in cancer immunotherapy for DC-based therapeutic cancer vaccine. Therefore, a proper understanding of the mechanisms regulating DC migration is of utmost importance for the success of such therapy.
In order to migrate, DCs require coordination of a complex series of cytoskeleton and membrane rearrangements. However, the intracellular mechanisms regulating these reorganizations are still largely unknown
Figure 1: Human monocyte-derived dendritic cells. Green: actin; Red: myosin II; Blue: nuclei.
Previously performed screens have identified novel regulators of actin cytoskeleton organization in antigen presenting cells. The aim of this master project is to characterize the role of these identified proteins during DC maturation.
Both human cell lines and monocyte-derived DCs isolated from human blood will be used. The master student will deplete these cells of the proteins of interest by RNA interference and study the effects on the cytoskeleton, macropinocytosis and cell motility using live imaging techniques and migration/chemotaxis assays.
This project will use techniques in biochemistry, cellular and molecular biology, including:
- recombinant DNA technology
- protein expression and purification
- Western blotting
- cell culture (cell lines and primary cells)
- cell transfection
- RNA interference
- migration and uptake assays
- immunofluorescence and state-of-the-art microscopy techniques, using different microscopes available at the NorMic imaging platform.
- quantitative image analysis using software such as ImageJ, Imaris, etc.
Work place and environment:
The project will be performed at the Department of Biosciences in the group of Cinzia Progida (https://www.mn.uio.no/ibv/english/research/sections/fyscell/groups/cell-dynamics-Progida/) . The daily advisors will be the postdocs Irene Persiconi and Khalisah Zulkefli.
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