DNA as a universal substrate for chemical kinetics

Molecular programming aims to systematically engineer molecular and chemical systems of autonomous function and ever-increasing complexity. A key goal is to develop embedded control circuitry within a chemical system to direct molecular events. Here we show that systems of DNA molecules can be constructed that closely approximate the dynamic behavior of arbitrary systems of coupled chemical reactions. By using strand displacement reactions as a primitive, we construct reaction cascades with effectively unimolecular and bimolecular kinetics. Our construction allows individual reactions to be coupled in arbitrary ways such that reactants can participate in multiple reactions simultaneously, reproducing the desired dynamical properties. Thus arbitrary systems of chemical equations can be compiled into real chemical systems. We illustrate our method on the Lotka–Volterra oscillator, a limit-cycle oscillator, a chaotic system, and systems implementing feedback digital logic and algorithmic behavior

Engineering ligand-responsive RNA controllers in yeast through the assembly of RNase III tuning modules

The programming of cellular networks to achieve new biological functions depends on the development of genetic tools that link the presence of a molecular signal to gene-regulatory activity. Recently, a set of engineered RNA controllers was described that enabled predictable tuning of gene expression in the yeast Saccharomyces cerevisiae through directed cleavage of transcripts by an RNase III enzyme, Rnt1p. Here, we describe a strategy for building a new class of RNA sensing-actuation devices based on direct integration of RNA aptamers into a region of the Rnt1p hairpin that modulates Rnt1p cleavage rates. We demonstrate that ligand binding to the integrated aptamer domain is associated with a structural change sufficient to inhibit Rnt1p processing. Three tuning strategies based on the incorporation of different functional modules into the Rnt1p switch platform were demonstrated to optimize switch dynamics and ligand responsiveness. We further demonstrated that these tuning modules can be implemented combinatorially in a predictable manner to further improve the regulatory response properties of the switch. The modularity and tunability of the Rnt1p switch platform will allow for rapid optimization and tailoring of this gene control device, thus providing a useful tool for the design of complex genetic networks in yeast

Monostability and multistability of genetic regulatory networks with different types of regulation functions

The official published version of the article can be found at the link below.Monostability and multistability are proven to be two important topics in synthesis biology and system biology. In this paper, both monostability and multistability are analyzed in a unified framework by applying control theory and mathematical tools. The genetic regulatory networks (GRNs) with multiple time-varying delays and different types of regulation functions are considered. By putting forward a general sector-like regulation function and utilizing up-to-date techniques, a novel Lyapunov–Krasovskii functional is introduced for achieving delay dependence to ensure less conservatism. A new condition is then proposed for the general stability of a GRN in the form of linear matrix inequalities (LMIs) that are dependent on the upper and lower bounds of the delays. Our general stability conditions are applicable to several frequently used regulation functions. It is shown that the existing results for monostability of GRNs are special cases of our main results. Five examples are employed to illustrate the applicability and usefulness of the developed theoretical results.This work was supported in part by the Biotechnology and Biological Sciences Research Council (BBSRC) of the U.K. under Grant BB/C506264/1, the Royal Society of the U.K., the National Natural Science Foundation of China under Grants 60504008 and 60804028, the Program for New Century Excellent Talents in Universities of China, and the Alexander von Humboldt Foundation of Germany

Acoustic Communication for Medical Nanorobots

Communication among microscopic robots (nanorobots) can coordinate their activities for biomedical tasks. The feasibility of in vivo ultrasonic communication is evaluated for micron-size robots broadcasting into various types of tissues. Frequencies between 10MHz and 300MHz give the best tradeoff between efficient acoustic generation and attenuation for communication over distances of about 100 microns. Based on these results, we find power available from ambient oxygen and glucose in the bloodstream can readily support communication rates of about 10,000 bits/second between micron-sized robots. We discuss techniques, such as directional acoustic beams, that can increase this rate. The acoustic pressure fields enabling this communication are unlikely to damage nearby tissue, and short bursts at considerably higher power could be of therapeutic use.Comment: added discussion of communication channel capacity in section

Deterministic and stochastic descriptions of gene expression dynamics

A key goal of systems biology is the predictive mathematical description of gene regulatory circuits. Different approaches are used such as deterministic and stochastic models, models that describe cell growth and division explicitly or implicitly etc. Here we consider simple systems of unregulated (constitutive) gene expression and compare different mathematical descriptions systematically to obtain insight into the errors that are introduced by various common approximations such as describing cell growth and division by an effective protein degradation term. In particular, we show that the population average of protein content of a cell exhibits a subtle dependence on the dynamics of growth and division, the specific model for volume growth and the age structure of the population. Nevertheless, the error made by models with implicit cell growth and division is quite small. Furthermore, we compare various models that are partially stochastic to investigate the impact of different sources of (intrinsic) noise. This comparison indicates that different sources of noise (protein synthesis, partitioning in cell division) contribute comparable amounts of noise if protein synthesis is not or only weakly bursty. If protein synthesis is very bursty, the burstiness is the dominant noise source, independent of other details of the model. Finally, we discuss two sources of extrinsic noise: cell-to-cell variations in protein content due to cells being at different stages in the division cycles, which we show to be small (for the protein concentration and, surprisingly, also for the protein copy number per cell) and fluctuations in the growth rate, which can have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012

Complex and unexpected dynamics in simple genetic regulatory networks

Peer reviewedPublisher PD

Malaria and pneumonia effects on rice, vanilla production and rural household income in Madagascar: case of the Sava region

In Madagascar, malaria remains the leading cause of consultation and deaths at hospital at all ages and pneumonia is one of the main causes of the under-five mortality and account for 45% of children hospitalizations. The number of these cases and deaths has not decreased during the last ten years. This paper aims to determine the effects of malaria and pneumonia cases on rice and vanilla production and income. We used data from a cross-sectional survey conducted in 2016  by the authors on 975 rural households and 3,586 individuals of the SAVA region in the northeast of Madagascar. After checking the presence of endogeneity, ordinary least-square method was used instead of two-stage least squares. Our results showed that malaria has no effect on production, and therefore does not affect income. Pneumonia had an effect on production of rice and vanilla. Moreover, the cost of malaria and pneumonia healthcare burdened by households affect their consumption by reducing expenditure on housing. There are many campaigns for the fight against malaria in Madagascar, but pneumonia prevention measures are very rare. Therefore, pneumonia should be considered in the same way as malaria due to its effects on production and investment to fight against these two diseases must be strengthened in order to decrease the costs for the households

Malaria and pneumonia effects on rice, vanilla production and rural household income in Madagascar: case of the Sava region

In Madagascar, malaria remains the leading cause of consultation and deaths at hospital at all ages and pneumonia is one of the main causes of the under-five mortality and account for 45% of children hospitalizations. The number of these cases and deaths has not decreased during the last ten years. This paper aims to determine the effects of malaria and pneumonia cases on rice and vanilla production and income. We used data from a cross-sectional survey conducted in 2016  by the authors on 975 rural households and 3,586 individuals of the SAVA region in the northeast of Madagascar. After checking the presence of endogeneity, ordinary least-square method was used instead of two-stage least squares. Our results showed that malaria has no effect on production, and therefore does not affect income. Pneumonia had an effect on production of rice and vanilla. Moreover, the cost of malaria and pneumonia healthcare burdened by households affect their consumption by reducing expenditure on housing. There are many campaigns for the fight against malaria in Madagascar, but pneumonia prevention measures are very rare. Therefore, pneumonia should be considered in the same way as malaria due to its effects on production and investment to fight against these two diseases must be strengthened in order to decrease the costs for the households

Chemical Power for Microscopic Robots in Capillaries

The power available to microscopic robots (nanorobots) that oxidize bloodstream glucose while aggregated in circumferential rings on capillary walls is evaluated with a numerical model using axial symmetry and time-averaged release of oxygen from passing red blood cells. Robots about one micron in size can produce up to several tens of picowatts, in steady-state, if they fully use oxygen reaching their surface from the blood plasma. Robots with pumps and tanks for onboard oxygen storage could collect oxygen to support burst power demands two to three orders of magnitude larger. We evaluate effects of oxygen depletion and local heating on surrounding tissue. These results give the power constraints when robots rely entirely on ambient available oxygen and identify aspects of the robot design significantly affecting available power. More generally, our numerical model provides an approach to evaluating robot design choices for nanomedicine treatments in and near capillaries.Comment: 28 pages, 7 figure