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Our research aims to understand complex cellular dynamics, and particularly the role of physical forces therein. As highly dynamic cells, and with broad importance for animal health, immune cells are of particular interest. At the heart of our research is a biophysical technique I developed during my postdoc. In this approach, deformable microspheres are synthesizedto study the detailed dynamics and forces that play a role in target recognition and killing by immune cells.
Development of new mechanobiology approaches. Although less familiar than genetic or biochemical aspects, physical forces have emerged as key regulators of cellular processes. This includes our immune response, where immune cells use physical forces to guide target selection and enhance target killing. Deformable microspheres are great tools for understanding the role of physical forces in biology because they expand the range of physiological contexts where such measurements can be made. This includes immune cell-target interactions, but also multicellular tissue and even live animals. Multiple technological challenges lie ahead to realize this full potential: more detailed and comprehensive mechanical measurements can be achieved and optimized for use in specific physiological contexts.
Biophysics of phagocytic cup shaping. Phagocytosis, the uptake of large targets by immune cells, is important for clearing bacteria during infection as well as removal of dead tissue cells in homeostasis. Interestingly, this process is mechanosensitive: it is more efficient for stiffer than softer targets. It is currently unknown why this is the case. It is also poorly understood how phagocytes adapt to targets that differ so wildly in size and shape. The cytoskeleton plays a major role in shaping of phagocytic cups and sensing physical target properties. Through fine modulation of target properties, studying cytoskeletal dynamics, and measuring cellular forces, we aim to establish a better understanding of the plasticity of this important immunological process.
Molecular regulation of efferocytosis. A recent focus is on how macrophages clean up dead cells from tissues. They do this by engulfing and subsequently degrading them in a process called efferocytosis. This process is increasingly recognized as a target for therapeutic intervention in the context of atherosclerosis, neurodegenerative disease, and cancer. This form of engulfment is particularly challenging for immune cells, because dying cells are close in their surface chemistry and physical properties to healthy tissue cells. We recently performed a genome-wide CRISPR screen to identify regulators of this process, and are now trying to establish how known and novel regulators, including receptors, precisely function in efferocytosis.
To achieve our goals, we develop biophysical approaches and make use of high-resolution imaging, advanced molecular biology, as well as quantitative data analysis. We are also keen on exploring different (immune) cell-cell interactions. Interested in joining or collaborating? Reach out to daan.vorselen [at] wur.nl