Nonlinearity and stochasticity in biochemical networks

Recent advances in biology have revolutionized our understanding of living systems. For the first time, it is possible to study the behavior of individual cells. This has led to the discovery of many amazing phenomena. For example, cells have developed intelligent mechanisms for foraging, communicating, and responding to environmental changes. These diverse functions in cells are controlled through biochemical networks consisting of many different proteins and signaling molecules. These molecules interact and affect gene expression, which in turn affects protein production. This results in a complex mesh of feedback and feedforward interactions. These complex networks are generally highly nonlinear and stochastic, making them difficult to study quantitatively. Recent studies have shown that biochemical networks are also highly modular, meaning that different parts of the network do not interact strongly with each other. These modules tend to be conserved across species and serve specific biological functions. However, detect- ing modules and identifying their function tends to be a very difficult task. To overcome some of these complexities, I present an alternative modeling approach that builds quantitative models using coarse-grained biological processes. These coarse-grained models are often stochastic (probabilistic) and highly non-linear. In this thesis, I focus on modeling biochemical networks in two distinct biological systems: Dictyostelium discoideum and microRNAs. Chapters 2 and 3 focus on cellular communication in the social amoebae Dictyostelium discoideum. Using universality, I propose a stochastic nonlinear model that describes the behavior of individual cells and cellular populations. In chapter 4 I study the interaction between messenger RNAs and noncoding RNAs, using Langevin equations

Design of novel chemical oscillators

Designing new chemical and/or electrochemical oscillatory systems is an important area in nonlinear chemical dynamics. We successfully designed two new chemical oscillators, the pyrocatechol-bromate-sulfuric acid and aminophenol-bromate-sulfuric acid systems. Both chemical systems exhibit a very rich oscillatory behavior and we obtained their phase diagrams in uncatalyzed and ferroin-catalyzed systems. Phase diagrams in the bromate - pyrocatechol - sulfuric acid concentration space illustrate that the observed chemical oscillations strongly depend on the ratio of [bromate]/[pyrocatechol] rather than their actual concentrations. Also, in both uncatalyzed and catalyzed systems kinetics and mechanisms have been investigated. In mechanistic studies, we have tried to determine intermediate species with various analytical techniques such as: FTIR., 1H NMR, 13C NMR, Mass spectroscopy, TLC, Elemental Analysis, etc. The aminophenol system is found to be a photo-mediated oscillatory system which does not exhibit spontaneous oscillations in the absence of light. Investigation of the role of illumination, in particular the wavelength of light responsible for the oscillatory behaviour, in the aminophenol-acidic bromate system has been carried out. Study shows that the long induction time in this photochemical oscillator has an exponential dependence on the light intensity. On the other hand, the pyrocatechol system is a photosensitive oscillatory system which light is capable of quenching and inducing oscillation in the system. Furthermore, chemical wave activities in the ferroin-catalyzed pyrocatechol system have been investigated, in 2-dimensional (2-D) beads and homogeneous systems, and in a 1-dimensional (1-D) medium. In the 1-D pyrocatechol system, we observed various types of pulse instabilities such as: breathing, propagation failure, merging pulses, and packing phenomena. In the homogeneous 2-D medium, the pyrocatechol system exhibited two stages of wave activity. Spontaneous transitions to complex spatiotemporal patterns, as a result of anomalous dispersions, have also been observed. In the beads pyrocatechol system, variation of wave propagation speeds and spiral tip trajectories versus four different factors including concentrations of bromate, acid, and ferroin concentration and beads mass have been characterized. Wave studies in the 1-D aminophenol system showed different types of pulse instabilities as well, where global breathing phenomena lasted for more than 48 hours in most cases. In 2-D reaction diffusion media in bead, the ferroin-catalyzed aminophenol system is capable of supporting slow waves even in the absence of light

Optogenetic Brain Interfaces

The brain is a large network of interconnected neurons where each cell functions as a nonlinear processing element. Unraveling the mysteries of information processing in the complex networks of the brain requires versatile neurostimulation and imaging techniques. Optogenetics is a new stimulation method which allows the activity of neurons to be modulated by light. For this purpose, the cell-types of interest are genetically targeted to produce light-sensitive proteins. Once these proteins are expressed, neural activity can be controlled by exposing the cells to light of appropriate wavelengths. Optogenetics provides a unique combination of features, including multimodal control over neural function and genetic targeting of specific cell-types. Together, these versatile features combine to a powerful experimental approach, suitable for the study of the circuitry of psychiatric and neurological disorders. The advent of optogenetics was followed by extensive research aimed to produce new lines of light-sensitive proteins and to develop new technologies: for example, to control the distribution of light inside the brain tissue or to combine optogenetics with other modalities including electrophysiology, electrocorticography, nonlinear microscopy, and functional magnetic resonance imaging. In this paper, the authors review some of the recent advances in the field of optogenetics and related technologies and provide their vision for the future of the field.United States. Defense Advanced Research Projects Agency (Space and Naval Warfare Systems Center, Pacific Grant/Contract No. N66001-12-C-4025)University of Wisconsin--Madison (Research growth initiative; grant 101X254)University of Wisconsin--Madison (Research growth initiative; grant 101X172)University of Wisconsin--Madison (Research growth initiative; grant 101X213)National Science Foundation (U.S.) (MRSEC DMR-0819762)National Science Foundation (U.S.) (NSF CAREER CBET-1253890)National Institutes of Health (U.S.) (NIH/NIBIB R00 Award (4R00EB008738)National Institutes of Health (U.S.) (NIH Director’s New Innovator award (1-DP2-OD002989))Okawa Foundation (Research Grant Award)National Institutes of Health (U.S.) (NIH Director’s New Innovator Award (1DP2OD007265))National Science Foundation (U.S.) (NSF CAREER Award (1056008)Alfred P. Sloan Foundation (Fellowship)Human Frontier Science Program (Strasbourg, France) (Grant No. 1351/12)Israeli Centers of Research Excellence (I-CORE grant, program 51/11)MINERVA Foundation (Germany

Investigations of surface plasmon resonances by energy-filtering transmission electron microscopy methods

This thesis concentrates on different plasmonic phenomena which are observed with a transmission electron microscope (TEM) in combination with electron energy loss spectroscopy (EELS) and energy-filtering transmission electron microscopy (EFTEM) techniques offering high energy and spatial resolution. Plasmonic coupling behaviour of nanoholes and nanoparticles having rectangular, circular, triangular etc. shapes were investigated using different techniques. The electromagnetic nature of the observed situations was unveiled with different simulation techniques based on discrete dipole approximation (DDA), finite element method (FEM), and three-dimensional finite-difference time-domain methods (3D-FDTD)