Engineering the bilayer: Emerging genetic tool kits for mechanistic lipid biology

The structural diversity of lipids underpins the biophysical properties of cellular membranes, which vary across all scales of biological organization. Because lipid composition results from complex metabolic and transport pathways, its experimental control has been a major goal of mechanistic membrane biology. Here, we argue that in the wake of synthetic biology, similar metabolic engineering strategies can be applied to control the composition, physicochemical properties, and function of cell membranes. In one emerging area, titratable expression platforms allow for specific and genome-wide alterations in lipid biosynthetic genes, providing analog control over lipidome stoichiometry in membranes. Simultaneously, heterologous expression of biosynthetic genes and pathways has allowed for gain-of-function experiments with diverse lipids in non-native systems. Finally, we highlight future directions for tool development, including recently discovered lipid transport pathways to intracellular lipid pools. Further tool development providing synthetic control of membrane properties can allow biologists to untangle membrane lipid structure-associated functions.     

A conceptual review on systems biology in health and diseases: from biological networks to modern therapeutics

Human physiology is an ensemble of various biological processes spanning from intracellular molecular interactions to the whole body phenotypic response. Systems biology endures to decipher these multi-scale biological networks and bridge the link between genotype to phenotype. The structure and dynamic properties of these networks are responsible for controlling and deciding the phenotypic state of a cell. Several cells and various tissues coordinate together to generate an organ level response which further regulates the ultimate physiological state. The overall network embeds a hierarchical regulatory structure, which when unusually perturbed can lead to undesirable physiological state termed as disease. Here, we treat a disease diagnosis problem analogous to a fault diagnosis problem in engineering systems. Accordingly we review the application of engineering methodologies to address human diseases from systems biological perspective. The review highlights potential networks and modeling approaches used for analyzing human diseases. The application of such analysis is illustrated in the case of cancer and diabetes. We put forth a concept of cell-to-human framework comprising of five modules (data mining, networking, modeling, experimental and validation) for addressing human physiology and diseases based on a paradigm of system level analysis. The review overtly emphasizes on the importance of multi-scale biological networks and subsequent modeling and analysis for drug target identification and designing efficient therapies.     

From trickle to flood: the large-scale,cryptic invasion of California by tropical fruit flies

Since 1954, when the first tropical tephritid fruit fly was detected in California, a total of 17 species in four genera and 11 386 individuals (adults/larvae) have been detected in the state at more than 3348 locations in 330 cities. We conclude from spatial mapping analyses of historical capture patterns and modelling that, despite the 250+ emergency eradication projects that have been directed against these pests by state and federal agencies, a minimum of five and as many as nine or more tephritid species are established and widespread, including the Mediterranean, Mexican and oriental fruit flies, and possibly the peach, guava and melon fruit flies. We outline and discuss the evidence for our conclusions, with particular attention to the incremental, chronic and insidious nature of the invasion, which involves ultra-small, barely detectable populations. We finish by considering the implications of our results for invasion biology and for science-based invasion policy.     

Plant bioregenerative life supports: The Italian CAB Project

Abstract

The Bioregenerative Life Support program CAB (Controllo Ambientale Biorigenerativo) is a key element of the Italian Space Agency (ASI) Medicine & Biotechnology scientific program, set forth in the ASI Activity Plan 2006–2008. The CAB program started in October 2006, under the prime partnership of Thales Alenia Space Italia, with a feasibility study of a controlled biological system, allowing the regeneration of resources and the production of food for life support in long duration missions. Main constituents of the CAB program are: (a) Higher plants as basic elements for food and oxygen production, CO₂ regeneration and water purification via the photosynthetic and leaf transpiration processes, and (b) biological & physico-chemical systems for environmental control, monitoring, power & data distribution, etc. The sectors of technological and scientific concern are practically all the ones typical for life support systems in the frame of long duration human missions; i.e., food production, in particular via the cultivation of higher plants, and food management; air regeneration (production of O₂, removal of CO₂, trace gas control); water regeneration (urine processing, gray water processing, potable water management); solid waste processing; resources allocation and storage; control of environmental conditions (Thermal-hygrometric, light, pressure, radiation, etc).     

Function2Form Bridge—Toward synthetic protein holistic performance prediction

Protein engineering and synthetic biology stand to benefit immensely from recent advances in silico tools for structural and functional analyses of proteins. In the context of designing novel proteins, current in silico tools inform the user on individual parameters of a query protein, with output scores/metrics unique to each parameter. In reality, proteins feature multiple “parts”/functions and modification of a protein aimed at altering a given part, typically has collateral impact on other protein parts. A system for prediction of the combined effect of design parameters on the overall performance of the final protein does not exist. Function2Form Bridge (F2F-Bridge) attempts to address this by combining the scores of different design parameters pertaining to the protein being analyzed into a single easily interpreted output describing overall performance. The strategy comprises of (a) a mathematical strategy combining data from a myriad of in silico tools into an OP-score (a singular score informing on a user-defined overall performance) and (b) the F2F Plot, a graphical means of informing the wetlab biologist holistically on designed construct suitability in the context of multiple parameters, highlighting scope for improvement. F2F predictive output was compared with wetlab data from a range of synthetic proteins designed, built, and tested for this study. Statistical/machine learning approaches for predicting overall performance, for use alongside the F2F plot, were also examined. Comparisons between wetlab performance and F2F predictions demonstrated close and reliable correlations. This user-friendly strategy represents a pivotal enabler in increasing the accessibility of synthetic protein building and de novo protein design.     

The use of digital video recorders in pollination biology

1. Digital video recording (DVR) devices, such as the GoPro Hero, have the potential to greatly benefit pollination ecology, but the advantages of digitally recording pollinator activity over direct human observation have not been formally assessed. 2. Two plant taxa, Lavandula angustifolia and Canna ‘sp.’, with differing floral morphology, were used to compare the value of DVR and direct observations in estimating honeybee (Apis mellifera) visitation, flower density and number of flowers visited per foraging bout. 3. The two methods yielded identical results when observing the structurally simple L. angustifolia at both high (10.54 ± 0.52 per plant) and low honeybee density (2.24 ± 0.20 per plant). However, DVR underestimated the number of flowers scored in the field of view (28.7 ± 1.8 direct vs. 22.7 ± 0.9 DVR), the number of honeybees observed (5.3 ± 0.8 direct vs. 3.7 ± 0.7 DVR) and the number of flowers visited during foraging bouts (8.3 ± 1.2 direct vs. 5.5 ± 1.0 DVR) on the more complex Canna ‘sp.’ 4. It is concluded that portable weatherproof DVR devices such as the GoPro Hero are valuable tools for pollination biologists, allowing a single researcher to make simultaneous observations of multiple plants in one or more sites, whilst also allowing the footage to be reviewed. However, DVR devices are limited by their depth and field of view when target plants are large or structurally complex.     

Migration and spawning energetics of the anadromous sea lamprey,Petromyzon marinus

Synopsis Energy expended in migration and reproduction was determined from measurements of caloric concentration and body and gonodal weight for nontrophic sea lampreys collected from different sites along the St. John River, New Brunswick. The estimated cost of locomotion in swimming the 140 km which separates the estuary from the spawning redds was 300 and 260 kcal for males and females respectively. Acutal distance which lampreys swam as well as mean swimming speed were estimated from a linear regression equation relating energy expenditure for locomotion and body weight. Energy expenditure for breeding was considerably greater than that catabolized throughout the upstream migration.