How does metabolism influence cell fate decisions? What is the energetic cost of morphogenesis, and do cells adapt their metabolism to overcome energetic constraints? How robust are developmental processes, such as patterning and morphogenesis, to changes in the nutritional environment?

While recent advances, including our work, have shed light on certain aspects, these key questions remain largely unanswered. This is why our lab strives to gain a deeper understanding of how the nutritional environment and the cellular metabolic state integrate into developmental processes.

Our long-term goal is to contribute to a deeper understanding of the fundamental principles governing embryonic development. We believe that investigating the role of metabolic processes in cell differentiation and tissue morphogenesis is essential for understanding how environmental factors influence development. This knowledge is not only relevant for in vivo embryogenesis but also has the potential to improve in vitro model systems of human development by establishing more informed and optimized culture conditions.

Our aim is to understand how the metabolic state is involved in the complex regulation of developmental processes and to what extent it serves as an instructive cue. While metabolomics approaches can inform about the metabolic state of tissues, we believe that the development of novel tools to visualize and manipulate metabolism will be crucial for uncovering spatiotemporal metabolic dynamics and their functions. We are particularly interested in the mechanisms by which metabolism regulates developmental signalling pathways and chromatin accessibility, thereby influencing cell fate decisions. Additionally, we seek to understand the role of energy metabolism and energetic constraints in tissue morphogenesis. We believe that such knowledge will be the basis for understanding how changing nutritional conditions impact developmental processes and for elucidating the relationship between metabolic and developmental robustness.

Approach

Our lab uses stem cell-based in vitro model systems, offering a unique window into human development while avoiding ethical concerns associated with studying human embryos. In particular, we focus on micropatterned model systems of gastrulation and neural tube closure, which recapitulate key aspects of early development, including cell differentiation, migration, and tissue morphogenesis.

These systems represent a powerful platform, as pluripotent stem cells are highly amenable to genetic engineering. This enables synthetic biology approaches, including the development of sophisticated (opto)genetic tools for spatiotemporal manipulation of metabolism. The accessibility of these in vitro model systems allows for the real-time study of metabolic and signalling dynamics, while controlled conditions make them ideal for investigating the nutritional environment’s impact on cellular metabolism and behaviour.

Robustness is an important biological concept, referring to the persistence of a process to genetic, environmental, or stochastic variation. However, approximately 70% of human conceptions fail to reach birth, with around 30% believed to be lost during gastrulation. This suggests that gastrulation is a critical developmental stage which might be more susceptible to perturbations. Similarly, neural tube closure defects occur in 1–2 per 1,000 pregnancies, highlighting another vulnerable process during early development. The metabolism of the embryo is especially relevant in this context, as it is strongly influenced by environmental factors such as nutrient availability, oxygen levels, and exposure to toxins.

Our lab uses stem cell-based in vitro models of human gastrulation and neural tube formation to study key aspects of patterning and morphogenesis, including cell fate specification, migration, and epithelial sheet deformation. By combining functional experiments in these in vitro model systems with measurements of clinical samples from human pregnancies, we strive to better understand the nutritional environment during early embryonic development, the influence of maternal diet, and its association with congenital defects and metabolic disorders.