PhD-student: Constructing active lipid vesicles: a bottom-up synthetic biology approach to studying phagocytosis
As a PhD-student in our Physics of Cellular Interactions group headed by Dr. Kristina Ganzinger, you will apply state-of-the-art techniques to measure the dynamic interplay of a model cytoskeleton and lipid membranes for the first time in the context of phagocytosis. With a lot of room for scientific creativity and collaborations, you will also further extend the capabilities of bottom-up synthetic biology by improving our methods to generate and investigate functionalized giant lipid vesicles (GUVs) using microfabrication techniques.
More about the project
The ability of cells to engulf large objects (phagocytosis) has been conserved from the earliest stages of evolution. Amoeba-like cells use it for food particle uptake, and phagocytes “eat” invading microorganisms or apoptotic cells; a process which is crucial to the innate immune response and tissue remodeling. Despite its profound importance, we still know little about the basic biophysics of phagocytosis. We know that in all instances of phagocytosis, the basic process is always the same: (1) ligand-coated particles bind to receptors, (2) engaged receptors initiate a signaling cascade, (3) the particle is engulfed by actin-driven membrane rearrangement, and (4) upon closure and abscission of the resultant cup, the particle is internalized. Nature has found various ways to orchestrate these four stages on a molecular level. However, these molecular pathways show a high degree of redundancy – so what are the minimal requirements for phagocytosis to occur in its simplest form? And could we recreate a “minimal phagocyte” by building a bio-inspired in vitro model from the bottom up? In order to answer these questions, you will integrate methods from synthetic biology and biochemistry to create functionalized lipid vesicles, and use (single-molecule) fluorescence microscopy to study their properties.
About the group
The group Physics of Cellular Interactions focuses specifically on processes that are critical to the immune system. Inspired by previous research projects that have shown the importance of spatiotemporal constraints for T cell activation (Nat Immun 2016), we investigate the interplay of membrane topography and signaling This means exploring how cells shape their membranes not only in response to signals, but also to detect and discriminate them. We address these questions mainly by reconstituting signaling processes in model-membrane systems (“artificial cells”). By combining this synthetic biology approach with tools from single-molecule biophysics and microfabrication (JACS 2013, PloS One 2013, Nat Comm in press), we can study signaling in isolation from cellular cross-talk.
You are an experimental (bio)chemist or molecular biologist with a strong interest in biophysical questions, or a physicist who has already worked in a wet-lab and is interested in molecular biophysics. Experience with either protein purification, handling lipids or fluorescence microscopy would be an advantage. You should like the idea of working in a collaborative, ambitious and international environment. You will need to meet the requirements for an MSc-degree, to ensure eligibility for a Dutch PhD examination.
Terms of employment
The position is intended as full-time (40 hours / week, 12 months / year) appointment in the service of the Netherlands Foundation of Scientific Research Institutes (NWO-I) for the duration of four years. After successful completion of the PhD research a PhD degree will be granted at one of the universities in the Netherlands. Several courses are offered, specially developed for PhD-students. AMOLF assists any new foreign PhD-student with visa applications and compensates their transport costs and furnishing expense.
Dr. Kristina Ganzinger
Group leader Physics of Cellular Interactions
Phone: +31 (0)20-754 7100
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