Přehled
Supervisor
Martin Gregor
Project description
Metastasis critically depends on the ability of single tumour cells to establish and maintain cytoskeletal polarity in three-dimensional environments and in suspension. Recent studies have identified intrinsic actin- and myosin-rich cortical poles and associated cortical flows in detached tumour cells, which correlate with metastatic potential. However, these processes lack a rigorous quantitative and three-dimensional description.
This PhD project aims to develop computational and image-analysis approaches for quantitative characterization of cytoskeletal organization, polarity, and flow dynamics in single metastasizing cells. The project is exclusively in silico and will focus on the analysis of advanced 3D and 4D microscopy datasets.
The student will establish methods for segmentation, reconstruction, and registration of whole-cell cytoskeletal architectures in three dimensions, enabling formal description of polarity axes and cortical asymmetries. Computational approaches such as optical-flow analysis and vector-field modeling will be applied to quantify actin and myosin flows on curved cellular surfaces, capturing directionality, stability, and fluctuations associated with pole formation.
Finally, image-derived features will be integrated with statistical and machine-learning methods to classify polarity states and identify quantitative signatures predictive of metastatic behavior. The project will deliver transferable analytical tools for studying cytoskeletal dynamics in cancer.
Candidate profile
Master’s degree in physics, bioinformatics, applied mathematics, computer science, or a related quantitative field
Strong interest in cytoskeletal dynamics and cancer biology
Proficiency in Python and MATLAB for image and data analysis
Experience with 3D/4D image processing or quantitative modeling
Experience with optical flow, surface-based analysis, or machine learning is an advantage. The candidate should be motivated, independent, and comfortable working in an interdisciplinary environment.
Suggested reading
Ruprecht V., Wieser S., Callan-Jones A., Smutny M., Morita H., Sako K., Barone V., Ritsch-Marte M., Sixt M., Voituriez R., Heisenberg C.-P.: Cortical contractility triggers a stochastic switch to fast amoeboid cell motility. Cell 2015 160(4):673–685.
Lorentzen A, Becker PF, Kosla J, Saini M, Weidele K, Ronchi P, Klein C, Wolf MJ, Geist F, Seubert B, Ringelhan M, Mihic-Probst D, Esser K, Roblek M, Kuehne F, Bianco G, O’Connor T, Müller Q, Schuck K, Lange S, Hartmann D, Spaich S, Groß O, Utikal J, Haferkamp S, Sprick MR, Damle-Vartak A, Hapfelmeier A, Hüser N, Protzer U, Trumpp A, Saur D, Vartak N, Klein CA, Polzer B, Borsig L, Heikenwalder M: Single cell polarity in liquid phase facilitates tumour metastasis. Nat Commun 2018 9(1): 887.
Heikenwalder M., Lorentzen A.: The role of polarisation of circulating tumour cells in cancer metastasis. Cell Mol Life Sci. 2019 76:3765–3781.
APPLY HERE: https://www.img.cas.cz/phd
