Yasu Saka did his post-graduate work on the cell cycle in Mitsuhiro Yanagida’s lab, Kyoto University, Japan. In 1996, he joined Jim Smith’s lab in the National Institute for Medical Research, London, UK as a post-doc, working on the mechanism of mesoderm formation in Xenopus embryos. He moved to the Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, as Jim became the chairman of the institute. He moved to Lille, France in 2006 as a group leader at the Interdisciplinary Research Institute CNRS. He joined the University of Aberdeen in January 2010.
Our main interest is the pattern formation in animal development. Many different kinds of cells in the body of animals, including humans, are formed in the right place in the right time during embryogenesis. Large numbers of cells in the embryo act in concert to form tissues like skin, muscle or liver. Surprisingly, embryogenesis is a self-organising process and does not require any instructions from outside of the embryo. In other words, embryos 'know how to behave without being told'. How does this happen? How do cells behave as a collective and self-organize into tissues and organs during embryogenesis?
We aim to answer these questions by using novel approaches: the 'Synthetic Developmental Biology'. We formulate mathematical models that are simple yet reproduce the complex pattern formation in the embryo. To test our models we also design and engineer synthetic multi-cellular system using the yeast S.cerevisiae. Such engineered system, unlike natural embryos, is flexible and allows re-designing to test various predictions from different mathematical models. Our work would provide a new perspective to embryogenesis and pattern formation. This in turn may lead to new techniques in regenerative medicine and in other fields of biotechnology.
Recent research highlights include:
We have developed a simple mathematical model of kinetochore–microtubule interactions during cell division. The model shows that the balance between attachment and detachment probabilities of kinetochore microtubules is crucial for correct chromosome bi-orientation. It reveals that chromosome bi-orientation is a probabilistic self-organisation, rather than a sophisticated process of error detection and correction.
We have created a series of Gateway shuttle vectors and an integration vector, which facilitate the assembly of artificial genes and their expression in the budding yeast Saccharomyces cerevisiae. Our method enables the rapid construction of an artificial gene from a promoter and an open reading frame (ORF) cassette by one-step recombination reaction in vitro. Furthermore, the plasmid thus created can readily be introduced into yeast cells to test the assembled gene’s functionality.
The community effect is an interaction among a group of many nearby precursor cells, and is necessary for them to maintain tissue-specific gene expression and differentiate in a coordinated manner. The mechanism of the community effect revealed by our theoretical analysis is analogous to that of quorum sensing in bacteria. The community effect may underlie the size control in animal development and the genesis of autosomal dominant diseases including tumorigenesis.
We investigated roles of a community effect theoretically in two processes of self-organized patterning by diffusible factors: Turing’s reaction-diffusion system and embryonic induction by morphogens. In Turing’s reaction-diffusion system with a built-in community effect, if induction is localized, sustained activation also remains localized. In a model of embryonic induction by a morphogen, gene expression pattern with a well-demarcated boundary emerges. Surprisingly, even when the morphogen distribution eventually becomes uniform, the system can maintain the pattern. The regulatory network thus confers memory of morphogen dynamics.
Our research is supported by Scottish Universities Life Science Alliances (SULSA)