Using the coarse-grain mathematical models of DNA mechanics to understand the impact of epigenetic modifications to the function of DNA (DNAmod)

 

Project no.: S-MIP-21-5

Project description:

Epigenetic modifications of DNA play a crucial role in its function, determining gene expression and influencing processes such as development and disease. The understanding of mechanics and function of DNA modifications in normal and cancer cells can help us to identify key nodes for epigenetic intervention. Due to the complexity of the structure of DNA, interdisciplinary approaches, such as bioinformatics tools and mathematical models, need to be employed to understand the effect of physical changes in DNA, caused by its epigenetic modifications. Mathematical modelling is a particularly useful tool to capture structural and dynamical properties of DNA, and to understand the mechanisms of its interactions with proteins.

Based on cgDNA, a coarse-grain model of DNA, we develop mathematical methods to investigate physical mechanisms influenced by DNA epigenetic modifications. Firstly, we study the effect of DNA base cytosine methylation and hydroxymethylation on the structural and biophysical properties of DNA. Secondly, we use the cgDNA model to understand why certain DNA sequences are being preferred by nucleosomes. Further, we extend and apply our modelling framework to quantify and understand the mechanical reasons of CpG islands (the regions of the genome that contain a large number of sites with a cytosine nucleotide followed by a guanine). And finally, we explore the mechanical implications of DNA mutations to the function of DNA. Our theoretical work will be supported by biological evidence and insights from our experimental partner.

Project funding:

Projects funded by the Research Council of Lithuania (RCL), Projects carried out by researchers’ teams

Period of project implementation: 2021-04-01 - 2024-03-31

Project coordinator: Kaunas University of Technology

Project partners: University of Oxford, Ecole Polytechnique Federale de Lausanne (EPFL)

Head:
Daiva Petkevičiūtė-Gerlach

Duration:
2021 - 2024

Department:
Department of Applied Mathematics, Faculty of Mathematics and Natural Sciences