Membrane remodelling by a lipidated endosomal sorting complex required for transport-III chimera, in vitro.

The complexity of eukaryotic cells is underscored by the compartmentalization of chemical signals by phospholipid membranes. A grand challenge of synthetic biology is building life from the 'bottom-up', for the purpose of generating systems simple enough to precisely interrogate biological pathways or for adapting biology to perform entirely novel functions. Achieving compartmentalization of chemistries in an addressable manner is a task exquisitely refined by nature and embodied in a unique membrane remodelling machinery that pushes membranes away from the cytosol, the ESCRT-III (endosomal sorting complex required for transport-III) complex. Here, we show efforts to engineer a single ESCRT-III protein merging functional features from its different components. The activity of such a designed ESCRT-III is shown by its ability to drive the formation of compartments encapsulating fluorescent cargo. It appears that the modular nature of ESCRT-III allows its functional repurposing into a minimal machinery that performs sophisticated membrane remodelling, therefore enabling its use to create eukaryotic-like multi-compartment architectures.

Lipid organization and the morphology of solid-like domains in phase-separating binary lipid membranes.

In multi-component lipid membranes, phase separation can lead to the formation of domains. The morphology of fluid-like domains has been rationalized in terms of membrane elasticity and line tension. We show that the morphology of solid-like domains is governed by different physics, and instead reflects the molecular ordering of the lipids. An understanding of this link opens new possibilities for the rational design of patterned membranes.

Peptide:glycosaminoglycan hybrid hydrogels as an injectable intervention for spinal disc degeneration.

Degeneration of the spinal discs is a major cause of back pain. During the degeneration process, there is a loss of glycosaminoglycans (GAGs) from the proteoglycan-rich gel in the disc's nucleus, which adversely alters biomechanical performance. Current surgical treatments for back pain are highly invasive and have low success rates; there is an urgent need for minimally-invasive approaches that restore the physiological mechanics of the spine. Here we present an injectable peptide:GAG hydrogel that rapidly self-assembles in situ and restores the mechanics of denucleated intervertebral discs. It forms a gel with comparable mechanical properties to the native tissue within seconds to minutes depending on the peptide chosen. Unlike other biomaterials that have been proposed for this purpose, these hybrid hydrogels can be injected through a very narrow 25 G gauge needle, minimising damage to the surrounding soft tissue, and they mimic the ability of the natural tissue to draw in water by incorporating GAGs. Furthermore, the GAGs enhance the gelation kinetics and thermodynamic stability of peptide hydrogels, significantly reducing effusion of injected material from the intervertebral disc (GAG leakage of 8 ± 3% after 24 h when peptide present, compared to 39 ± 3% when no peptide present). In an ex vivo model, we demonstrate that the hydrogels can restore the compressive stiffness of denucleated bovine intervertebral discs. Compellingly, this novel biomaterial has the potential to transform the clinical treatment of back pain by resolving current surgical challenges, thus improving patient quality of life.

First Report of Flag Smut of Wheat Caused by Urocystis agropyri in the United Kingdom.

An isolated occurrence of flag smut of wheat, caused by Urocystis agropyri (G. Preuss) J. Schröt., was confirmed in the county of Essex, UK, in autumn-sown winter wheat (Triticum aestivum L.) cv. Riband grown from certified seed. The origin of the infection is unknown. Symptoms were first observed on 22 May 1998. The presence of U. agropyri was confirmed on the basis of the macroscopic symptoms on the host and the morphology of the pathogen (2). Long gray-black streaks parallel with the veins were observed on leaf blades, especially the flag leaf, and on leaf sheaths. The streaks consisted of lines of fungal sori developing between the leaf veins, giving a striped appearance. Eruption of the sori through the epidermis of the leaves had caused them to fray, exposing dark brown to black powdery spore masses. Microscopic examination revealed spore balls measuring 20 to 28 µm in diameter containing 1 to 3 spores per ball. Spores were dark brown measuring 12 to 17.5 µm in diameter and were surrounded by light brown sterile cells measuring 7 to 7.5 µm. Affected plants were stunted to about half the height of healthy plants. Some affected plants tillered excessively and in some cases the ear failed to emerge from the boot. Some diseased leaves were twisted and, where the host epidermis had ruptured to expose the spore masses, the affected parts had the appearance of being covered in black soot. All of the symptoms are typical of flag smut on wheat. Flag smut has been observed on grasses in every continent except Antartica. However, the distribution of the pathogen on wheat is more limited. Flag smut of wheat is known to occur in at least some of the countries of the European Union as well as (e.g.) the USA and Australia. This finding is significant because it had been considered that U. agropyri on wheat had reached the limits of its ecoclimatic zone, since it requires specific environmental conditions for infection and disease development, particularly a mild winter and an arid summer (1). The climatic conditions in Essex between September 1997 when the affected crop was planted and May 1998 when symptoms were first observed were considerably drier and warmer than normal, thus favoring the pathogen. This is the first report of U. agropyri on wheat in the UK. References: (1) R. F. Line. 1998. Pages 49-60 in: Bunts and Smuts of Wheat: An International Symposium. No. Am. Plant Prot. Org., Ottawa. (2) J. E. M. Mordue and J. M. Waller. 1981. Urocystis agropyri. CMI Descriptions of Pathogenic Fungi and Bacteria, No. 716. Kew, England.