Faithful modeling of transient expression and its application to elucidating negative feedback regulation
Modeling and analysis of genetic regulatory networks is essential both for better understanding their dynamic behavior and for elucidating and refining open issues. We hereby present a discrete computational model that effectively describes the transient and sequential expression of a network of genes in a representative developmental pathway. Our model system is a transcriptional cascade that includes positive and negative feedback loops directing the initiation and progression through meiosis in budding yeast. The computational model allows qualitative analysis of the transcription of early meiosis-specific genes, specifically, Ime2 and their master activator, Ime1. The simulations demonstrate a robust transcriptional behavior with respect to the initial levels of Ime1 and Ime2. The computational results were verified experimentally by deleting various genes and by changing initial conditions. The model has a strong predictive aspect, and it provides insights into how to distinguish among and reason about alternative hypotheses concerning the mode by which negative regulation through Ime1 and Ime2 is accomplished. Some predictions were validated experimentally, for instance, showing that the decline in the transcription of IME1 depends on Rpd3, which is recruited by Ime1 to its promoter. Finally, this general model promotes the analysis of systems that are devoid of consistent quantitative data, as is often the case, and it can be easily adapted to other developmental pathways.
Date: 2008-Oct-30 Time: 15:00:00 Room: 336
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Workshop “Metabolism and mathematical models: Two for a tango” – 2nd Edition
Title: Workshop Metabolism and mathematical models: Two for a tango – 2nd Edition
Dates: October 25-26, 2022
Location: This workshop will be held in a virtual way
The topic of this workshop is metabolism in general, with a special focus, although not exclusive, on parasitology. Besides an exploration of the biological, biochemical and biomedical aspects, the workshop will also aim at presenting some of the mathematical modelling, algorithmic theory and software development that have become crucial to explore such aspects.
This workshop is being organised in the context of two projects, both with the Inria European Team Erable. One of the projects involves a partnership with the University of São Paulo (USP), in São Paulo, Brazil, more specifically the Institute of Mathematics and Statistics (IME) and the Institute of Biomedical Sciences – Inria Associated Team Capoeira – and the other involves the Inesc-ID/IST in Portugal, ETH in Zürich and EMBL in Heidelberg – H2020 Twinning Project Olissipo.
The workshop is open to all members of these two projects but also, importantly, to the community in general.
The program and more details are available here.