Elucidating the role of mechano-signalling feedback in dense cellular collectives
Objectives
Collective tissue behaviour is regulated at multiple length scales, ranging from the molecular to the macroscopic scale. However, virtually all existing models fail to capture this multiscale nature. This project aims to close this gap by developing a coarse-grained multiscale model for cellular collectives. We will explore how subcellular processes such as mechanosensitive signalling underlie the emergence of collective cell jamming and unjamming behaviour [1] – a phenomenon that is crucial in many biological processes such as embryogenesis and cancer metastasis. To model this, we will build upon the celebrated active vertex model [2] and introduce signalling pathways as explicitly dynamic model parameters. In parallel, we will use first-principles active mode-coupling theory [3] to predict and understand how signalling-induced changes affect the collective jamming/unjamming dynamics. The new mechanistic insights derived from the theory predictions can be directly validated in the in-silico vertex model, and also in experiments.
Activities of the Doctoral Candidate
Our combined theory and in-silico multiscale model will allow us to predict the collective dynamics emerging from mechanosensitive coupling, and hence gain new insight into (sub)cellular properties that regulate collective behaviour at the macroscale. In particular, we will elucidate how dynamically changing active stresses and cell shapes, arising from signalling with neighbouring cells, affect the emergent dynamics of the cellular collective. While our focus will be on elucidating the mechanisms that govern collective jamming/unjamming behaviour, the new model may also be applicable to other collective cell phenomena. Experimental validation in vitro is also possible via our established network of experimental collaborators.
Facilities Provided
Access to computing facilities for numerical work, including high performance computing.
Employment Contract
The Doctoral Candidate will be employed on the standard PhD contract at TU/e. The main benefits are:
- Full-time employment for four years. You will spend a minimum of 10% of your four-year employment on teaching tasks, with a maximum of 15% per year of your employment.
- Salary and benefits (such as a pension scheme, paid pregnancy and maternity leave, partially paid parental leave) in accordance with the Collective Labour Agreement for Dutch Universities, scale P (min. € 3,059 - max. € 3,881), further enhanced if the rate stipulated by the EU is higher. Unions negotiate annually for a percentage increase aimed at mitigating inflation.
- A year-end bonus of 8.3% and annual vacation pay of 8%.
- High-quality training programs and other support to grow into a self-aware, autonomous scientific researcher. At TU/e we challenge you to take charge of your own learning process.
- An excellent technical infrastructure, on-campus children's day care and sports facilities.
- An allowance for commuting, working from home and internet costs.
- A Staff Immigration Team and a tax compensation scheme (the 30% facility) for international candidates.
Period of Doctorate and Funding
Doctorates in the Netherlands take 48 months. Since the Doctoral Candidate is formally appointed at Eindhoven University of Technology for the full PhD trajectory, the remaining 12 months of the DC salary will be directly covered by the hiring institution (TU/e).
References
[1] Janssen, LMC. (2019) J. Phys.: Condens. Matter 31, 503002; [2] Sknepnek, R, et al. (2023), eLife 12, e79862; [3] Debets, VE, & Janssen, LMC. (2023) J Chem Phys 159, 014502.