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Biology subjects

Barrow, D.

Publications and source records attributed to Barrow, D..

4 recordsLinked to original sources

Bayesian phylodynamic inference of population dynamics with dormancy

Many organisms employ reversible dormancy, or seedbank, in response to environmental fluctuations. This life-history strategy alters fundamental eco-evolutionary forces, leading to distinct patterns of genetic diversity. Two models of dormancy have been proposed based on the average duration of dormancy relative to coalescent timescales: weak seedbank, induced by scheduled seasonality (e.g., plants, invertebrates), and strong seedbank, where individuals stochastically switch between active and dormant states (e.g., bacteria, fungi). The weak seedbank coalescent is statistically equivalent to the Kingman coalescent with a scaled mutation rate, allowing the use of existing inference methods. In contrast, the strong seedbank coalescent differs fundamentally, as only active lineages can coalesce, while dormant lineages cannot. Additionally, dormant individuals typically mutate at a slower rate than active ones. Consequently, despite the significant role of dormancy in the eco-evolutionary dynamics of many organisms, no methods currently exist for inferring population dynamics involving dormancy and associated parameters. We present a Bayesian framework for jointly inferring a latent genealogy, seedbank parameters, and evolutionary parameters from molecular sequence data under the strong seedbank coalescent. We derive the exact probability density of genealogies sampled under the strong seedbank coalescent, characterize the corresponding likelihood function, and present efficient computational algorithms for its evaluation based on our theoretical framework. We develop a tailored Markov chain Monte Carlo sampler and implement our inference framework as a package SeedbankTree within BEAST2. Our work provides both a theoretical foundation and practical inference framework for studying the population genetic and genealogical impacts of dormancy.

evolutionary biology↗

3D-printing fabrication of microwave-microfluidic device for droplets network formation and characterisation

Microwave-microfluidic devices (MMDs) have emerged as precision tools for the rapid, accurate, sensitive, and non-invasive characterisation of low-volume liquids. However, the fabrication of MMDs remains a significant challenge due to the complexities associated with integrating fluidic ducts and electronic components. Herein, we present a versatile and economical 3D-printing approach for MMD fabrication, using liquid metal as an electrical conductor. Cyclic olefin copolymer, polylactic acid and polypropylene were identified as potential printable dielectric materials for MMD fabrication. 3D-printed cyclic olefin copolymer substrates exhibited the lowest loss tangent of 0.002 at 2.7GHz, making it an ideal material for high frequency engineering. Liquid metal, specifically gallium indium eutectic, was injected into the printed ducts to form conductive microwave structures. Exemplar MMDs were fabricated to integrate split-ring type microwave resonators and droplet-forming fluidic junctions. These devices were applied in the formation and characterisation of water-in-oil emulsions for constructing definable lipid-segregated droplet interface bilayer (DIB) networks. This work not only indicates the feasibility of using 3D-printing for rapid prototyping of customised MMDs but also demonstrates the potential of MMDs as a new research tool for biochemistry and synthetic biology.

bioengineering↗

Manipulation of encapsulated artificial phospholipid membranes using sub-micellar lysolipid concentrations.

Droplet Interface Bilayers (DIBs) constitute a commonly used model of artificial membranes for molecular biology studies with applications in synthetic biology research. However, these model membranes have limited accessibility due to their requirement to be surrounded by an oil environment. Here, we demonstrate in-situ bilayer manipulation of submillimeter, free-standing, encapsulated droplet interface bilayers (eDIBs) in hydrogel capsules formed using dual-material, 3D-printed microfluidic devices. These microfluidic devices required no post-fabrication assembly, nor surface treatment to achieve the high-order emulsification, required for the formation of robust eDIBs. The eDIB capsules were exposed to various concentrations of lysophosphatidylcholine (LPC), in order to investigate the interaction of lysolipids with three-dimensional, encapsulated droplet bilayer networks. Micellar LPC concentrations trigger the bursting of the eDIB droplets, while at concentrations below the critical micelle concentration (CMC), the encapsulated aqueous inner droplet networks endure structural changes, precisely affecting the DIB contact angles and bilayer area. Manipulation of these enclosed, 3D-orchestrated membrane mimics facilitates the exploration of readily accessible compartmentalized artificial cellular machinery. Collectively, the multi-compartmentalized capsules and the lysolipid-mediated membrane modulation, introduce a chemical approach to control the properties and mechanics of artificial cellular membranes, toward responsive soft material developments.

synthetic biology↗

Building programmable multicompartment artificial cells incorporating remotely activated protein channels using microfluidics and acoustic levitation

Intracellular compartments are functional units that support the metabolic processes within living cells, through spatiotemporal regulation of chemical reactions and biological processes. Consequently, as a step forward in the bottom-up creation of artificial cells, building analogous intracellular architectures is essential for the expansion of cell-mimicking functionality. Herein, we report the development of a droplet laboratory platform to engineer customised complex emulsion droplets as a multicompartment artificial cell chassis, using multiphase microfluidics and acoustic levitation. Such levitated constructs provide free-standing, dynamic, definable droplet networks for the encapsulation and organisation of chemical species. Equally, they can be remotely operated with pneumatic, heating, and magnetic elements for post-processing, including the incorporation of membrane proteins; alpha-hemolysin; and large-conductance mechanosensitive channel (MscL) and their activation. The assembly of droplet networks is three-dimensionally patterned with fluidic inputs configurations determining droplet contents and connectivity. Whilst acoustic manipulation can be harnessed to reconfigure the droplet network in situ. In addition, a mechanosensitive channel, MscL, can be repeatedly activated and deactivated in the levitated artificial cell by the application of acoustic and magnetic fields to modulate membrane tension on demand. This offers possibilities beyond one-time chemically mediated activation to provide repeated, non-contact control of membrane protein function. Collectively, this will expand our capability to program and operate increasingly sophisticated artificial cells as life-like materials.

synthetic biology↗