A DNA network as an information processing system.

Biomolecular systems that can process information are sought for computational applications, because of their potential for parallelism and miniaturization and because their biocompatibility also makes them suitable for future biomedical applications. DNA has been used to design machines, motors, finite automata, logic gates, reaction networks and logic programs, amongst many other structures and dynamic behaviours. Here we design and program a synthetic DNA network to implement computational paradigms abstracted from cellular regulatory networks. These show information processing properties that are desirable in artificial, engineered molecular systems, including robustness of the output in relation to different sources of variation. We show the results of numerical simulations of the dynamic behaviour of the network and preliminary experimental analysis of its main components.

Integrative network modeling reveals mechanisms underlying T cell exhaustion.

Failure to clear antigens causes CD8+ T cells to become increasingly hypo-functional, a state known as exhaustion. We combined manually extracted information from published literature with gene expression data from diverse model systems to infer a set of molecular regulatory interactions that underpin exhaustion. Topological analysis and simulation modeling of the network suggests CD8+ T cells undergo 2 major transitions in state following stimulation. The time cells spend in the earlier pro-memory/proliferative (PP) state is a fixed and inherent property of the network structure. Transition to the second state is necessary for exhaustion. Combining insights from network topology analysis and simulation modeling, we predict the extent to which each node in our network drives cells towards an exhausted state. We demonstrate the utility of our approach by experimentally testing the prediction that drug-induced interference with EZH2 function increases the proportion of pro-memory/proliferative cells in the early days post-activation.

Investigating the properties of self-organization and synchronization in electronic systems.

Nonlinear cooperative behavior appears naturally in many systems, such as cardiac cell oscillations; cellular calcium oscillations; oscillatory chemical reactions, and fireflies. Such systems have been studied in detail due to their inherent properties of robustness, adaptability, scalability, and emergence. In this paper, such nonlinear cooperative behaviors are considered within the domain of electronic system design. We investigate these desirable properties in a system composed of electronic oscillators. The paper presents a series of circuit simulation results showing that self-organizing principles, which can be emulated in an electronic circuit, enable the systems to show a phase transition to synchronization, in a manner similar to those of natural systems. Circuit simulation results presented here show that the circuits are robust to the unreliable performance of the electronic oscillators and tolerant to their run-time faults. These are important findings for future engineering applications in which the system's elements are likely to be unreliable and faulty, such as in molecular- and nanoelectronic systems.

The manipulation of calcium oscillations by harnessing self-organisation.

This paper investigates how self-organisation might be harnessed for the manipulation and control of calcium oscillations. Calcium signalling mechanisms are responsible for a number of important functions within biological systems, such as fertilization, secretion, contraction, neuronal signalling and learning. In this paper, calcium oscillations are investigated as a biological periodic process. Within biological systems such periodic behaviour is one of the outcomes from self-organisation. The understanding of periodic processes in living systems can enable more accurate diagnosis and physiologically suitable clinical therapies to be proposed, for diseases such as cancer, epilepsy, cardiac diseases and other dynamic diseases. In this paper these ideas are investigated by means of the calcium-induced calcium release (CICR) model and a number of representative simulations of intra and inter-cellular calcium oscillations are used to illustrate the manipulation and control of these oscillations in normal and pathological situations.