A Framework for In-Network Management in Heterogeneous Future Communication Networks

Future communication networks will be composed of a diversity of highly heterogeneous network variants, ranging from energy constrained wireless sensor networks to large-scale wide area networks. The fact that the size and complexity of such networks will experience tremendous growth will eventually render existing traditional network management paradigms unfeasible. We propose the radically new paradigm of in-network management, which targets the embedding of self-management capabilities deep inside the network nodes. In this paper, we focus on our framework for in-network management, which allows management logic to be embedded and executed within network nodes. Based on a specific use-case of bio-inspired network management, we demonstrate how our framework can be exploited in a network failure scenario using quorum sensing and chemotaxis

Programming microbes to treat superbug infection

Superbug infection is one of the greatest public health threat with grave implications across all levels of society. Towards a new solution to combat infection by multi-drug resistant bacteria, this thesis presents an engineering framework and genetic tools applied to repurpose commensal bacteria into “micro-robots” for the treatment of superbug infection. Specifically, a prototype of designer probiotic was developed using the human commensal bacteria Escherichia coli. The engineered commensal was reprogrammed with user-specified functions to sense superbug, produced pathogen-specific killing molecules and released the killing molecules via a lytic mechanism. The engineered commensal was effective in suppressing ~99% of planktonic Pseudomonas and preventing ~ 90% of biofilm formation. To enhance the sensing capabilities of engineered commensal, genetic interfaces comprising orthogonal AND & OR logic devices were developed to mediate the integration and interpretation of binary input signals. Finally, AND, OR and NOT logic gates were networked to generate a myriad of cellular logic operations including half adder and half subtractor. The creation of half adder logic represents a significant advancement of engineering human commensal to be biological equivalent of microprocessor chips in programmable computer with the ability to process input signals into diversified actions. Importantly, this thesis provides exemplary case studies to the attenuation of cellular and genetic context dependent effects through principles elucidated herein, thereby advancing our capability to engineer commensal bacteria.Open Acces

A survey of molecular communication in cell biology : establishing a new hierarchy for interdisciplinary applications

Molecular communication (MC) engineering is inspired by the use of chemical signals as information carriers in cell biology. The biological nature of chemical signaling makes MC a promising methodology for interdisciplinary applications requiring communication between cells and other microscale devices. However, since the life sciences and communications engineering fields have distinct approaches to formulating and solving research problems, the mismatch between them can hinder the translation of research results and impede the development and implementation of interdisciplinary solutions. To bridge this gap, this survey proposes a novel communication hierarchy for MC signaling in cell biology and maps phenomena, contributions, and problems to the hierarchy. The hierarchy includes: 1) the physical propagation of cell signaling at the Physical Signal Propagation level; 2) the generation, reception, and biochemical pathways of molecular signals at the Physical and Chemical Signal Interaction level; 3) the quantification of physical signals, including macroscale observation and control methods, and conversion of signals to information at the Signal-Data Interface level; 4) the interpretation of information in cell signals and the realization of synthetic systems to store, process, and communicate molecular signals at the Local Data Abstraction level; and 5) applications relying on communication with MC signals at the Application level. To further demonstrate the proposed hierarchy, it is applied to case studies on quorum sensing, neuronal signaling, and communication via DNA. Finally, several open problems are identified for each level and the integration of multiple levels. The proposed hierarchy provides language for communication engineers to study and interface with biological systems, and also helps biologists to understand how communications engineering concepts can be exploited to interpret, control, and manipulate signaling in cell biology

From Microbial Communities to Distributed Computing Systems

A distributed biological system can be defined as a system whose components are located in different subpopulations, which communicate and coordinate their actions through interpopulation messages and interactions. We see that distributed systems are pervasive in nature, performing computation across all scales, from microbial communities to a flock of birds. We often observe that information processing within communities exhibits a complexity far greater than any single organism. Synthetic biology is an area of research which aims to design and build synthetic biological machines from biological parts to perform a defined function, in a manner similar to the engineering disciplines. However, the field has reached a bottleneck in the complexity of the genetic networks that we can implement using monocultures, facing constraints from metabolic burden and genetic interference. This makes building distributed biological systems an attractive prospect for synthetic biology that would alleviate these constraints and allow us to expand the applications of our systems into areas including complex biosensing and diagnostic tools, bioprocess control and the monitoring of industrial processes. In this review we will discuss the fundamental limitations we face when engineering functionality with a monoculture, and the key areas where distributed systems can provide an advantage. We cite evidence from natural systems that support arguments in favor of distributed systems to overcome the limitations of monocultures. Following this we conduct a comprehensive overview of the synthetic communities that have been built to date, and the components that have been used. The potential computational capabilities of communities are discussed, along with some of the applications that these will be useful for. We discuss some of the challenges with building co-cultures, including the problem of competitive exclusion and maintenance of desired community composition. Finally, we assess computational frameworks currently available to aide in the design of microbial communities and identify areas where we lack the necessary tool

A survey on engineering approaches for self-adaptive systems (extended version)

The complexity of information systems is increasing in recent years, leading to increased effort for maintenance and configuration. Self-adaptive systems (SASs) address this issue. Due to new computing trends, such as pervasive computing, miniaturization of IT leads to mobile devices with the emerging need for context adaptation. Therefore, it is beneficial that devices are able to adapt context. Hence, we propose to extend the definition of SASs and include context adaptation. This paper presents a taxonomy of self-adaptation and a survey on engineering SASs. Based on the taxonomy and the survey, we motivate a new perspective on SAS including context adaptation

Engineering Complex Computational Ecosystems

Self-organising pervasive ecosystems of devices are set to become a major vehicle for delivering infrastructure and end-user services. The inherent complexity of such systems poses new challenges to those who want to dominate it by applying the principles of engineering. The recent growth in number and distribution of devices with decent computational and communicational abilities, that suddenly accelerated with the massive diffusion of smartphones and tablets, is delivering a world with a much higher density of devices in space. Also, communication technologies seem to be focussing on short-range device-to-device (P2P) interactions, with technologies such as Bluetooth and Near-Field Communication gaining greater adoption. Locality and situatedness become key to providing the best possible experience to users, and the classic model of a centralised, enormously powerful server gathering and processing data becomes less and less efficient with device density. Accomplishing complex global tasks without a centralised controller responsible of aggregating data, however, is a challenging task. In particular, there is a local-to-global issue that makes the application of engineering principles challenging at least: designing device-local programs that, through interaction, guarantee a certain global service level. In this thesis, we first analyse the state of the art in coordination systems, then motivate the work by describing the main issues of pre-existing tools and practices and identifying the improvements that would benefit the design of such complex software ecosystems. The contribution can be divided in three main branches. First, we introduce a novel simulation toolchain for pervasive ecosystems, designed for allowing good expressiveness still retaining high performance. Second, we leverage existing coordination models and patterns in order to create new spatial structures. Third, we introduce a novel language, based on the existing ``Field Calculus'' and integrated with the aforementioned toolchain, designed to be usable for practical aggregate programming

Understanding the molecular mechanism through which aspirated bile triggers chronic Pseudomonas aeruginosa infections in respiratory disease

The opportunistic pathogen Pseudomonas aeruginosa is the leading cause of morbidity and mortality in Cystic Fibrosis (CF) patients. Extensive genomic adaptation of this organism facilitates its emergence as a dominant organism within the lung microbial community and to its ability to chronically persist within the CF airways. The environmental and host factors contributing to the success of this species in vivo have been the subject of intensive research efforts. Gastro-oesophageal reflux (GOR) has recently emerged as a major co-morbidity in CF and a range of other respiratory conditions and is associated with the presence of bile acids in the lungs of CF patients, a consequence of micro-aspiration of refluxed gastric contents. This thesis aimed to investigate the impact that bile exerts on the global lung microbiota and the key CF associated pathogen P. aeruginosa. The detection of bile acids in paediatric CF patients using liquid chromatography mass spectrometry (LC-MS) analysis correlated with a reduction in lung microbial biodiversity and the emergence of dominant respiratory pathogens including P. aeruginosa. Bile acids may contribute to the progressive restructuring of the lung microbiota towards a pathogen dominated state associated with worse clinical outcomes. Bile and the active component bile acids were found to be capable of triggering P. aeruginosa to transition to a chronic, antibiotic tolerant lifestyle through a combination of transcriptional and phenotypic responses. Functional screens based on biofilm formation and growth on bile identified key two component systems mediating the biofilm response to bile with a connection to central metabolism becoming apparent. The latter screen identified the glyoxylate shunt as a key breakpoint in the suppression of redox potential as part of the bile response. Bile was also found to be capable of selecting for genetic variants in an in vitro system known to mimic conditions found within the CF lung environment. Pigmented derivatives emerged exclusively in the presence of bile with genome sequencing identifying single nucleotide polymorphisms (SNPs) in quorum sensing (lasR) and both the pyocyanin (phzS) and pyomelanin (hmgA) biosynthetic pathways. These mutations have been previously described in various clinical isolates of P. aeruginosa. Loss of Pseudomonas Quinolone Signal (PQS) production in the pigmented variants underpinned the loss of redox suppression in response to bile, perhaps a consequence of the anti-oxidant/pro-oxidant activities attributed to the PQS signalling molecule. Bile is therefore capable of influencing the evolutionary trajectory of this respiratory pathogen, a key finding in understanding the emergence of genotypic and phenotypic heterogeneity within the lungs of patients with respiratory disease. Collectively, this research supports the role for bile in the progression of chronic infection in CF through its impact on P. aeruginosa and other respiratory pathogens. Therefore, the early detection and profiling of bile acids utilising rapid point of care devices could lead to the identification of high risk paediatric patients and to the development of increasingly effective intervention strategies to prevent the establishment of chronic respiratory microbiota