Fueling embryology and developing metabolism

By Carlos Carmona-Fontaine and Patricia Nunes

Most scientific conferences have become large gatherings where little exchange of ideas can actually occur. There are way too many people to start socializing with folks you don’t know and there are so many talks that the idea of sitting through one on a topic on which you are not an expert sounds suicidal. At the other extreme was The Company of Biologists’ “Metabolism in Development and Disease” Workshop. Within a Downtown Abbey-like XVI century house, a few dozen scientists, including early career ones like us, met to discuss the implications of cell metabolism in embryonic development, immune response and disease – particularly cancer.

It was excellent. And not only because of the impressive Wiston House and its surroundings or the great list of invited speakers. It was excellent because this was a true instance where people from disparate fields met, exchanged ideas and learnt from each other. We were no exception -as our backgrounds testify. Patricia is a biochemist that has always worked on metabolism while Carlos is a developmental biologist by training. As early career scientists, it was incredibly exciting to meet and discuss with more seasoned researchers in an open and intimate environment. The pastoral fields that surrounded Wiston House and the only bar of the neighborhood, conveniently located in the same house, also helped to foster friendship and possible collaborations with fellow junior and senior biologists alike.

The talks were excellent too. There will be an upcoming meeting report to be published in Development (by Aurelio Teleman) that will summarize some of the scientific content of the meeting, so we will focus more on our personal take on the lessons from the meeting. Molecular biologists have pushed for an understanding of cellular functions based on signal transduction and codes – a visionary idea. For example, the conceptualization of the Central Dogma powered by people like Francis Crick and Sydney Brenner was a milestone in the history of molecular biology. It allowed us to simplify the complexity of cellular activities and think them as signaling problems. This concept helped us greatly to advance our understanding of how cells function and interact with each other. This is similar to how graphical interfaces and operating systems have eased the use of computers, as we do not need to deal with abstract programs and complicated coding anymore. There is a downside to this approach however: we could forget how computers actually work. Similarly, we sometimes forget that “cell markers” are enzymes, or nutrient transporters or pH and oxygen sensors. Transcription factors are critical for the development of the embryo (or a tumor) but they are that way because they ultimately encode for functional proteins that direct specific chemical reactions – such as RNA synthesis – in the cell. Why don’t we think where the methyl or acetyl groups are coming from when we talk about histone modifications and the “epigenetic code”? We risk biasing our understanding of cell biology as a collection of codes and signals, rather than actual chemical reactions.

The field of cell metabolism is inherently linked with a more biochemical understanding of biological functions. For the last two decades, this field has been reinvigorated by advances in molecular biology and modern genetics.
This synergy has been adopted by a vast number of scientists working in immunology, cancer and many other research fields. Although modern metabolism has also begun to permeate developmental biology, we think that this workshop was absolutely unique and marks the milestone of a hopefully long-lasting interaction between embryology and metabolism. In this meeting, it was clear that the field of development reciprocated with its emphasis on spatial compartmentalization and temporal dynamics of cell metabolism. For example, it was exciting to learn about the efforts to develop and improve machines that allow the detection of metabolites and stable isotopes with a 50nm resolution! We also discussed how nutrients can mediate cell-cell interactions and allow for mutualistic or competitive cell relationships. There is still a long road ahead and these research fields need to cooperate to develop new and better tools to probe complex metabolic systems. For example, promising technologies such as optogenetics will clearly help us to “shine light” onto as yet unknown metabolic networks within and between cells. Although regulation of metabolic networks in certain diseases may sound futuristic, it may well be a crucial step to develop successful personalized therapies – though as we said it’s a long road!

At the end of the workshop we left with a feeling that cell signals are a key way to understand cell biology, but we cannot forget that ultimately life is about growing and growth requires a exquisite regulation of its basic components: metabolites.

We thank Ben Steventon and Katherine Brown for comments on the text.

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