Metabolic Origins: Steering of early developmental fate #MetabolismMondays

All the world’s a metabolic dance, early career scientists are leading the way!

Emerging perspectives in metabolism

This week we’ll meet Dr Kristina Stapornwongkul, a new incoming faculty at IMBA, Vienna where her lab will focus on how metabolism influences the dynamic process of embryonic development. Kristina’s journey into the world of biology began with a simple school experiment involving potatoes, iodine, and saliva—an early lesson in the unseen chemical choreography that drives life. Today, she is at the forefront of a rapidly evolving field that explores how metabolism shapes embryonic development. With a background in developmental biology and a growing toolkit of synthetic and molecular approaches, Kristina investigates how cellular metabolism influences stem cell fate decisions during the earliest stages of life. Her recent work using gastruloids – a stem cell-based model of early embryos, reveals how metabolic pathways like glycolysis do more than supply energy; they act as key regulators of signaling and pattern formation. She often refers to metabolites and metabolic enzymes as “moonlighting” agents, highlighting their unexpected and influential roles in directing cellular behaviour. As she prepares to launch her own lab at IMBA in Vienna, Kristina is driven by a deep curiosity about how cells make decisions under changing nutritional conditions, and how robust development is maintained despite metabolic challenges. Through her interdisciplinary lens, she brings fresh insights into how environmental and cellular metabolism shape the blueprint of life. Check out her Lab page here and give her a follow over Twitter and Bluesky. She will be hiring soon at all levels so please reach out to her if you’re interested !

What was your first introduction to the field of metabolism, what’s your first memory?

It was actually the first experiment I ever did in school: an iodine starch test with potatoes. We took a potato slice and applied saliva to one half before adding the iodine solution, which normally turns black in the presence of starch. The half without saliva turned black as expected, while the other half didn’t—showing that something in the saliva had already broken down the starch into simpler sugars. That clear, visual result was such a striking demonstration of how our bodies are built to break down food, and I think that’s why it made such a lasting impression on me.

Tell us how you got interested in the field of nutritional and metabolic aspects of animal development from a cell cycle/cell fate perspective?

I did my Master thesis in the Aulehla lab which did some pioneering work in the field of developmental metabolism at that time. It was a completely new and fascinating concept for me. So even though I didn’t work on a metabolism-related project myself at that time, it really got me interested in that topic.

Your work intersects metabolism, development and cell biology. How do you integrate these disciplines in your research, and what unique insights have emerged from this approach?

To understand how metabolism shapes development, I believe we need to uncover molecular mechanisms at the cellular level and understand how they influence tissue-level behaviour and function. So far, my work has been mainly based on developmental and synthetic biology approaches. Looking ahead, I would like to incorporate mass spec-based readouts and develop new tools to manipulate metabolism in a targeted manner.

Introduce us to the field of embryonic development and how does cellular metabolism influence stem cell behavior and fate decisions during embryonic development. Tell us about your recent work on the relationship between glucose metabolism and signaling pathways during cell fate determination during embryonic development?

In the last decade, it has become increasingly clear that metabolic pathways do more than meet the bioenergetic needs of cells—they also play an active role in regulating differentiation. The underlying mechanisms include metabolite-driven post-translational modifications, metabolite-protein interactions, and moonlighting functions of metabolic enzymes, which can influence the epigenetic and signalling state of cells. Based on this, I set out to investigate whether the metabolic state can significantly impact cell fate decisions during the exit from pluripotency.

Using an in vitro model for gastrulation based on mouse embryonic stem cells (gastruloids), we found that inhibiting glycolysis promotes ectodermal differentiation at the expense of mesoderm and endoderm lineages. This effect is dose-dependent, indicating that germ layer proportions can be modulated by adjusting exogenous glucose levels. We further showed that glycolysis acts upstream of key developmental signalling pathways, including Nodal and Wnt, and that its influence on cell fate can be separated from its effects on growth. DOI: 10.1016/j.stem.2025.03.011.

What evidence supports the idea that glycolytic activity acts as a signaling regulator rather than merely an energy source during gastruloid development and what are the broader implications of glycolysis functioning as an activator of morphogen signaling pathways in early development?

The inhibition of glycolysis resulted in the clear downregulation of Nodal and Wnt signalling targets, which are absolutely required for mesoderm and endoderm specification. This suggested that glycolytic activity might be upstream of morphogen signalling. To test this we tried to rescue the phenotype by activating Nodal or Wnt signalling while inhibiting glycolysis. To my surprise, this restored normal germ layer patterning, even though glycolytic activity and overall growth were not recovered. That indicates that glycolysis is not merely fueling signalling but rather functions as an upstream activator!

Tell us about gastruloids as a model. In your view, what advantages do gastruloids offer for understanding early development and metabolism?

The original work establishing gastruloids as a model is here – https://doi.org/10.1242/dev.113001. For me, stem cell-based model systems are an exciting and versatile tool for studying specific processes during development. Pluripotent stem cells are easy to genetically engineer, which opens the door to powerful synthetic and (opto)genetic tools for controlling metabolism in space and time. Their accessibility makes it possible to observe metabolic and signalling dynamics in real time, and the controlled culture conditions allow us to explore how different nutritional environments influence cell behaviour.

How challenging were the experiments in the paper—both in terms of building or standardizing the model, and in the day-to-day logistics?

Mouse gastruloids are a well-established and robust model system, and they were already up and running in the Trivedi Lab when I joined. Thanks to that, it was quite straightforward for me to start working with them. But I did get great help from others in the lab, especially during revisions. So, it was really a team effort.

What are your upcoming plans – what questions are you excited to pursue in future?

I am currently trying to put together an enthusiastic team and tackle some of the questions I am really excited about: 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? We’ll definitely keep an eye on glycolysis, but I’m also really keen to explore other metabolic pathways and see what else we can discover.

What role does curiosity play in your life, both within and outside of science? How important it is for you to answer basic science questions?

I would say that being curious is one of my most important character trait, and I really cherish it. It’s what drives me to explore new people, cultures, places, and ideas. When it comes to basic science questions, I think curiosity is absolutely essential, since you can’t always rely on other motivations, such as direct applications to human health. For me, basic science questions are usually the most exciting ones, and I wouldn’t want to work on anything that doesn’t truly fascinate me. I guess it comes from the longing to understand how life works. How can that not be exciting J?

How can insights from understanding basic science aspects of early development help us understand the impact of maternal nutrition and metabolic microenvironment on embryonic health and the risk of congenital/metabolic disorders in humans?

I think understanding basic science aspects of early development is absolutely crucial to understand the impact of the nutritional environment on embryonic development on a molecular level. We know since a long time that the maternal nutrition impacts even early stages of embryonic development. What we often don’t understand are the phenotypes and their underlying mechanisms. So, it’s important to support basic science on early development to better understand what goes wrong in suboptimal nutritional environments or during metabolic disorders.

Tell us about how you see the future of developmental metabolism and cell fate evolve with the new upcoming tools.

Development happens in time and space, so I believe that visualizing metabolic dynamics is essential for better understanding the role of metabolism during development. Techniques like spatial metabolomics and the use of biosensors will be incredibly valuable for this purpose.

I’m also really excited about the development of new tools that allow us to manipulate metabolic pathways in a spatiotemporal manner. In my recent work, I developed a genetic tool to restrict glucose availability by leveraging a sucrose-cleaving enzyme from yeast, and I’m eager to further refine and expand this approach in the future.

Were there any pivotal moments that shaped your career path? What’s an unexpected place you’ve found inspiration for your work? What advice would you offer to students and early-career scientists interested in exploring the intersections of metabolism and cell fate regulation?

One pivotal moment was seeing a zebrafish embryo develop during an undergraduate course (thank you, @Gerrit Begemann!). It was so beautiful and fascinating that I immediately wanted to understand how something like that works.

Not sure, whether there is an unexpected place but I like to think about things I don’t understand (including science) when I am moving between places, especially while cycling. Maybe it’s something about being in motion.

For students early-career scientists and actually everyone interested in the intersection of metabolism and cell fate regulation, my advice is to seek as much feedback as possible on your ideas and work. This is a complex and rapidly evolving field, and most of us were trained primarily in either developmental biology or metabolism, but rarely both. Engaging with experts from different backgrounds can really broaden your perspective and strengthen your research.

How do you maintain a balance between your rigorous research activities and personal life?

I really like to do outdoor sports, such as rock climbing and beach volleyball. It helps me to clear my head. 

If you hadn’t embarked on a career in biological research, what other profession might you have pursued, and why?

That’s a tough question—I really love what I do! But if I hadn’t gone into biological research, I think I’d still want a career where I’m surrounded by smart, creative people and constantly learning new things. Whether it was in education, technology, or even the arts, the most important thing for me would be working in an environment that challenges me intellectually and encourages curiosity.

Anything you’d want to highlight for the future !

Yes, I actually will be starting my lab at IMBA Vienna in September! We’ll be looking at environmental and metabolic regulators of embryonic development. There is more info on our website (https://www.oeaw.ac.at/imba/groups/kristina-stapornwongkul). So please reach out if you feel enthusiastic to join the team!

Previously we learnt about the role of metabolism in seasonal adaptations and phenotypic plasticity using two unique insect models – butterflies and budworms. Check out – The season’s script: Tales of Metabolic adaptation (Karin Van Der Burg).

Check out the article All the world’s a metabolic dance, and how early career scientists are leading the way !!

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