Are you fascinated by embryonic development and excited by the idea of imaging the dynamic activity of developmental signaling pathways in a state-of-the-art 3D in vitro model for early embryogenesis? Then this may be the job for you!
We are looking for a PhD candidate to study how individual pluripotent cells decide their future fate in response to developmental signals using gastruloids as a model system. The position is supported by a recently awarded NWO-ENW-XL consortium grant and will therefore be a highly collaborative effort between the University of Amsterdam, Radboud Universiteit, the Netherlands Cancer Institute and the Hubrecht Institute.
You will be embedded in the Developmental, Stem Cell and Cancer Biology group (led by dr. Renée van Amerongen), which is part of the Swammerdam Institute for Life Sciences
in the Faculty of Science at the University of Amsterdam. Research in our group aims to understand how complex tissues are built and maintained. We study this at multiple different levels - "from man or mouse to molecule" - using a variety of experimental approaches and with a specific focus on WNT and BMP/NODAL signaling. See our website
for more details.What are you going to do?
The early mammalian embryo, or epiblast, is composed of pluripotent cells that can generate all specialized cell types of the body. Local gradients of instructive signaling cues determine which developmental trajectory the different cells will take. At the same time, the epiblast cell population is highly heterogeneous with cell-to-cell variation at the transcriptomic and epigenomic level. The goal of our NWO-XL consortium is to unravel how a system that is composed of intrinsically stochastic cells can show robust and deterministic fate decisions.
Your main focus will be on studying the interplay between BMP, WNT and NODAL signaling using live cell imaging in a 3D model of early embryonic development ("gastruloids"). At the start of your PhD, a part-time technician will provide experimental support with setting up the gastruloid cultures from mouse embryonic stem cells (mESCs). As part of our larger consortium network, you will also get the opportunity to incorporate experimental single-cell -omics approaches and computational modeling in collaboration with PhD students and experts throughout the Netherlands (Amsterdam, Utrecht and Nijmegen).
During your PhD research, you will apply a variety of techniques, including (but not limited to) DNA cloning and testing of reporter constructs for BMP, NODAL and WNT signaling, 2D mESC culture and targeting using CRISPR/Cas9, 3D gastruloid culture, live-cell confocal microscopy, FACS sorting, and manipulation of gastruloids using a combination of classical developmental biology and state-of-the-art (epi)genome perturbation approaches.Tasks and responsibilities
- complete a PhD thesis within the official appointment duration of four years;
- use different molecular and cell biology based experimental approaches to visualize and manipulate individual cell behavior
in 3D gastruloids;
- develop and apply quantitative image analysis pipelines (including cell segmentation and tracking with state-of-the art
deep-learning based methods);
- perform your experiments in a systematic and well controlled manner and keep accurate records by properly documenting
and organizing your work;
You will get the opportunity to
- discuss your work in our lab and consortium meetings, incorporate feedback and give input to others;
- assist in teaching and supervise BSc/MSc students during their research internship;
- participate in the Faculty of Science PhD training programme.
- build a network as part of our consortium collaborations;
- present your work at (inter)national meetings in talks or posters;
- continuously hone your academic, professional and personal skills.