PhD

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

[07-05-2020]

PhD: Physics of Collective Metastasis
Genetic programs driving metastasis of solid tumors vary between cancer types, but the ultimate outcome is shared: cancer cells are empowered to pass a series of physical hurdles to escape the original tumor and disseminate to other organs. Accumulating evidence suggests that metastasis involves collective cell behavior whereby cell clusters pass these hurdles more successfully than individual cancer cells. This collective advantage is not understood but in recent years, “active matter” has emerged as a new paradigm to describe collective behavior across length scales. In this project, which is part of a large collaborative program with groups in Delft, Leiden, Nijmegen, and Eindhoven, we will develop and experimentally test a new theoretical framework based on concepts from active matter physics to understand how the collective behavior of cancer cells drives the early stages of metastasis. The Koenderink group will focus on the invasion of cell clusters into the tissues surrounding the tumor, using biomimetic tissue model systems. Cell models engineered by collaborators will be placed in reconstituted ECM networks with controllable stiffness and porosity from key matrix components (collagen, fibronectin, GAGs). Effects of these environmental parameters on cell cluster detachment from tumoroids and subsequent invasion through the ECM will be investigated through quantitative time-lapse confocal microscopy. We will develop automated image analysis to concurrently track cells and quantify changes in overall shape and internal organization of the cell clusters. We can thus quantify the dependence of the migration efficiency of cell clusters on cluster size. We will also integrate the ECM networks in microfluidic devices and microfabricate 1D and 2D confining channels, to assess how cancer cell clusters switch their migration mode to harness topographical guidance cues. Finally, we will develop assays based on digital volume correlation analysis to map the spatial structure of the force fields around migrating cluster. We will thus be able to identify the sites where cells apply forces and correlate these sites with the presence of cell protrusions and the location, size and lifetime of adhesion clusters. Experiments will provide quantitative benchmarks for the computational and analytical models developed by other groups within the consortium, and will be compared against in vivo observations.
Qualifications: I am looking for outstanding experimentalists with a keen interest in research at the interface between physics and biology. Experience in fields such as biophysics, soft matter, single-molecule techniques, optical imaging, nanosciences, and molecular/cellular biology is welcomed.
Applicants must:

    hold a master’s degree, or approach its completion, in physics, chemistry, (bio)engineering (or a closely related discipline)
    have outstanding grades
    have excellent written and spoken English skills
    thrive in a multidisciplinary environment

Please send your resume to: G.H.Koenderink@tudelft.nl

 

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