Design and simulation of computational models of the DNA replication dynamics in kinetoplastids

Abstract

DNA replication in eukaryotic cells is essentially a parallelized process, which is started multiple times during S phase in cell cycle at sites known as "replication origins". However, the dynamics underlying this process is subjected to a number of factors, including the start frequency of each origin and occasional collisions between the molecular machineries responsible for replication and transcription. A current hypothesis is that this dynamics is responsible for genomic architecture differences among Trypanosoma cruzi and other kinetoplastids. To further investigate this question, we propose in this project the creation of a stochastic computational model to allow the study of dynamical properties of replication in T. cruzi, especially regarding attributes of the collisions that happen during this process. This computational model will be designed using Markov chains, implemented in Python and adjusted through biological data produced at our laboratory and also information available in the literature. By simulating the model in various conditions, we expect to find relevant properties regarding DNA replication in T. cruzi and, in a second stage, also in other kinetoplastids and in yeast. (AU)