PhD

PhD position in Delft, Koenderink Lab: Physics of Collective Metastasis

[28-01-2021]

Job description

Cancer is the second leading cause of death worldwide. The major cause for mortality is the ability of cancer cells to ignore tissue boundaries, invade surrounding tissues, and disseminate to other organs. This process is referred to as metastasis. It has long been thought that cancer cells metastasize by breaking contacts with neighboring cells and traveling as individuals. However, recent evidence suggests that metastasis actually involves collective cell behavior of cells that travel as clusters. In this project, which is part of a large collaboration between physicists and biologists in Delft, Leiden, Nijmegen, and Eindhoven, we aim to understand the physical mechanisms that underlie collective metastasis.

The aim of this PhD project is to find out experimentally how cancer cell clusters invade tissues, and why clusters are more successful than single cells in invasion and dissemination. Our strategy is to use genetically engineered tumor cells varying in deformability, cell-cell -, and cell-matrix adhesion strength, in combination with reconstituted extracellular matrices integrated with microfluidic devices. We will use quantitative time-lapse confocal microscopy and automated image analysis to concurrently track cells and quantify changes in the overall shape and the internal organization of the cell clusters. Using this approach, we will be able to quantify the dependence of the migration efficiency on cell cluster size and identify the sites where cells apply forces to the extracellular matrix by mapping the spatial structure of the strain fields around migrating cell clusters. Moreover, we will study the interplay of the actin, microtubule and intermediate filament cytoskeleton during migration and test whether this interplay is modified when cells move as clusters. These experiments will provide quantitative benchmarks for the computational and analytical models developed by other groups within the consortium, and will also be compared against in vivo observations.

The research environment: We offer an inspiring, supportive and collegial environment. The Koenderink lab is an experimental biophysics lab focused on the mechanobiology of cells and tissues. Our lab combines concepts and techniques from soft matter physics, biophysics, synthetic biology, protein engineering, and cell biology. The Koenderink lab is embedded in the TU Delft Department of Bionanoscience, which focuses on the fundamental understanding of biological processes from molecule to cell. The department features an inspiring, international environment with access to state-of-the art facilities for nanofabrication, a microscopy facility, molecular/cell biology, biochemistry, and high-performance computing for image processing.

Qualifications: We hire outstanding experimental scientists with a strong affinity for research at the interface of physics and biology. Research experience in fields such as biophysics, soft matter science, single-molecule techniques, optical microscopy, nanoscience, and/or quantitative cell biology is welcomed. We are looking for a candidate with a high level of intellectual creativity and genuine interest in fundamental research, who is keen to work in an international and interdisciplinary team.

Info: contact Gijsje Koenderink, g.h.koenderink[at]tudelft.nl

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