MBI PhD Oral Defense

Time: 1pm
Date: Friday, 12 October 2018
Venue: MBI, level 5 meeting rooms

Supervisor: Prof Timothy Saunders (Main supervisor)

Decoding morphogen-instructed developmental precision

by Huang Anqi, Saunders Group

Animal development is robust, as nature reiterates to us. How does developmental process achieve its precision and reproducibility and what are the underlying mechanisms? This is perhaps one of the most principal and longstanding questions in the life sciences. The title of this thesis, Decoding morphogen-instructed developmental precision, states its task: to answer the question, “how is developmental precision intrinsically encoded within the way cells interpret morphogens” – one of the most pervasive mechanisms of developmental pattern formation across all organisms.

The first major theme of this thesis is to dissect the time-dependent interpretation of morphogen-encoded information by cells in developing embryos. Using the morphogen Bicoid in early Drosophila embryo as a model system, an optogenetic technique to temporally manipulate Bicoid transcriptional activity is developed. It is observed that cells instructed by higher morphogen concentration also require morphogen inputs for longer duration in order to reach the correct cell fate decisions, and it has been shown that such temporal non-linearity of morphogen interpretation can be at least partially attributed to differential kinetics of target gene activation.

The second theme of the thesis concerns the loss of developmental precision under decanalized conditions, for example, where morphogen inputs are perturbed. It is argued here that the mechanical properties, such as the embryonic geometry introduces sources of variation into the patterning process, and therefore predetermines the phenotypic outcomes of each perturbed individual.

This thesis demonstrates an urge to use novel experimental techniques to dissect the step-wise decision-making of cells along developmental trajectories. It is not only to continue the traditional effort to visualize the developmental process from a deterministic point of view, but also to link it to the new venture of understanding the complex dynamics of cell states and the self-organization of biological systems.

**Please note the examination following the seminar is closed-door**