"PhD Position Physics of Cellular Robustness"

Join the Laan Lab at TU Delft to unravel the mesoscale physics of how cells maintain robustness through evolution using live-cell imaging and multiscale modelling. Cells are often described as intricate machines where proteins work together in a tightly coordinated fashion to produce essential cellular functions. Yet evolution challenges this picture. Proteins that are crucial for a core function in one species can be completely absent in a close relative—while the function itself remains intact. So, how do cells achieve this robustness when their underlying molecular networks diversify so dramatically over evolutionary time?

Our lab has shown that in budding yeast, the polarity network can adapt to the loss of a key protein by losing three additional proteins. These seemingly destructive changes restore polarity through a collective adaptive response, reshaping many cellular processes at once rather than relying on a few individual proteins. This raises a fundamental question: how do complex cellular networks collectively ensure evolutionary robustness?

Within the ERC project PolarRobustness, you will explore this question as part of a team. Your role will be to investigate the changes in the physical properties of the cell polarity process after the loss of key polarity genes and link it to changes of the spatial–temporal organization of specific polarity proteins through self-organization. Specifically, you will:

• Use high-throughput live-cell microscopy, quantitative image analysis, and set-up super-resolution microscopy to track these changes.
• Combine experimental data with multiscale modelling, in close collaboration with the theoretical physicist Dr. Jos Zwanikken.
• Further develop the mesoscale approach to study cell polarity as a collective physical process: a conceptual framework that is now being developed in the Laan Lab.

You will be part of a multi-disciplinary team, including another PhD student who focusses on the genomics of adaptation and a postdoc who will analyse the evolved strains using mass spectrometry, in collaboration with bioinformatician Dr. Nikolina Sostaric. A dedicated yeast genetics technician will provide strain construction. Together, the team will unravel how molecular changes propagate through the polarity network to collectively enable evolutionary robustness.

The Laan Lab is part of the highly interactive and diverse Department of Bionanoscience at the Faculty of Applied Sciences, TU Delft. To learn more about our work, visit www.tudelft.nl/laanlab.

We are looking for an experimentalist, with a background in (bio)physics, nanobiology or quantitative biology, who is eager to combine wetlab work with modeling and has a keen interest in unraveling cellular resilience. We are a highly collaborative research group that likes to work on challenging and ambitious fundamental problems, that typically combine experiments with computational and conceptual work. We expect the candidate to be a team-player, to have an independent and well-organized work style, to be communicative and creative, and to contribute to our open, interactive, and social lab culture.

Doctoral candidates will be offered a 4-year period of employment in principle, but in the form of 2 employment contracts. An initial 1.5 year contract with an official go/no go progress assessment within 15 months. Followed by an additional contract for the remaining 2.5 years assuming everything goes well and performance requirements are met. Salary and benefits are in accordance with the Collective Labour Agreement for Dutch Universities, increasing from Promovendus gross per month, from the first year to the fourth year based on a fulltime contract (38 hours), plus 8% holiday allowance and an end-of-year bonus of 8.3%.