Creating parts that allow for rational design: Synthetic biology and the problem of context-sensitivity

The parts-based engineering approach in synthetic biology aims to create pre-characterised biological parts that can be used for the rational design of novel functional systems. Given the context-sensitivity of biological entities, a key question synthetic biologists have to address is what properties these parts should have so that they give a predictable output even when they are used in different contexts. In the first part of this paper I will analyse some of the answers that synthetic biologists have given to this question and claim that the focus of these answers on parts and their properties does not allow us to tackle the problem of context-sensitivity. In the second part of the paper, I will argue that we might have to abandon the notions of parts and their properties in order to understand how independence in biology could be achieved. Using Robert Cummins’ account of functional analysis, I will then develop the notion of a capacity and its condition space and show how these notions can help to tackle the problem of context-sensitivity in biology.     

Behavioural and neurophysiological evidence for face identity and face emotion processing in animals

Visual cues from faces provide important social information relating to individual identity, sexual attraction and emotional state. Behavioural and neurophysiological studies on both monkeys and sheep have shown that specialized skills and neural systems for processing these complex cues to guide behaviour have evolved in a number of mammals and are not present exclusively in humans. Indeed, there are remarkable similarities in the ways that faces are processed by the brain in humans and other mammalian species. While human studies with brain imaging and gross neurophysiological recording approaches have revealed global aspects of the face-processing network, they cannot investigate how information is encoded by specific neural networks. Single neuron electrophysiological recording approaches in both monkeys and sheep have, however, provided some insights into the neural encoding principles involved and, particularly, the presence of a remarkable degree of high-level encoding even at the level of a specific face. Recent developments that allow simultaneous recordings to be made from many hundreds of individual neurons are also beginning to reveal evidence for global aspects of a population-based code. This review will summarize what we have learned so far from these animal-based studies about the way the mammalian brain processes the faces and the emotions they can communicate, as well as associated capacities such as how identity and emotion cues are dissociated and how face imagery might be generated. It will also try to highlight what questions and advances in knowledge still challenge us in order to provide a complete understanding of just how brain networks perform this complex and important social recognition task.     

Regulation of retroviral RNA export

Viruses are obligate intracellular parasites and have to use the host cell machinery for their replication. Many viruses are able to divert different parts of this machinery to preferentially enhance virus replication at the expense of the cell. The mechanisms by which different viruses do this have, over the years, given us great insight into many cellular processes. Although we still know relatively little about how RNA is exported from the nucleus to the cytoplasm and how this process is regulated, retroviruses have already emerged as one of the most important model systems for these studies. This review will attempt to summarize what we have learnt from these viruses to date and what we hope to achieve in the near future.     

Developmental psychopathology: recent advances and future challenges

The integrative field of developmental psychopathology is having a huge impact on our understanding of human health and behavior. In this paper, I use the example of children's early stress exposure to illustrate how developmental psychopathologists now tend to deemphasize diagnostic categories and, instead, emphasize the social and biological contexts, events and circumstances that have created opportunities for maladaptive responses and health problems in youth. This example shows that developmental psychopathology is increasing understanding of how children develop the abilities that allow them to cope effectively with challenges and what leads to failures in development of these abilities. Integrating research about the neurobiology of learning may prove to be a powerful future direction to understand how the environment regulates behavior. Learning processes become increasingly intricate and fine‐tuned as relevant neuroanatomical systems develop, and as the range, complexity and amount of environmental information increases for the developing child. A focus on these processes allows psychopathologists to formulate questions about which neural mechanisms children use to process information, how these mechanisms are themselves shaped by social context, why adverse social environments confer risk for children, and, perhaps, what sorts of neutrally informed interventions might remediate the deficits in self‐regulation that underlie common psychopathologies.     

Millennial musings on molecular motors

In a universe that is dominated by increasing entropy, living organisms are a curious anomaly. The organization that distinguishes living organisms from their inanimate surroundings relies upon their ability to execute vectorial processes, such as directed movements and the assembly of macromolecules and organelle systems. Many of these phenomena are executed by molecular motors that harness chemical potential energy to perform mechanical work and unidirectional motion. This article explores how these remarkable protein machines might have evolved and what roles they could play in biological and medical research in the coming decades.     

Millennial musings on molecular motors

In a universe that is dominated by increasing entropy, living organisms are a curious anomaly. The organization that distinguishes living organisms from their inanimate surroundings relies upon their ability to execute vectorial processes, such as directed movements and the assembly of macromolecules and organelle systems. Many of these phenomena are executed by molecular motors that harness chemical potential energy to perform mechanical work and unidirectional motion. This article explores how these remarkable protein machines might have evolved and what roles they could play in biological and medical research in the coming decades.     

Millennial musings on molecular motors

In a universe that is dominated by increasing entropy, living organisms are a curious anomaly. The organization that distinguishes living organisms from their inanimate surroundings relies upon their ability to execute vectorial processes, such as directed movements and the assembly of macromolecules and organelle systems. Many of these phenomena are executed by molecular motors that harness chemical potential energy to perform mechanical work and unidirectional motion. This article explores how these remarkable protein machines might have evolved and what roles they could play in biological and medical research in the coming decades.     

How to get to the right place at the right time: Rab/Ypt small GTPases and vesicle transport

Summary Vesicles often must be transported over long distances in a very crowded cytoplasmic environment encumbered by the cytoskeleton and membranes of different origin that provide an important barrier to their free diffusion. In animal cells with specialised tasks, such as neurons or endothelial cells, vesicles that are directed to the cell periphery are linked to the microtubular cytoskeleton tracks via association with motor proteins that allow their vectorial movement. In lower eukaryotes the actin cytoskeleton plays a prominent role in organising vesicle movement during polarised growth and mating. The Ras-like small GTPases of the Rab/Ypt family play an essential role in vesicle trafficking and due to their diversity and specific localisation have long been implicated in the selective delivery of vesicles. Recent evidence has cast doubt on the classical point of view of how this class of proteins acts in vesicle transport and suggests their involvement also in the events that permit vesicle anchoring to the cytoskeleton. Therefore, after a brief review of what is known about how vesicle movement is achieved in mammalian and yeast systems, and how Rab/Ypt proteins regulate the vesicle predocking events, it is discussed how these proteins might participate in the events that lead to vesicle movement through association with the cytoskeleton machinery.     

Perspectives and limitations of resolutions–reconstitution experiments

Reconstitutions of membranous activities can tell us how many components are required and what their functions are. The mitochondrial proton pump is used as an example. Moreover, the biological activity, such as P_i transport, can be used in reconstituted vesicles as an assay during the isolation of the transporter. Reconstitution experiments reveal the importance of membrane asymmetry and allow us to study conditions of vectorial assembly. The mechanism of action of ion pumps has been successfully analyzed in reconstituted liposomes. We can study the movement of ions and the electrogenicity of the system without interference by other unrelated processes. Based on studies with the resolved Ca²⁺-ATPase of sarcoplasmic reticulum, we propose a novel formulation of the mechanism of ATP-driven ion pumps in which cyclic binding of Mg²⁺ plays a key role.     

How to get to the right place at the right time: Rab/Ypt small GTPases and vesicle transport

Vesicles often must be transported over long distances in a very crowded cytoplasmic environment encumbered by the cytoskeleton and membranes of different origin that provide an important barrier to their free diffusion. In animal cells with specialised tasks, such as neurons or endothelial cells, vesicles that are directed to the cell periphery are linked to the microtubular cytoskeleton tracks via association with motor proteins that allow their vectorial movement. In lower eukaryotes the actin cytoskeleton plays a prominent role in organising vesicle movement during polarised growth and mating. The Ras-like small GTPases of the Rab/Ypt family play an essential role in vesicle trafficking and due to their diversity and specific localisation have long been implicated in the selective delivery of vesicles. Recent evidence has cast doubt on the classical point of view of how this class of proteins acts in vesicle transport and suggests their involvement also in the events that permit vesicle anchoring to the cytoskeleton. Therefore, after a brief review of what is known about how vesicle movement is achieved in mammalian and yeast systems, and how Rab/Ypt proteins regulate the vesicle predocking events, it is discussed how these proteins might participate in the events that lead to vesicle movement through association with the cytoskeleton machinery.     

Tunable promoters in systems biology

The construction of synthetic promoter libraries has represented a major breakthrough in systems biology, enabling the subtle tuning of enzyme activities. A number of tools are now available that allow the modulation of gene expression and the detection of changes in expression patterns. But, how does one choose the correct promoter and what are the appropriate methods for reading promoter strength? Furthermore, how fine should the tuning of gene expression be for some specific applications and how can the simultaneous and individual tuning of multiple genes be achieved? Some recent studies have helped us to find answers to many of these questions.     

Migrating shorebirds as integrative sentinels of global environmental change

Many shorebirds travel over large sections of the globe during the course of their annual cycle and use habitats in many different biomes and climate zones. Increasing knowledge of the factors driving variations in shorebird numbers, phenotype and behaviour may allow shorebirds to serve as 'integrative sentinels' of global environmental change. On the basis of numbers, timing of migration, plumage status and body mass, shorebirds could indicate whether ecological and climate systems are generally intact and stable at hemispheric scales, or whether parts of these systems might be changing. To develop this concept, we briefly review the worldwide shorebird migration systems before examining how local weather and global climatic features affect several performance measures of long-distance migrants. What do variations in numbers, phenotype and behaviour tell us about the dependence of shorebirds on weather and climate? How does data on migrating shorebirds integrate global environmental information? Documenting the dependencies between the population processes of shorebirds and global environmental features may be an important step towards assessing the likely effects of projected climate change. In the meantime we can develop the use of aspects of shorebird life histories on large spatial and temporal scales to assay global environmental change.     

A road map for the development of community systems (CoSy) biology

Microbial interactions are essential for all global geochemical cycles and have an important role in human health and disease. Although we possess general knowledge about the major processes within a microbial community, we are presently unable to decipher what role individual microorganisms have and how their individual actions influence others in the community. We also have limited knowledge with which to predict the effects of microbial interactions and community composition on the environment and vice versa. In this Opinion article, we describe how community systems (CoSy) biology will enable us to decode these complex relationships and will therefore improve our understanding of individual members of the community and the modes of interactions in which they engage.     

Metagenomics and biological ontology

Metagenomics is an emerging microbial systems science that is based on the large-scale analysis of the DNA of microbial communities in their natural environments. Studies of metagenomes are revealing the vast scope of biodiversity in a wide range of environments, as well as new functional capacities of individual cells and communities, and the complex evolutionary relationships between them. Our examination of this science focuses on the ontological implications of these studies of metagenomes and metaorganisms, and what they mean for common sense and philosophical understandings of multicellularity, individuality and organism. We show how metagenomics requires us to think in different ways about what human beings are and what their relation to the microbial world is. Metagenomics could also transform the way in which evolutionary processes are understood, with the most basic relationship between cells from both similar and different organisms being far more cooperative and less antagonistic than is widely assumed. In addition to raising fundamental questions about biological ontology, metagenomics generates possibilities for powerful technologies addressed to issues of climate, health and conservation. We conclude with reflections about process-oriented versus entity-oriented analysis in light of current trends towards systems approaches.     

Climate change, biotic interactions and ecosystem services

Climate change is real. The wrangling debates are over, and we now need to move onto a predictive ecology that will allow managers of landscapes and policy makers to adapt to the likely changes in biodiversity over the coming decades. There is ample evidence that ecological responses are already occurring at the individual species (population) level. The challenge is how to synthesize the growing list of such observations with a coherent body of theory that will enable us to predict where and when changes will occur, what the consequences might be for the conservation and sustainable use of biodiversity and what we might do practically in order to maintain those systems in as good condition as possible. It is thus necessary to investigate the effects of climate change at the ecosystem level and to consider novel emergent ecosystems composed of new species assemblages arising from differential rates of range shifts of species. Here, we present current knowledge on the effects of climate change on biotic interactions and ecosystem services supply, and summarize the papers included in this volume. We discuss how resilient ecosystems are in the face of the multiple components that characterize climate change, and suggest which current ecological theories may be used as a starting point to predict ecosystem-level effects of climate change.     

Plastid biogenesis, between light and shadows

Plastids are cellular organelles which originated when a photosynthetic prokaryote was engulfed by the eukaryotic ancestor of green and red algae and land plants. Plastids have diversified in plants from their original function as chloroplasts to fulfil a variety of other roles in metabolite biosynthesis and in storage, or purely to facilitate their own transmission, according to the cell type that harbours them. Therefore cellular development and plastid biogenesis pathways must be closely intertwined. Cell biological, biochemical, and genetic approaches have generated a large body of knowledge on a variety of plastid biogenesis processes. A brief overview of the components and functions of the plastid genetic machinery, the plastid division apparatus, and protein import to and targeting inside the organelle is presented here. However, key areas in which our knowledge is still surprisingly limited remain, and these are also discussed. Chloroplast-defective mutants suggest that a substantial number of important plastid biogenesis proteins are still unknown. Very little is known about how different plastid types differentiate, or about what mechanisms co-ordinate cell growth with plastid growth and division, in order to achieve what is, in photosynthetic cells, a largely constant cellular plastid complement. Further, it seems likely that major, separate plastid and chloroplast 'master switches' exist, as indicated by the co-ordinated gene expression of plastid or chloroplast-specific proteins. Recent insights into each of these developing areas are reviewed. Ultimately, this information should allow us to gain a systems-level understanding of the plastid-related elements of the networks of plant cellular development.     

Using functional morphology to examine the ecology and evolution of specialization

Researchers strive to understand what makes species different,and what allows them to survive in the time and space that theydo. Many models have been advanced which encompass an arrayof ecological, evolutionary, mathematical, and logical principles.The goal has been to develop ecological theories that can, amongother things, make specific and robust predictions about howand where organisms should live and what organisms should utilize.The role of functional morphology is often an under-appreciatedparameter of these models. A more complete understanding ofhow anatomical features work to allow the organism to accomplishcertain tasks has allowed us to revisit some of these ideaswith a new perspective. We illustrate our view of this rolefor functional morphology in ecology by considering the issueof specialization: we attempt to align several definitions ofspecialization based upon shared ecological and evolutionaryprinciples, and we summarize theoretical predictions regardingwhy an organism might specialize. Kinematic studies of preycapture in several types of fishes are explored with regardto the potential ecological and evolutionary consequences ofspecialization, most notably in the area of trade-offs. We suggestthat a functional morphological perspective can increase ourunderstanding of the ecological concepts of specialization andit consequences. The kinds of data that functional morphologistscollect can help us to quantify organismal performance associatedwith specialization and the union of functional morphology withecology can help us to better understand not just how but whyorganisms interact in the manner that they do.     

A climatic basis for microrefugia: the influence of terrain on climate

There is compelling evidence from glacial and interglacial periods of the Quaternary of the utilization of microrefugia. Microrefugia are sites that support locally favorable climates amidst unfavorable regional climates, which allow populations of species to persist outside of their main distributions. Knowledge of the location of microrefugia has important implications for climate change research as it will influence our understanding of the spatial distribution of species through time, their patterns of genetic diversity, and potential dispersal rates in response to climate shifts. Indeed, the implications of microrefugia are profound and yet we know surprisingly little about their climatic basis; what climatic processes can support their subsistence, where they may occur, their climatic traits, and the relevance of these locations for climate change research. Here I examine the climatic basis for microrefugia and assert that the interaction between regional advective influences and local terrain influences will define the distribution and nature of microrefugia. I review the climatic processes that can support their subsistence and from this climatic basis: (1) infer traits of the spatial distribution of microrefugia and how this may change through time; (2) review assertions about their landscape position and what it can tell us about regional climates; and (3) demonstrate an approach to forecasting where microrefugia may occur in the future. This synthesis highlights the importance of landscape physiography in shaping the adaptive response of biota to climate change.