Projects

Mathematical modelling of neutralization processes of reactive oxygen species in different types of cells

Grant NCN: Preludium 2019/35/N/ST6/04281
Total budget [PLN]: 140 000
Start date: 09/07/2020; End date: 08/07/2022
Status: 15 month/s left

Introduction
Mathematical modelling of processes which neutralize reactive oxygen species in different types of cells Redox reactions (oxidation – reduction) are reactions involving transfer of electrons between two types of molecules. The main participants in cellular redox reactions are reactive oxygen species (ROS) which are recognized as second messengers in overall cell signaling and in stress conditions caused by different factors with irradiation as one of the examples. Therefore the ROS levels have to be strictly regulated. Redox balance is controlled by production of ROS and their neutralization by scavengers (mainly antioxidants). The regulation processes ensure proper cellular functions and metabolism and disturbed balance, called oxidative stress, may lead to cell death or pathology. In my previous research I characterized the ROS levels in cultured cells and their changes after UVA irradiation (Ciesielska et al., 2019) and I discovered that different cell types show different expression of enzymes participating in ROS neutralization. The aim of the present project is to create and use a mathematical model to elucidate the role of different pathways used to neutralize reactive oxygen species by different cell types. The existence of alternative pathways which are used in cells to neutralize ROS and choices made by cells to favor one pathway over another is most probably responsible for the differences in response to the same dose of damaging factor. The same dose of radiation in radiotherapy or exposure to UV may kill some cells and stimulate proliferation of other type cells. Thus identification of the role of ROS neutralizing pathways favored by specific cell types seems to be very important. Such identification of the role of some pathways is not easy in biological experiment but it could be obtained by the mathematical modelling and simulations. Mathematical model based on activation of different neutralization mechanisms was yet not constructed. The original approach together with mathematical model simulations can give new insight into the field of redox balance and as we are constantly exposed to UVA radiation or sometimes to ionizing radiation when radiotherapy is needed, the obtained data concerning neutralization of ROS can even have therapeutic relevance.
Goal
Redox (oxidation –reduction)reactionsarereactions involving transfer of electronsbetweentwo types of molecules[1,2].The main participantsin cellular redox reactions are reactive oxygen species (ROS),which are recognized as second messengers in overall cell signaling and in stress conditions caused by different factorsof whichexposure to radiationis one example[1,3].ROS levelsin cells therefore have to be strictly regulated.Redox balance is controlled by the production of ROS and their neutralization by scavengers (mainly antioxidants).Theseregulation processes areessential for proper cellular functions and metabolism[1]and a disturbed balance, termed oxidative stress, may lead to cellular disorders or death.In my previous research [4] I characterized the ROS levels in cultured cells and their changes after UVA irradiation,and I discovered that different cell typesshow different expression of enzymes participating in neutralizationof ROS
Tasks
Construction and implementation of mathematical modelBiological data acquisitionApplication of biological data to model constructed for different cell types
Contractors

Project manager

Sylwia Ciesielska

Contractors

Results
Articles