Developmental Mechanobiology

The shape of an animal arises in a species-specific, step-wise fashion during embryonic development. During this sequence of events, collectively referred to as ‘embryo morphogenesis’, the embryo constantly remodels its shape. Our lab is interested in the force-generating mechanisms that drive these shape changes… More about the laboratory

Project: A comparative biophysics approach to understand morphogenetic evolution

Teije Middelkoop

Project description

An enormous diversity of body shapes can be found in the animal kingdom. Animals acquire their final shape in a step-wise fashion during embryonic development in a process referred to as ‘morphogenesis’. The forces that drive these shape changes are generated by the actomyosin cytoskeleton within embryonic cells. Although much has been learned about the force-generating mechanisms that drive morphogenesis, how these physical mechanisms evolve, such that different body shapes arise, remains elusive. In this project the candidate will study morphogenesis from an evolutionary perspective. Actomyosin-driven early embryo morphogenesis will be studied in related nematode species using time-lapse imaging, followed by quantitative image analysis. Moreover, the candidate will perform mechanical perturbations (laser ablations, micro-rheology) to quantify force-generation in developing embryos. This will result in a highly quantitative biophysical characterization of embryo morphogenesis in species covering more than 100 million years of evolutionary distance. Building on previous work (suggested reading), this quantitative framework will reveal which physical processes are under selective pressure. Together with the evolutionary relationships, this approach will reveal how the physical mechanisms underlying morphogenesis have evolved in response to evolutionary forces, like natural selection and drift.

Candidate profile

The developmental mechanobiology lab is looking for a highly motivated and enthusiastic PhD student with a masters degree in biology (genetics, cell biology, developmental biology, evolutionary biology or biochemistry) or physics (biophysics) having experience in practical lab work. Experience with any of the relevant topics or methodology (C. elegans biology & genetics, biophysics, time-lapse imaging, quantitative image analysis using fiji/matlab/python) will be considered positively but is not an absolute requirement. The willingness to learn new techniques and methodology, and operate outside of the comfort zone is however essential. You will be working with genetically modified nematodes and image them using high-end fluorescence microscopy.

Suggested reading

  • Middelkoop TC, Garcia-Baucells J, Quintero-Cadena P, Pimpale L, Yazdi S, Sternberg P, Gross P, Grill SW: CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left-right symmetry breaking. PNAS 2021, 118(20):e2021814118. [pubmed] [doi]
  • Pimpale LG, Middelkoop TC, Mietke A, Grill SW: Cell lineage-dependent chiral actomyosin flows drive cellular rearrangements in early Caenorhabditis elegans development. Elife 2020, 9:e54930. [pubmed] [doi]
  • Naganathan SR, Middelkoop TC, Fürthauer S, Grill SW: Actomyosin-driven left-right asymmetry: from molecular torques to chiral self organization. Curr Opin Cell Biol 2016, 38:24-30. [pubmed] [doi]

Application: https://www.img.cas.cz/career/phd-programme/application/