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  • Journal article
    Blanco JM, Danckert NP, Liu Z, Martinez-Gili L, Mullish BH, McDonald JA, Lindsay M, Sengupta R, McHugh N, Abraham S, Marchesi Jet al., 2022,

    NEW LINKS BETWEEN PSORIATIC ARTHRITIS AND THE GUT MICROBIOME SUGGEST A STRONGER ROLE OF THE GUT-JOINT AXIS

    , GASTROENTEROLOGY, Vol: 162, Pages: S456-S457, ISSN: 0016-5085
  • Journal article
    Hamilton A, Rizzo R, Brod S, Ono M, Perretti M, Cooper D, D'Acquisto Fet al., 2022,

    The immunomodulatory effects of social isolation in mice are linked to temperature control

    , BRAIN BEHAVIOR AND IMMUNITY, Vol: 102, Pages: 179-194, ISSN: 0889-1591
  • Journal article
    Paizs P, Mullish BH, Alexander JL, Maneta-Stavrakaki S, Sani M, Ford L, Monaghan T, Kinross JM, McDonald JA, Kao DH, Marchesi J, Takats Zet al., 2022,

    INTESTINAL MICROBIOTA TRANSPLANT FOR RECURRENT CLOSTRIODIOIDES DIFFICILE INFECTION IS ASSOCIATED WITH RESTORATION OF MICROBIAL ARYLSULFATASES AND SULFATIDE DEGRADATION

    , GASTROENTEROLOGY, Vol: 162, Pages: S649-S649, ISSN: 0016-5085
  • Journal article
    Baselga A, Gomez-Rodriguez C, Araujo MB, Castro-Insua A, Arenas M, Posada D, Vogler APet al., 2022,

    Joint analysis of species and genetic variation to quantify the role of dispersal and environmental constraints in community turnover

    , Ecography: pattern and diversity in ecology, Vol: 2022, Pages: 1-13, ISSN: 0906-7590

    Spatial turnover of biological communities is determined by both dispersal and environmental constraints. However, we lack quantitative predictions about how these factors interact and influence turnover across genealogical scales. In this study, we have implemented a predictive framework based on approximate Bayesian computation (ABC) to quantify the signature of dispersal and environmental constraints in community turnover. First, we simulated the distribution of haplotypes, intra-specific lineages and species in biological communities under different strengths of dispersal and environmental constraints. Our simulations show that spatial turnover rate is invariant across genealogical scales when dispersal limitation determines the species ranges. However, when environmental constraint limits species ranges, spatial turnover rates vary across genealogical scales. These simulations were used in an ABC framework to quantify the role of dispersal and environmental constraints in 16 empirical biological communities sampled from local to continental scales, including several groups of insects (both aquatic and terrestrial), molluscs and bats. In seven datasets, the observed genealogical invariance of spatial turnover, assessed with distance–decay curves, suggests a dispersal-limited scenario. In the remaining datasets, the variance in distance–decay curves across genealogical scales was best explained by various combinations of dispersal and environmental constraints. Our study illustrates how modelling spatial turnover at multiple genealogical scales (species and intraspecific lineages) provides relevant insights into the relative role of dispersal and environmental constraints in community turnover.

  • Journal article
    Vickaryous M, Williams C, Willan G, Kirby A, Herrel A, Kever L, Moazen M, Marghoub A, Rai S, Abzhanov A, Evans Set al., 2022,

    Histological Diversity And Evolution Of Lizard Osteoderms.

    , FASEB J, Vol: 36 Suppl 1

    Many reptiles reinforce the dermis with discrete mineralized organs known as osteoderms. Among lizards, osteoderms demonstrate species-specific differences in size, shape, and distribution across the body. Whether osteoderms also vary in details of tissue composition, including the organization of the fibrillar matrix, remains unclear. Here, we investigate osteoderm histology in three species-rich lizard groups: gekkotans (geckos), scincids (skinks), and anguimorphans (anguids, helodermatids, and related taxa). With one possible exception, all lizard osteoderms are dominated by bone tissue. Unexpectedly, representative members of all the major groups develop an enigmatic, collagen-poor capping tissue. Gekkotan osteoderms are rare (<2% of species) and demonstrate considerable histological heterogeneity between species. This includes variation in bone matrices, and the development of additional (non-osseous) skeletal tissues. In the gecko genus Geckolepis, putative osteoderms appear to lack bone and instead are composed of dense collagen plates capped by a vitreous collagen-poor tissue. Unlike geckos, osteoderms are common to virtually all skinks. Most skink osteoderms are compound elements, composed of multiple conjoined smaller plates (referred to as osteodermites). Histologically, skink osteoderms are dominated by lamellar bone with well-organized Sharpey's fibres linking adjacent plates together and some woven and parallel-fibred bone. Most species develop the collagen-poor capping tissue, particularly where adjacent osteodermites articulate with one another. Osteoderms are also common to many anguimorphans, but the histology varies considerably between taxa. While anguid and helodermatid osteoderms demonstrate multiple bone matrices (woven-fibred, parallel-fibred, lamellar bone, and Sharpey-fibred), Shinisaurus osteoderms are primarily woven-fibred and Sharpey-fibred bone, and those of Varanus are mostly parallel-fibred bone. Expression of the capping tissue a

  • Journal article
    Allgower F, Gamiz-Hernandez AP, Rutherford AW, Kaila VRIet al., 2022,

    Molecular Principles of Redox-Coupled Protonation Dynamics in Photosystem II

    , JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 144, Pages: 7171-7180, ISSN: 0002-7863
  • Journal article
    Rahman MM, Burian A, Creedy TJ, Vogler APet al., 2022,

    DNA-based assessment of environmental degradation in an unknown fauna: The freshwater macroinvertebrates of the Indo-Burmese hotspot

    , JOURNAL OF APPLIED ECOLOGY, Vol: 59, Pages: 1644-1658, ISSN: 0021-8901
  • Journal article
    Ortega D, Beeby M, 2022,

    How did the archaellum get its rotation?

    , Frontiers in Microbiology, Vol: 12, Pages: 1-6, ISSN: 1664-302X

    How changes in function evolve fascinates many evolutionary biologists. Particularly captivating is the evolution of rotation in molecular machines, as it evokes familiar machines that we have made ourselves. The archaellum, an archaeal analog of the bacterial flagellum, is one of the simplest rotary motors. It features a long helical propeller attached to a cell envelope-embedded rotary motor. Satisfyingly, the archaellum is one of many members of the large type IV filament superfamily, which includes pili, secretion systems, and adhesins, relationships that promise clues as to how the rotating archaellum evolved from a non-rotary ancestor. Nevertheless,determining exactly how the archaellum got its rotation remains frustratingly elusive. Here we review what is known about how the archaellum got its rotation, what clues exist, and what more is needed to address this question.

  • Journal article
    Racovita A, Prakash S, Varela C, Walsh M, Galizi R, Isalan M, Jaramillo Aet al., 2022,

    Engineered gene circuits capable of reinforcement learning allow bacteria to master gameplaying

    <jats:title>Abstract</jats:title><jats:p>The engineering of living cells able to learn by themselves algorithms such as playing board games —a classic challenge for artificial intelligence— will allow complex ecosystems and tissues to be chemically reprogrammed to learn complex decisions. However, current engineered gene circuits encoding decision-making algorithms have failed to implement self-programmability and they require supervised tuning. We show a strategy for engineering gene circuits to rewire themselves by reinforcement learning. We created a scalable general-purpose library of <jats:italic>Escherichia coli</jats:italic> strains encoding elementary adaptive genetic systems capable of persistently adjusting their relative levels of expression according to their previous behavior. Our strains can learn the mastery of 3x3 board games such as tic-tac-toe from a <jats:italic>tabula rasa</jats:italic> state of complete ignorance. We provide a general genetic mechanism for the autonomous learning of decisions in changeable environments.</jats:p><jats:sec><jats:title>One-Sentence Summary</jats:title><jats:p>We propose a scalable strategy to engineer gene circuits capable of autonomously learning decision-making in complex environments.</jats:p></jats:sec>

  • Journal article
    Weeks BC, O'Brien BK, Chu JJ, Claramunt S, Sheard C, Tobias JAet al., 2022,

    Morphological adaptations linked to flight efficiency and aerial lifestyle determine natal dispersal distance in birds

    , FUNCTIONAL ECOLOGY, Vol: 36, Pages: 1681-1689, ISSN: 0269-8463
  • Journal article
    Alif Ž, Dunning J, Chik HYJ, Burke T, Schroeder Jet al., 2022,

    What is the best fitness measure in wild populations? A case study on the power of short-term fitness proxies to predict reproductive value

    , PLoS One, Vol: 17, ISSN: 1932-6203

    Fitness is at the core of evolutionary theory, but it is difficult to measure accurately. One way to measure long-term fitness is by calculating the individual's reproductive value, which represents the expected number of allele copies an individual passes on to distant future generations. However, this metric of fitness is scarcely used because the estimation of individual's reproductive value requires long-term pedigree data, which is rarely available in wild populations where following individuals from birth to death is often impossible. Wild study systems therefore use short-term fitness metrics as proxies, such as the number of offspring produced. This study compared two frequently used short-term metrics for fitness obtained at different offspring life stages (eggs, hatchlings, fledglings and recruits), and compared their ability to predict reproductive values derived from the genetic pedigree of a wild passerine bird population. We used twenty years of precise field observations and a near-complete genetic pedigree to calculate reproductive success, individual growth rate and de-lifed fitness as lifetime fitness measures, and as annual de-lifed fitness. We compared the power of these metrics to predict reproductive values and lineage survival to the end of the study period. The three short-term fitness proxies predict the reproductive values and lineage survival only when measured at the recruit stage. There were no significant differences between the different fitness proxies at the same offspring stages in predicting the reproductive values and lineage survival. Annual fitness at one year old predicted reproductive values equally well as lifetime de-lifed fitness. However, none of the short-term fitness proxies were strongly associated with the reproductive values. The commonly used short-term fitness proxies best predict long-term fitness when measured at recruitment stage. Thus, because lifetime fitness measured at recruit stage and annual fitness in the

  • Journal article
    Kechagias K, Giannos P, Triantafyllidis KK, Falagas MEet al., 2022,

    Spotlight on early COVID-19 research productivity: a 1-year bibliometric analysis

    , Frontiers in Public Health, ISSN: 2296-2565

    Coronavirus disease 2019 (COVID-19), one of the most serious public health crises in over a century, has led to an unprecedented surge of publications across all areas of knowledge. The current study assessed the early research productivity on COVID-19 in terms of vaccination, diagnosis, treatment, symptoms, risk factors, nutrition and economy. The Scopus database was searched between January 1, 2020and December 31, 2020 to initially examine the research productivity on COVID-19, as measured by total publications by the 20 highest ranked countries according to gross domestic product. The literature search was then refined, and research productivity was assessed across seven major research domains related to COVID-19: vaccination, diagnosis, treatment, symptoms, risk factors, nutrition and economy. The initial literature search yielded 53,348 publications. Among these, 27,801 publications involved authorship from a single country and 22,119 publications involved authorship from multiple countries. Overall, the United States was the most productive country (n=13,491), with one and a half times or more publications than any other country, on COVID-19 and the selected domains related to it. However, following adjustment for population size, gross domestic product, and expenditure for research and development, countries of emerging economies such as India along countries of lower population density such as Switzerland, Indonesia and Turkey exhibited higher research productivity. The surge of COVID-19 publications in such short period of time underlines the capacity of the scientific community to respond against a global health emergency, however this may jeopardise research quality.

  • Journal article
    Tica J, Davenport B, Isalan M, 2022,

    Reducing metabolic burden in the PACEmid evolver system by remastering high copy phagemid vectors

    , Engineering Biology, ISSN: 2398-6182

    Orthogonal or non-cross-reacting transcription factors are used in synthetic biology as componentsof genetic circuits. Brödel et al. (2016) engineered 12 such cIλ transcription factor variants, using adirected evolution ‘PACEmid’ system. The variants operate as dual activator/repressors and expandgene circuit construction possibilities. However, the high-copy phagemid vectors carrying the cIλvariants imposed high metabolic burden upon cells. Here, we ‘remaster’ the phagemid backbones torelieve their burden substantially, exhibited by a recovery in E. coli growth. The remasteredphagemids’ ability to function within the PACEmid evolver system is maintained, as is the cIλtranscription factors’ activity within these vectors. The low-burden phagemid versions are moresuitable for use in PACEmid experiments and synthetic gene circuits; we have therefore replaced theoriginal high-burden phagemids on the Addgene repository. Our work emphasises the importance ofunderstanding metabolic burden and incorporating it into design steps in future synthetic biologyventures.

  • Journal article
    Budzak J, Rudenko G, 2022,

    Pedal to the metal: nuclear splicing bodies turbo-charge VSG mRNA production in African trypanosomes

    , Frontiers in Cell and Developmental Biology, Vol: 10, ISSN: 2296-634X

    The African trypanosome Trypanosoma brucei is a parasite of the mammalian bloodstream and tissues, where an antigenically variable Variant Surface Glycoprotein (VSG) coat protects it from immune attack. This dense layer comprised of ∼107 VSG proteins, makes VSG by far the most abundant mRNA (7–10% total) and protein (∼10% total) in the bloodstream form trypanosome. How can such prodigious amounts of VSG be produced from a single VSG gene? Extremely high levels of RNA polymerase I (Pol I) transcription of the active VSG provide part of the explanation. However, recent discoveries highlight the role of pre-mRNA processing, both in maintaining high levels of VSG transcription, as well as its monoallelic expression. Trypanosome mRNAs are matured through trans-splicing a spliced leader (SL) RNA to the 5’ end of precursor transcripts, meaning abundant SL RNA is required throughout the nucleus. However, requirement for SL RNA in the vicinity of the active VSG gene is so intense, that the cell reconfigures its chromatin architecture to facilitate interaction between the SL RNA genes and the active VSG. This presumably ensures that sufficient localised SL RNA is available, and not limiting for VSG mRNA expression. Recently, novel nuclear splicing bodies which appear to provide essential trans-splicing components, have been identified associating with the active VSG. These observations highlight the underappreciated role of pre-mRNA processing in modulating gene expression in trypanosomes. Dissecting the function of these nuclear RNA processing bodies should help us elucidate the mechanisms of both VSG expression and monoallelic exclusion in T. brucei.

  • Journal article
    Kordas RL, Pawar S, Kontopoulos D-G, Woodward G, O'Gorman EJet al., 2022,

    Metabolic plasticity can amplify ecosystem responses to global warming

    , NATURE COMMUNICATIONS, Vol: 13
  • Journal article
    Bian X, Garner B, Liu H, Vogler APet al., 2022,

    The SITE-100 project: site-based biodiversity genomics for species discovery, community ecology, and a global tree-of-life

    , Frontiers in Ecology and Evolution, Vol: 10, ISSN: 2296-701X

    Most insect communities are composed of evolutionary diverse lineages, but detailed phylogenetic analyses of whole communities are lacking, in particular in species-rich tropical faunas. Likewise, our knowledge of the Tree-of-Life to document life’s evolutionary diversity remains highly incomplete and especially requires the inclusion of unstudied lineages from species-rich ecosystems. Here we present the SITE-100 program, which is an attempt at building the Tree-of-Life from whole-community sampling of high-biodiversity sites around the globe. Combining the local data sets into a global tree produces an increasingly comprehensive tree, while also re-tracing evolutionary history of lineages constituting the local community. Local sets are collected in bulk in standardised passive traps and imaged with a large-scale high-resolution camera, which is followed by a parataxonomy step for the preliminary separation of morphospecies and selection of specimens for phylogenetic analysis. Selected specimens are used for individual DNA extraction and sequencing, usually to sequence mitochondrial genomes. All remaining specimens are bulk extracted and subjected to metabarcoding. Phylogenetic analysis on the mitogenomes produces a reference tree to which short barcode sequences are added in a secondary analysis using phylogenetic placement or backbone constrainedtree searches. However, the approach may be hampered by the fact that (1) mitogenomes are limited in phylogeneticinformativeness, and (2) site-based sampling may produce poor taxon coverage and cause a suite of challenges for phylogenetic inference. To mitigate problems of phylogenetic reconstruction at deep levels, we follow a hierarchical way of gathering molecular information, where nuclear genome and mitogenome data from taxonomically chosen specimens consolidate the base and middle portion of the tree, respectively, and adding species-resolution contributed by DNA barcode data. We posit that site-based samplin

  • Journal article
    Lee HJ, Ehsan M, Zhang X, Katsube S, Munk CF, Wang H, Ahmed W, Kumar A, Byrne B, Loland CJ, Guan L, Liu X, Chae PSet al., 2022,

    Development of 1,3-acetonedicarboxylate-derived glucoside amphiphiles (ACAs) for membrane protein study

    , CHEMICAL SCIENCE, Vol: 13, Pages: 5750-5759, ISSN: 2041-6520
  • Journal article
    Fu M, Zhang H, Yin M, Han Z, Bai Q, Peng Y, Shafik K, Zhai L, Hong N, Xu W, Wang G, Kotta-Loizou Iet al., 2022,

    A novel heptasegmented positive-sense single-stranded RNA virus from the phytopathogenic fungus colletotrichum fructicola

    , Journal of Virology, Vol: 96, Pages: 1-14, ISSN: 0022-538X

    In this study, a novel positive-sense single-stranded RNA (+ssRNA) mycovirus, tentatively named Colletotrichum fructicola RNA virus 1 (CfRV1), was identified in the phytopathogenic fungus Colletotrichum fructicola. CfRV1 has seven genomic components, encoding seven proteins from open reading frames (ORFs) flanked by highly conserved untranslated regions (UTRs). Proteins encoded by ORFs 1, 2, 3, 5, and 6 are more similar to the putative RNA-dependent RNA polymerase (RdRp), hypothetical protein (P2), methyltransferase, and two hypothetical proteins of Hadaka virus 1 (HadV1), a capsidless 10- or 11-segmented +ssRNA virus, while proteins encoded by ORFs 4 and 7 showed no detectable similarity to any known proteins. Notably, proteins encoded by ORFs 1 to 3 also share considerably high similarity with the corresponding proteins of polymycoviruses. Phylogenetic analysis conducted based on the amino acid sequence of CfRV1 RdRp and related viruses placed CfRV1 and HadV1 together in the same clade, close to polymycoviruses and astroviruses. CfRV1-infected C. fructicola strains demonstrate a moderately attenuated growth rate and virulence compared to uninfected isolates. CfRV1 is capsidless and potentially encapsulated in vesicles inside fungal cells, as revealed by transmission electron microscopy. CfRV1 and HadV1 are +ssRNA mycoviruses closely related to polymycoviruses and astroviruses, represent a new linkage between +ssRNA viruses and the intermediate double-stranded RNA (dsRNA) polymycoviruses, and expand our understanding of virus diversity, taxonomy, evolution, and biological traits. IMPORTANCE A scenario proposing that dsRNA viruses evolved from +ssRNA viruses is still considered controversial due to intergroup knowledge gaps in virus diversity. Recently, polymycoviruses and hadakaviruses were found as intermediate dsRNA and +ssRNA stages, respectively, between +ssRNA and dsRNA viruses. Here, we identified a novel +ssRNA mycovirus, Colletotrichum fructicola RNA virus

  • Journal article
    Dunn N, Savolainen V, Weber S, Andrzejaczek S, Carbone C, Curnick Det al., 2022,

    Elasmobranch diversity across a remote coral reef atoll revealed through environmental DNA metabarcoding

    , Zoological Journal of the Linnean Society, ISSN: 0024-4082

    As elasmobranchs are becoming increasingly threatened, efficient methods for monitoring the distribution and diversity of elasmobranch populations are required. Environmental DNA (eDNA) metabarcoding is an increasingly applied technique that enables mass identification of entire communities and is an effective method for the detection of rare and elusive species. We performed an eDNA metabarcoding survey for fish communities around a coral reef atoll in the Chagos Archipelago and assessed the diversity and distribution of elasmobranch species detected within these communities. Our eDNA survey detected 353 amplicon sequence variants (ASVs) attributed to fishes, 12 of which were elasmobranchs. There were no differences in fish communities based on the presence and absence of ASVs between sample depth (surface and 40m) or sampling habitat, but communities based on read abundance were significantly different between habitats. The dominant elasmobranch species were grey reef (Carcharhinus amblyrhynchos) and silvertip (C. albimarginatus) sharks, and elasmobranch communities were significantly different between sampling depth and habitat. Overall, we find that eDNA metabarcoding can be used to reveal the diversity of elasmobranchs within broader taxonomic assays, but further research and development of targeted metabarcoding primers may be required before it can be integrated into a toolkit for monitoring these species.

  • Journal article
    Fernandez-Gonzalez A, Cowen S, Kim J, Foy CA, Jimenez J, Huggett JF, Whale ASet al., 2022,

    Applicability of control materials to support gene promoter characterization and expression in engineered cells using digital PCR

    , Analytical Chemistry, Vol: 94, Pages: 5566-5574, ISSN: 0003-2700

    The use of standardized components and processes in engineering underpins the design-build-test model, and the engineering of biological systems is no different. Substantial efforts to standardize both the components and the methods to validate the engineered biological systems is ongoing. This study has developed a panel of control materials encoding the commonly used reporter genes GFP and RFP as DNA or RNA molecules. Each panel contained up to six samples with increasingly small copy number differences between the two reporter genes that ranged from 1- to 2-fold differences. These copy number differences represent the magnitude of changes that may need to be measured to validate an engineered system. Using digital PCR (dPCR), we demonstrated that it is possible to quantify changes in both gene and gene transcript numbers both within and between samples down to 1.05-fold. We corroborated these findings using a simple gene circuit within a bacterial model to demonstrate that dPCR was able to precisely identify small changes in gene expression of two transcripts in response to promoter stimulation. Finally, we used our findings to highlight sources of error that can contributed to the measurement uncertainty in the measurement of small ratios in biological systems. Together, the development of a panel of control materials and validation of a high accuracy method for the measurement of small changes in gene expression, this study can contribute to the engineering biology “toolkit” of methods and materials to support the current standardization efforts.

  • Journal article
    McGreig J, Uri H, Antczak M, Michaelis M, Sternberg M, Wass Met al., 2022,

    3DLigandSite: Structure-based prediction of protein-ligand binding sites

    , Nucleic Acids Research, Vol: 50, Pages: W13-W1=20, ISSN: 0305-1048

    3DLigandSite is a web tool for the prediction of ligand-binding sites in proteins. Here, we report a significant update since the first release of 3DLigandSite in 2010. The overall methodology remains the same, with candidate binding sites in proteins inferred using known binding sites in related protein structures as templates. However, the initial structural modelling step now uses the newly available structures from the AlphaFold database or alternatively Phyre2 when AlphaFold structures are not available. Further, a sequence-based search using HHSearch has been introduced to identify template structures with bound ligands that are used to infer the ligand-binding residues in the query protein. Finally, we introduced a machine learning element as the final prediction step, which improves the accuracy of predictions and provides a confidence score for each residue predicted to be part of a binding site. Validation of 3DLigandSite on a set of 6416 binding sites obtained 92% recall at 75% precision for non-metal binding sites and 52% recall at 75% precision for metal binding sites. 3DLigandSite is available at https://www.wass-michaelislab.org/3dligandsite. Users submit either a protein sequence or structure. Results are displayed in multiple formats including an interactive Mol* molecular visualization of the protein and the predicted binding sites.

  • Journal article
    Makrydaki E, Donini R, Krueger A, Royle K, Moya-Ramirez I, Kuntz DA, Rose DR, Haslam SM, Polizzi K, Kontoravdi Cet al., 2022,

    Immobilised enzyme cascade for targeted glycosylation

    <jats:title>Abstract</jats:title><jats:p>Glycosylation is a critical post-translational modification of proteins, improving properties such as folding, half-life and functionality. However, glycosylation is a non-templated and heterogeneous process because of the promiscuity of the enzymes involved. Here we describe a platform for <jats:underline>s</jats:underline>eq<jats:underline>u</jats:underline>ential <jats:underline>g</jats:underline>lycosyl<jats:underline>a</jats:underline>tion <jats:underline>r</jats:underline>eactions for <jats:underline>ta</jats:underline>ilo<jats:underline>r</jats:underline>ed su<jats:underline>g</jats:underline>ar s<jats:underline>t</jats:underline>ructures (SUGAR-TARGET) that allows bespoke, controlled N-linked glycosylation <jats:italic>in vitro</jats:italic>. This novel proof-of-concept system is enabled by immobilised enzymes produced with a “one-step immobilisation/purification” method to express, biotinylate <jats:italic>in vivo</jats:italic> and immobilise glycosyltransferases. The immobilised enzymes are used in a reaction cascade mimicking a human-like N-linked glycosylation pathway where promiscuity naturally exists. The enzyme cascade is applied to free glycans, and a monomeric Fc domain expressed in glycoengineered <jats:italic>Pichia pastoris</jats:italic>, yielding near homogeneous glycoforms (&gt;95% conversion). Finally, immobilised β-1,4 galactosyltransferase is used to enhance the galactosylation profile of three different IgGs yielding 80.2 – 96.3 % terminal galactosylation. Enzyme recycling was further demonstrated for 7 cycles, with a combined reaction time greater than 140 hours. The novel SUGAR-TARGET platform is easy to implement, modular and reusable, and therefore can lead to the development of homogeneous glycan structures fo

  • Journal article
    Henson SA, Laufkotter C, Leung S, Giering SLC, Palevsky H, Cavan ELet al., 2022,

    Uncertain response of ocean biological carbon export in a changing world

    , NATURE GEOSCIENCE, Vol: 15, Pages: 248-254, ISSN: 1752-0894
  • Journal article
    Broto A, Gaspari E, Miravet-Verde S, Martins dos Santos VAP, Isalan Met al., 2022,

    A genetic toolkit and gene switches to limit Mycoplasma growth for biosafety applications

    , Nature Communications, Vol: 13, ISSN: 2041-1723

    Mycoplasmas have exceptionally streamlined genomes and are strongly adapted to their many hosts, which provide them with essential nutrients. Owing to their relative genomic simplicity, Mycoplasmas have been used to develop chassis for biotechnological applications. However, the dearth of robust and precise toolkits for genomic manipulation and tight regulation has hindered any substantial advance. Herein we describe the construction of a robust genetic toolkit for M. pneumoniae, and its successful deployment to engineer synthetic gene switches that control and limit Mycoplasma growth, for biosafety containment applications. We found these synthetic gene circuits to be stable and robust in the long-term, in the context of a minimal cell. With this work, we lay a foundation to develop viable and robust biosafety systems to exploit a synthetic Mycoplasma chassis for live attenuated vectors for therapeutic applications.

  • Journal article
    Viola S, Roseby W, Santabarabara S, Nürnberg D, Assunção R, Dau H, Sellés J, Boussac A, Fantuzzi A, Rutherford AWet al., 2022,

    Impact of energy limitations on function and resilience in long-wavelength Photosystem II

    <jats:title>Abstract</jats:title><jats:p>Photosystem II (PSII) uses the energy from red light to split water and reduce quinone, an energy-demanding process based on chlorophyll a (Chl-a) photochemistry. Two kinds of cyanobacterial PSII can use Chl-d and Chl-f to perform the same reactions using lower energy, far-red light. PSII from <jats:italic>Acaryochloris marina</jats:italic> has Chl-d replacing all but one of its 35 Chl-a, while PSII from <jats:italic>Chroococcidiopsis thermalis</jats:italic>, a facultative far-red species, has just 4 Chl-f and 1 Chl-d and 30 Chl-a. From bioenergetic considerations, the far-red PSII were predicted to lose photochemical efficiency and/or resilience to photodamage. Here, we compare enzyme turnover efficiency, forward electron transfer, back-reactions and photodamage in Chl-f-PSII, Chl-d-PSII and Chl-a-PSII. We show that: i) all types of PSII have a comparable efficiency in enzyme turnover; ii) the modified energy gaps on the acceptor side of Chl-d-PSII favor recombination via P<jats:sub>D1</jats:sub><jats:sup>+</jats:sup>Phe<jats:sup>-</jats:sup> repopulation, leading to increased singlet oxygen production and greater sensitivity to high-light damage compared to Chl-a-PSII and Chl-f-PSII; ii) the acceptor-side energy gaps in Chl-f-PSII are tuned to avoid harmful back reactions, favoring resilience to photodamage over efficiency of light usage. The results are explained by the differences in the redox tuning of the electron transfer cofactors Phe and Q<jats:sub>A</jats:sub> and in the number and layout of the chlorophylls that share the excitation energy with the primary electron donor. PSII has adapted to lower energy in two distinct ways, each appropriate for its specific environment but with different functional penalties.</jats:p>

  • Journal article
    Yi L, Liu B, Nixon PJ, Yu J, Chen Fet al., 2022,

    Recent advances in understanding the structural and functional evolution of FtsH proteases

    , Frontiers in Plant Science, Vol: 13, Pages: 1-16, ISSN: 1664-462X

    The FtsH family of proteases are membrane-anchored, ATP-dependent, zinc metalloproteases. They are universally present in prokaryotes and the mitochondria and chloroplasts of eukaryotic cells. Most bacteria bear a single ftsH gene that produces hexameric homocomplexes with diverse house-keeping roles. However, in mitochondria, chloroplasts and cyanobacteria, multiple FtsH homologues form homo and heterocomplexes with specialised functions in maintaining photosynthesis and respiration. The diversification of FtsH homologues combined with selective pairing of FtsH isomers is a versatile strategy to enable functional adaptation. In this article we summarise recent progress in understanding the evolution, structure and function of FtsH proteases with a focus on the role of FtsH in photosynthesis and respiration.

  • Journal article
    Cavender-Bares J, Nelson E, Meireles JE, Lasky J, Miteva DA, Nowak D, Pearse W, Helmus M, Zanne AE, Fagan W, otherset al., 2022,

    The hidden value of trees: quantifying the ecosystem services of tree lineages and their major threats across the continental US

    , PLoS
  • Journal article
    Ehsan M, Wang H, Katsube S, Munk CF, Du Y, Youn T, Yoon S, Byrne B, Loland CJ, Guan L, Kobilka BK, Chae PSet al., 2022,

    Glyco-Steroidal Amphiphiles (GSAs) for membrane protein structural study

    , ChemBioChem: a European journal of chemical biology, Vol: 23, Pages: 1-8, ISSN: 1439-4227

    Integral membrane proteins pose considerable challenges to high resolution structural analysis. Maintaining membrane proteins in their native state during protein isolation is essential for structural study of these bio-macromolecules. Detergents are the most commonly used amphiphilic compounds for stabilizing membrane proteins in solution outside a lipid bilayer. We previously introduced a glyco-diosgenin (GDN) detergent that was shown to be highly effective at stabilizing a wide range of membrane proteins. This steroidal detergent has additionally gained attention due to its compatibility with membrane protein structure study via cryo-EM. However, synthetic inconvenience limits widespread use of GDN in membrane protein study. To improve its synthetic accessibility and to further enhance detergent efficacy for protein stabilization, we designed a new class of glyco-steroid-based detergents using three steroid units: cholestanol, cholesterol and diosgenin. These new detergents were efficiently prepared and showed marked efficacy for protein stabilization in evaluation with a few model membrane proteins including two G protein-coupled receptors. Some new agents were not only superior to a gold standard detergent, DDM (n-dodecyl-β-d-maltoside), but were also more effective than the original GDN at preserving protein integrity long term. These agents represent valuable alternatives to GDN, and are likely to facilitate structural determination of challenging membrane proteins.

  • Journal article
    Giannos P, Triantafyllidis KK, Geropoulos G, Kechagias Ket al., 2022,

    Persistent hiccups as an atypical presentation of SARS-CoV-2 infection: a systematic review of case reports

    , Frontiers in Neurology, Vol: 13, ISSN: 1664-2295

    Symptoms such as fever, dry cough, dyspnoea, and respiratory distress are commonly described in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recently, a growing number of cases pertained to persistent hiccups have been reported by SARS-CoV-2 infected patients. The aim of this systematic review was to screen the current literature and provide a summary of the reported cases of SARS-CoV-2 infected patients presenting with persistent hiccups. The PubMed, Scoups and Web of Science databases were searched according to PRISMA guidelines from inception until 1, 2020 and December 31, 2020. Case reports or case series that provided a separate clinical description for patients with presenting complaints of persistent hiccups before or after COVID-19 diagnosis, were retrieved. The critical appraisal checklist for case reports provided by the Joanna Briggs Institute (JBI) was employed to evaluate the overall quality of the eligible studies. We identified 13 eligible studies that included 16 patients in which presenting complaints of hiccups were reported by hospitalised and emergency department-admitted COVID-19 patients. The mean duration of hiccups was 4.6 days reported in 87% (14/16) patients. Hypertension was the most common comorbidity present in 50% (8/16) of patients followed by diabetes mellitus (4/16). Moreover, 43% (7/16) of patients received only one medication for managing the hiccups with metoclopramide (5/16) followed by chlorpromazine and baclofen (4/16) used as primary treatment. Equally, 43% of patients (7/16) received dexamethasone followed by azithromycin (5/16), ivermectin (4/16) and ceftriaxone (4/16) for managing the infection from SARS-CoV-2. The majority of patients (14/16) improved after initiation of treatment. Persistent hiccups are possibly a rare symptom clinicians may expect to encounter in patients infected with SARS-CoV-2. Although there is not ample proof to propose causation, increased awareness about the

  • Journal article
    McClure C, Aughey G, Hassan A, Butt K, Estacio Gomez A, Duggal A, Ying Sia C, Barber A, Southall Tet al., 2022,

    An auxin-inducible, GAL4-compatible, gene expression system for Drosophila

    , eLife, Vol: 11, Pages: 1-18, ISSN: 2050-084X

    The ability to control transgene expression, both spatially and temporally, is essential for studying model organisms. In Drosophila, spatial control is primarily provided by the GAL4/UAS system, whilst temporal control relies on a temperature-sensitive GAL80 (which inhibits GAL4) and drug-inducible systems. However, these are not ideal. Shifting temperature can impact on many physiological and behavioural traits, and the current drug-inducible systems are either leaky, toxic, incompatible with existing GAL4-driver lines, or do not generate effective levels of expression. Here, we describe the auxin-inducible gene expression system (AGES). AGES relies on the auxin-dependent degradation of a ubiquitously expressed GAL80, and therefore, is compatible with existing GAL4-driver lines. Water-soluble auxin is added to fly food at a low, non-lethal, concentration, which induces expression comparable to uninhibited GAL4 expression. The system works in both larvae and adults, providing a stringent, non-lethal, cost-effective, and convenient method for temporally controlling GAL4 activity in Drosophila.

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