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Abstract: Membrane proteins are essential components of many biochemical processes and are important pharmaceutical targets. Membrane protein structural biology provides the molecular rationale for these biochemical process as well as being a highly useful tool for drug discovery. Unfortunately, membrane protein structural biology is a difficult area of study due to low protein yields and high levels of instability especially when membrane proteins are removed from their native environments. Despite this instability, membrane protein structural biology has made great leaps over the last fifteen years. Today, the landscape is almost unrecognisable. The numbers of available atomic resolution structures have increased 10-fold though advances in crystallography and more recently by cryo-electron microscopy. These advances in structural biology were achieved through the efforts of many researchers around the world as well as initiatives such as the Membrane Protein Laboratory (MPL) at Diamond Light Source. The MPL has helped, provided access to and contributed to advances in protein production, sample preparation and data collection. Together, these advances have enabled higher resolution structures, from less material, at a greater rate, from a more diverse range of membrane protein targets. Despite this success, significant challenges remain. Here, we review the progress made and highlight current and future challenges that will be overcome.

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Abstract: A major limit of electric vehicle performance is the energy density of available mobile energy storage systems. Lithium ion (Li-ion) batteries are now well-known and have enabled many portable electronics as well as electronic vehicles. However, for greater market penetration and range competitiveness, a battery with greater practical energy density must be designed. This dissertation focuses on three methods of improving energy density in lithium based batteries: lithium oxygen (Li-O2) batteries, Li-rich cathodes for Li-ion batteries, and high voltage operation of simple transition metal oxide cathodes for Li-ion batteries. To evaluate each of these technologies, the reactivity of each system is monitored. Li-O2 batteries, a “beyond Li-ion" battery technology, have a very high theoretical energy density that is difficult to realize. After initial excitement surrounding the novel chemistry, many challenges associated with Li-O2 batteries have been highlighted in the past decade. Among these challenges, the reactivity of oxygen in the system is one of the most pressing. In this dissertation, the possible stability of LiO2, an advantageous discharge product to the typical Li2O2, is examined alongside binder degradation in the system. As the workings of a Li-ion battery require the removal and intercalation of Li, the theoretical capacity is determined by the amount of Li available for extraction from the cathode. Consequently, a method of increasing energy density in Li-ion batteries is to increase the stoichiometric ratio of Li in the cathode material. These "Li-rich" cathode materials demonstrate large capacities, but must compensate the additional Li with cation double redox or anion redox. The electrochemical cells must be operated to > 4.5 V vs Li/Li+ to reach these additional capacities, and this operation results in greater reactivity and instabilities. This dissertation examines the trends of high voltage instability, especially as it relates to oxygen redox, in these Li-rich cathode materials. Typical Li-ion batteries utilize only a fraction of the theoretical capacity available, only extracting around half of the available lithium from the layered transition metal oxide cathode material during charge. This is due to enhanced degradation mechanisms and reduced cyclability when additional Li is extracted at the necessitated higher voltages. Enabling operation of layered transition metal oxides at high voltages would result in increased capacity without the need for “beyond Li-ion" technologies. But first, the instabilities associated with Li extraction at voltages beyond the typical cut-off must be well-studied. Currently, the stability and degradation mechanisms of cathode materials even as common as LiCoO2 remain unclear. In studies presented in this dissertation, high voltage reactivity for layered transition metal oxide cathode materials is investigated. The main conclusions of the studies presented here are drawn from measurements monitoring the reactivity of each of the aforementioned technologies. Among the measurements presented in these studies, outgassing and gas evolution measurements by differential electrochemical mass spectrometry have proved paramount in utility. As cell reactivity and instability at high voltages is often accompanied by outgassing, these measurements have assisted in the elucidation of instability origins. Practical application of Li-O2 batteries remains elusive as additional instabilities are discovered, Li-rich cathode materials show promise as various methods of mitigating high voltage instabilities are discussed, and the major sources of high voltage reactivity of layered transition metal oxide cathode materials are evaluated here.

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Abstract: The molecular basis of antibody 5E5, which recognizes the entire GalNAc unit as a primary epitope is disclosed. The antibody's contacts with the peptide are limited to mostly two residues, allowing the antibody to show some degree of promiscuity. These findings open the door to the chemical design of peptide-mimetics for developing efficient anti-cancer vaccines and diagnostic tools.

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Abstract: Serratia marcescens is an opportunistic pathogen that commonly causes hospital-acquired infections and can utilize chitin-enriched nutrients as an alternative energy source. This study reports the identification of a chitoporin (ChiP), termed SmChiP, from the outer membrane of S. marcescens. Sequence alignment with genetically characterized ChiPs suggests that SmChiP is more closely related to the monomeric EcChiP from Escherichia coli than to the trimeric VhChiP from Vibrio campbellii. A single crystal of SmChiP grown under the condition 22%(w/v) PEG 8000, 0.1 M calcium acetate, 0.1 M MES pH 6.0 diffracted X-ray synchrotron radiation to 1.85 Å resolution. SmChiP co-crystallized with chitohexaose under the condition 19%(w/v) PEG 1500, 2 M ammonium phosphate monobasic, 0.1 M HEPES pH 7.0 diffracted X-rays to 2.70 Å resolution. Preliminary crystallographic analysis shows that both SmChiP crystal forms contain one molecule per asymmetric unit and that they belong to the tetragonal space groups P42212 and P41212, respectively. The SmChiP crystal has unit-cell parameters a = 82.97, b = 82.97, c = 189.53 Å, α = β = γ = 90°, while the crystal of SmChiP in complex with chitohexaose has unit-cell parameters a = 73.24, b = 73.24, c = 213.46 Å, α = β = γ = 90°. Initial assessment of the complex structure clearly revealed electron density for the sugar ligand. Structure determination of SmChiP in the absence and presence of chitohexaose should reveal the molecular basis of chitin utilization by S. marcescens.

Open Access

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Abstract: We report on the detection of primordial organic matter within the carbonaceous chondrite Maribo that is distinct from the majority of organics found in extraterrestrial samples. We have applied high-spatial resolution techniques to obtain C-N isotopic compositions, chemical, and structural information of this material. The organic matter is depleted in 15N relative to the terrestrial value at around δ15N ~ -200‰, close to compositions in the local interstellar medium. Morphological investigations by electron microscopy revealed that the material consists of µm- to sub-µm-sized diffuse particles dispersed within the meteorite matrix. Electron energy loss and synchrotron X-ray absorption near-edge structure spectroscopies show that the carbon functional chemistry is dominated by aromatic and C=O bonding environments similar to primordial organics from other carbonaceous chondrites. The nitrogen functional chemistry is characterized by C-N double and triple bonding environments distinct from what is usually found in 15N-enriched organics from aqueously altered carbonaceous chondrites. Our investigations demonstrate that Maribo represents one of the least altered CM chondrite breccias found to date and contains primordial organic matter, probably originating in the interstellar medium.