Analysis of the impact of ROS in networks describing neurodegenerative diseases

Doctoral thesis (2016)

In the current thesis the model of the ROS management network is built using the domino principle. The model offers insight into the design principles underlying the ROS management network and enlightens ... [more ▼]

In the current thesis the model of the ROS management network is built using the domino principle. The model offers insight into the design principles underlying the ROS management network and enlightens its functionality in the diseases such as cancer and Parkinson’s disease (PD). It is validated using experimental data. The model is used for in silico study of the ROS management dynamics under the stress conditions (oxidative stress). This highlights the phenomena of both adaptation to stress and the stress accumulation effect in case of repeated stress. This study also helps to discover the potential ways to a personalized treatment of the insufficient ROS management. The different ways of a control of the ROS management network are shown using the optimal control approach. Obtained results could be used for a seeking of the treatment strategies to fix the ROS management failures caused by an oxidative stress, neurodegenerative diseases, etc. Or, in vice versa, to develop the ways of a controllable cell death that might be used in cancer research. [less ▲]

ROS homeostasis in a dynamic model: How to save PD neuron?

Poster (2014, December)

ROS-management in Parkinson’s disease: Dynamic blue-print domino-based model and design principles study. Dynamic modelling of ROS management and ROS-induced mitophagy

Poster (2014, October)

ROS-activated signaling network: dynamic modelling and design principles study

Poster (2014, June)

Dynamic modelling of ROS management and ROS-induced mitophagy

Poster (2014, June)

Design principles study of ROS management and ROS-induced mitophagy with a kinetic model

Poster (2013, September 27)

In vivo evidence demonstrates three fundamental interconnected adaptive survival mechanisms , which protect against excessive ROS that is generated during mitochondrial dysfunction: (i) autophagy ... [more ▼]

In vivo evidence demonstrates three fundamental interconnected adaptive survival mechanisms , which protect against excessive ROS that is generated during mitochondrial dysfunction: (i) autophagy/mitophagy, (ii) adaptive antioxidant response and (iii) NFkB signaling in cancer and neurodegeneration. We have been expanding a kinetic model which recapitulates the consensus understanding of the mechanisms responsible for cellular ROS – management system and performed modular analysis to analyze emergent behavior. We started with the simplest model and added stepwise new modules. We identify the qualitative role (certain emergent behavior) attributed to each module and thus understand the design principles of the system. We propose a detailed, mechanistic, kinetic model for studying how mutations relevant for diseases such as PD and cancer affect the emergent behavior of ROS management network. [less ▲]

ROS-induced regulation of mitophagy and its failure in Parkinson’s disease

Poster (2013, May)

Reactive Oxygen Species (ROS) generation is an unavoidable background process in the normal functioning of the cell. The greatest contributor to ROS production is the electron transport chain (ETC) where ... [more ▼]

Reactive Oxygen Species (ROS) generation is an unavoidable background process in the normal functioning of the cell. The greatest contributor to ROS production is the electron transport chain (ETC) where O2 is reduced to H2O. Some incompletely-reduced oxygen species escape and oxidize a variety of organic molecules (e.g. proteins and lipids in the mitochondrial membrane), leading to molecular dysfunction and initiating a positive feedback loop leading to generation of even more active radicals. Increased ROS concentration damages mitochondria and further increases ROS generation. Healthy cells manage ROS enzymatically with superoxide dismutase and other enzymes, various antioxidants, and ultimately through increased mitophagy of damaged mitochondria. The precise tuning of the latter mechanism is crucial for cell survival and is controlled in the cell by a ROS-induced regulatory network, which consists of many components such as Nrf2, Keap1, Parkin and p62 with a rather complicated cross-talk (Figure 1). In many diseases (cancer, Parkinson’s disease (PD), Huntington’s disease (HD), etc.), various components of the ROS management network are altered. Deconstructing the molecular mechanisms underlying or resulting from these alterations might contribute to better understanding of the dynamics of related pathophysiological processes. We have built a kinetics-based model which recapitulates the consensus understanding of the mechanism responsible for cellular ROS – managing system. [less ▲]

Efficient single-photon generator based on entanglement between the emitter and field in a photonic crystal near the band edge

in Optics and Spectroscopy (2010), 108(3), 425-432

The possibility of using the long-lived entangled state between the emitter and field near the band edge of the density of states of a photonic crystal to create an efficient generator of single photons ... [more ▼]

The possibility of using the long-lived entangled state between the emitter and field near the band edge of the density of states of a photonic crystal to create an efficient generator of single photons is considered. The generator can be efficiently excited by incoherent pumping, excludes simultaneous generation of two photons, and ensures a high probability of extracting the photon into a specified mode. [less ▲]

Quantum dynamics of single-photon detection

in Optics and Spectroscopy (2007), 103(1), 121-128

Dynamics of the elementary photoelectric conversion upon interaction of a single-photon mode with a bound electron in a one-dimensional rectangular potential well is considered. The spatial and temporal ... [more ▼]

Dynamics of the elementary photoelectric conversion upon interaction of a single-photon mode with a bound electron in a one-dimensional rectangular potential well is considered. The spatial and temporal dynamics of the wave packet corresponding to a free photoelectron is investigated. [less ▲]