Speaker
Description
This research project aims to model, calibrate and validate the mechanisms involved in Drosophila´s early development during the pair-rule and, eventually, the segment-polarity phases. With this in mind we will address the morphogenetic interactions during the first two hours of development before cellularisation (Syncythial Phase), anchoring our modelling on the experimental data provided by the FlyEx database.
The gene regulatory network of the Syncythial development phase can be organized into four families of proteins: maternal, gap-gene, pair-rule and segment-polarity. The first class of proteins are transcribed from mRNA of maternal origin and form steady gradients along the anterior-posterior axis of the embryo. The gap-gene proteins give rise to one or two broad domains along the embryo. The pair-rule and segment-polarity gene proteins make the transition to a period structure forming a seven and fourteen stripe pattern, respectively. Two of the most studied pair-rule proteins are the Even-Skipped and Fushi-Tarazu. The positional information provided by their seven bands determine the head, the thoracic segments and the anterior region of the Drosophila´s larvae.
Since the seminal work of Nusslein-Volhard and co-authors, it is assumed that the gradients and segments form due to a mechanism involving protein diffusion and degradation. However, inconsistencies have been found when measuring diffusion coefficients of the maternal protein Bicoid. Moreover, its degradation has never been observed. Later on, it was proposed by Dilão et al. (2009) that gradients could be easily explained under the hypothesis of mRNA diffusion. It was also shown that the primary mechanism of pattern formation could not be explained by diffusion of both proteins and mRNA (R. Dilão, 2014), with the cover of the journal Comptes Rendus Biology 274 (12) (2014) dedicated to this finding.
The main goal will then be to model, calibrate and validate the seven-band structure of Even-Skipped and Fushi-Tarazu proteins and, eventually, for a segment-polarity protein. This model calibration has never been achieved before. This process will consider mutation experiments to identify the set of activators and repressors of each stripe, as they are our main building blocks. Previous modelling for maternal and gap genes will be integrated (F. Alves and R. Dilão, 2006) and it will be assumed that diffusion does not play an important role at the pair-rule stage. A second goal will be to explain the relationship between the Even-Skipped and Fushi-Tarazu patterns, following an inhibitory hypothesis.
Main tasks are as follows:
- Modelling and calibrating the Even-Skipped pair-rule expression based on data without the diffusion hypothesis;
- The relationship between Even-Skipped and Fushi-Tarazu. The inhibitory hypothesis;
- The segment polarity family proteins - hypothetical exploration;
- Discussion of results and thesis writing.
