PhD in modeling of cell migration in complex ECMs to decode the risk for young adult skin cancer at Leiden University

The Faculty of Science, the Mathematical Institute and the Institute of Biology are looking for a PhD Student in Theoretical or Mathematical Biology (1.0 FTE)

What you will do

The opening is for a research position within the field of computational science, mathematical or theoretical biology, computational physics, or applied mathematics. This PhD project is part of the EU project PhotoMel (Decoding Early-Life UVA and Skincare Additive Interactions Driving Melanoma Risk and Progression in Young Adults), a multidisciplinary consortium of 7 European universities and partners. Together, PhotoMel aims to prevent melanoma (skin cancer) onset in young adults by decoding the impact of chemical exposures on UVA-induced damage in early childhood, including ECM remodeling and skin cell mutations that shape the melanoma niche.

Your task will be to  further develop two-dimensional models of melanoma cell migration in complex 2D ECMs. The goal will be to determine how UV/chemical-induced ECM changes affect melanoma cell migration, proliferation, and gene expression. We will build upon a recent hybrid Cellular Potts model (hCPM) of cell-ECM interactions, which couples CPMs of cell migration and cell traction with a molecular dynamics model of ECM fiber networks, and a PDE model describing growth factors and ECM-modifying enzymes. Models will be initiated with simulated data and imaging data of skin samples. At a later stage, the models can be extended to three dimensions using software developed concurrently by a postdoc in our team.

The successful applicant will be an integral member of the EU PhotoMel community, which offers an open, diverse and inspiring environment to engage in multidisciplinary cancer research at the intersection of biology, medicine and physics, and is expected to participate in EU PhotoMel events, training and collaborations.

• Develop and interpret novel two-dimensional multiscale mathematical models of cell migration through complex networks of ECM fibers, in close collaboration with members of the PhotoMel consortium.
• Further develop and adapt our two-dimensional simulation techniques to make them suitable for modeling the mechanochemical regulation of melanoma cell migration, in close collaboration with members of the PhotoMel consortium.
• Integrate the new techniques into the Tissue Simulation Toolkit (https://github.com/mathbioleiden/Tissue-Simulation-Toolkit ) and/or other CPM frameworks such as Morpheus or CompuCell3D.
• Design simulation experiments to reflect and interpret ECM modifications due to exposure to UV and skincare additives, based on data obtained elsewhere in the PhotoMel consortium
• Obtain detailed insights into the effects of UV and skincare additives on melanoma progression through simulation experiments guided by literature study, interactions with other participants of PhotoMel consortium and development of advanced distance measures and parameter identification.
• Collaborate with a postdoc working in our group, also within PhotoMel to extend your two-dimensional modeling insights to three dimensions and to validate these against experimental data produced elsewhere in the consortium
• Correct and improve your mathematical models in close collaboration with experimental biologists, including colleagues at the Medical University of Vienna who will image melanoma cell migration and cell-ECM interactions in ex vivo human skin samples and organotypic models
• Publication of the results in the scientific literature and writing a PhD thesis.

What you bring

• Master’s degree in theoretical biology, applied mathematics, computational/theoretical physics, computer science or a related discipline;
• Written and oral proficiency in English, strong scientific writing skills;
• Ability to work independently in a multidisciplinary environment;
• Fluent interdisciplinary communication skills with scientists in cell biology and mathematics;
• Keen interest in cell and developmental biology of cancer;
• Experience in (numerical) mathematical modeling (e.g., Cellular Potts modeling, particle-based simulations, PDEs, FBA);
• Suitable programming skills in C++ or a related language.