• What is the problem/issue being addressed?
We investigate the genetic mechanisms of biological robustness, aiming at deriving broad principles about how animals operate consistently. Biological robustness is a poorly studied phenomenon that has recently attracted a lot of attention both from an experimental and theoretical point of view. We often forget how complicated biological systems are, how many perturbations they constantly face and how much stochasticity there is when looking at the underlying molecular processes. It is therefore rather remarkable that biological systems can operate often with extreme consistency. One such example is development in the simple model nematode Caenorhabditis elegans, which is very stereotypical so that the zygote always produces the same number of 959 cells in a reproducible manner with minimal animal-to-animal variation. The majority of previous studies have been performed in unicellular organisms. We use instead a comprehensive system-wide approach using a tractable multi-cellular model organism to break down development robustness of cell numbers and dissect its mechanisms.
• Why is it important for society?
Although system robustness in non-biology fields such as engineering (e.g. robustness of buildings, bridges, aeroplanes or the internet) is man-made, biological robustness arises from selection or as a by-product of evolution and the underlying mechanisms are very little understood. It is currently unclear whether broad principles can be derived that are important for any type of robustness and whether knowledge from one field can guide thinking or future work in another field (e.g. biologically-inspired engineering). Understanding the basis of biological robustness is a fundamental problem that is relevant to biomedical sciences as a lot of diseases can also be studied within the context of defective homeostasis. New approaches in building synthetic biological networks can be influenced by reaching an understanding on principles of biological robustness.
• What are the overall objectives?
Our project has three main aims. First, to develop a new experimental system to study and systematically quantify developmental robustness in C. elegans. Second, to identify a wide-spectrum of genetic determinants of phenotypic robustness and characterise the mechanisms of biological buffering. Third, to explore how differences in the genetic background for example present in divergent nematode populations may affect developmental system traits including robustness to perturbations.
