in Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Acute myeloid leukemia (AML) is a clonal disorder arising from hematopoietic myeloid progenitors. Aberrantly activated tyrosine kinases (TK) are involved in leukemogenesis and are associated with poor treatment outcome. Kinase inhibitor (KI) treatment has shown promise in improving patient outcome in AML. However, inhibitor selection for patients is suboptimal. In a preclinical effort to address KI selection, we analyzed a panel of 16 AML cell lines using phosphotyrosine (pY) enrichment-based, label-free phosphoproteomics. The Integrative Inferred Kinase Activity (INKA) algorithm was used to identify hyperphosphorylated, active kinases as candidates for KI treatment, and efficacy of selected KIs was tested. Heterogeneous signaling was observed with between 241 and 2764 phosphopeptides detected per cell line. Of 4853 identified phosphopeptides with 4229 phosphosites, 4459 phosphopeptides (4430 pY) were linked to 3605 class I sites (3525 pY). INKA analysis in single cell lines successfully pinpointed driver kinases (PDGFRA, JAK2, KIT and FLT3) corresponding with activating mutations present in these cell lines. Furthermore, potential receptor tyrosine kinase (RTK) drivers, undetected by standard molecular analyses, were identified in four cell lines (FGFR1 in KG-1 and KG-1a, PDGFRA in Kasumi-3, and FLT3 in MM6). These cell lines proved highly sensitive to specific KIs. Six AML cell lines without a clear RTK driver showed evidence of MAPK1/3 activation, indicative of the presence of activating upstream RAS mutations. Importantly, FLT3 phosphorylation was demonstrated in two clinical AML samples with a FLT3 internal tandem duplication (ITD) mutation. Our data show the potential of pY-phosphoproteomics and INKA analysis to provide insight in AML TK signaling and identify hyperactive kinases as potential targets for treatment in AML cell lines. These results warrant future investigation of clinical samples to further our understanding of TK phosphorylation in relation to clinical response in the individual patient. Full Article
in Identification of an Unconventional Subpeptidome Bound to the Behcet's Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Human leukocyte antigen (HLA) B*51:01 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly genetically associated with Behcet's disease (BD). Previous studies have defined two subgroups of HLA-B*51 peptidome containing proline (Pro) or alanine (Ala) at position 2 (P2). Little is known about the unconventional non-Pro/Ala2 HLA-B*51-bound peptides. We aimed to study the features of this novel subpeptidome, and investigate its regulation by ERAP1. CRISPR-Cas9 was used to generate an HLA-ABC-triple knockout HeLa cell line (HeLa.ABC-KO), which was subsequently transduced to express HLA-B*51:01 (HeLa.ABC-KO.B51). ERAP1 was silenced using lentiviral shRNA. Peptides bound to HLA-B*51:01 were eluted and analyzed by mass spectrometry. The characteristics of non-Pro/Ala2, Pro2, and Ala2 peptides and their alteration by ERAP1 silencing were investigated. Effects of ERAP1 silencing on cell surface expression of HLA-B*51:01 were studied using flow cytometry. More than 20% of peptides eluted from HLA-B*51:01 lacked Pro or Ala at P2. This unconventional group of HLA-B*51:01-bound peptides was relatively enriched for 8-mers (with relatively fewer 9-mers) compared with the Pro2 and Ala2 subpeptidomes and had similar N-terminal and C-terminal residue usages to Ala2 peptides (with the exception of the less abundant leucine at position ). Knockdown of ERAP1 increased the percentage of non-Pro/Ala2 from 20% to ~40%, increased the percentage of longer (10-mer and 11-mer) peptides eluted from HLA-B*51:01 complexes, and abrogated the predominance of leucine at P1. Interestingly knockdown of ERAP1 altered the length and N-terminal residue usage of non-Ala2&Pro2 and Ala2 but not the Pro2 peptides. Finally, ERAP1 silencing regulated the expression levels of cell surface HLA-B*51 in a cell-type-dependent manner. In conclusion, we have used a novel methodology to identify an unconventional but surprisingly abundant non-Pro/Ala2 HLA-B*51:01 subpeptidome. It is increased by knockdown of ERAP1, a gene affecting the risk of developing BD. This has implications for theories of disease pathogenesis. Full Article
in Quantitative Profiling of the Human Substantia Nigra Proteome from Laser-capture Microdissected FFPE Tissue [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Laser-capture microdissection (LCM) allows the visualization and isolation of morphologically distinct subpopulations of cells from heterogeneous tissue specimens. In combination with formalin-fixed and paraffin-embedded (FFPE) tissue it provides a powerful tool for retrospective and clinically relevant studies of tissue proteins in a healthy and diseased context. We first optimized the protocol for efficient LCM analysis of FFPE tissue specimens. The use of SDS containing extraction buffer in combination with the single-pot solid-phase-enhanced sample preparation (SP3) digest method gave the best results regarding protein yield and protein/peptide identifications. Microdissected FFPE human substantia nigra tissue samples (~3,000 cells) were then analyzed, using tandem mass tag (TMT) labeling and LC-MS/MS, resulting in the quantification of >5,600 protein groups. Nigral proteins were classified and analyzed by abundance, showing an enrichment of extracellular exosome and neuron-specific gene ontology (GO) terms among the higher abundance proteins. Comparison of microdissected samples with intact tissue sections, using a label-free shotgun approach, revealed an enrichment of neuronal cell type markers, such as tyrosine hydroxylase and alpha-synuclein, as well as proteins annotated with neuron-specific GO terms. Overall, this study provides a detailed protocol for laser-capture proteomics using FFPE tissue and demonstrates the efficiency of LCM analysis of distinct cell subpopulations for proteomic analysis using low sample amounts. Full Article
in An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100x) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ~2500 proteins and precise quantification of ~1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells. Full Article
in Human Hepatocyte Nuclear Factor 4-{alpha} Encodes Isoforms with Distinct Transcriptional Functions [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 HNF4α is a nuclear receptor produced as 12 isoforms from two promoters by alternative splicing. To characterize the transcriptional capacities of all 12 HNF4α isoforms, stable lines expressing each isoform were generated. The entire transcriptome associated with each isoform was analyzed as well as their respective interacting proteome. Major differences were noted in the transcriptional function of these isoforms. The α1 and α2 isoforms were the strongest regulators of gene expression whereas the α3 isoform exhibited significantly reduced activity. The α4, α5, and α6 isoforms, which use an alternative first exon, were characterized for the first time, and showed a greatly reduced transcriptional potential with an inability to recognize the consensus response element of HNF4α. Several transcription factors and coregulators were identified as potential specific partners for certain HNF4α isoforms. An analysis integrating the vast amount of omics data enabled the identification of transcriptional regulatory mechanisms specific to certain HNF4α isoforms, hence demonstrating the importance of considering all isoforms given their seemingly diverse functions. Full Article
in The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium. Full Article
in Decreased Immunoglobulin G Core Fucosylation, A Player in Antibody-dependent Cell-mediated Cytotoxicity, is Associated with Autoimmune Thyroid Diseases [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels. Full Article
in Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches [Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The study of protein subcellular distribution, their assembly into complexes and the set of proteins with which they interact with is essential to our understanding of fundamental biological processes. Complementary to traditional assays, proximity-dependent biotinylation (PDB) approaches coupled with mass spectrometry (such as BioID or APEX) have emerged as powerful techniques to study proximal protein interactions and the subcellular proteome in the context of living cells and organisms. Since their introduction in 2012, PDB approaches have been used in an increasing number of studies and the enzymes themselves have been subjected to intensive optimization. How these enzymes have been optimized and considerations for their use in proteomics experiments are important questions. Here, we review the structural diversity and mechanisms of the two main classes of PDB enzymes: the biotin protein ligases (BioID) and the peroxidases (APEX). We describe the engineering of these enzymes for PDB and review emerging applications, including the development of PDB for coincidence detection (split-PDB). Lastly, we briefly review enzyme selection and experimental design guidelines and reflect on the labeling chemistries and their implication for data interpretation. Full Article
in Profiling Cell Signaling Networks at Single-cell Resolution [Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Signaling networks process intra- and extracellular information to modulate the functions of a cell. Deregulation of signaling networks results in abnormal cellular physiological states and often drives diseases. Network responses to a stimulus or a drug treatment can be highly heterogeneous across cells in a tissue because of many sources of cellular genetic and non-genetic variance. Signaling network heterogeneity is the key to many biological processes, such as cell differentiation and drug resistance. Only recently, the emergence of multiplexed single-cell measurement technologies has made it possible to evaluate this heterogeneity. In this review, we categorize currently established single-cell signaling network profiling approaches by their methodology, coverage, and application, and we discuss the advantages and limitations of each type of technology. We also describe the available computational tools for network characterization using single-cell data and discuss potential confounding factors that need to be considered in single-cell signaling network analyses. Full Article
in A comprehensive evaluation of a typical plant telomeric G-quadruplex (G4) DNA reveals the dynamics of G4 formation, rearrangement, and unfolding [Plant Biology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4. Full Article
in Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015 [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms. Full Article
in Biochemical and structural insights into how amino acids regulate pyruvate kinase muscle isoform 2 [Enzymology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes. Full Article
in X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition. Full Article
in Structural basis of cell-surface signaling by a conserved sigma regulator in Gram-negative bacteria [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Cell-surface signaling (CSS) in Gram-negative bacteria involves highly conserved regulatory pathways that optimize gene expression by transducing extracellular environmental signals to the cytoplasm via inner-membrane sigma regulators. The molecular details of ferric siderophore-mediated activation of the iron import machinery through a sigma regulator are unclear. Here, we present the 1.56 Å resolution structure of the periplasmic complex of the C-terminal CSS domain (CCSSD) of PupR, the sigma regulator in the Pseudomonas capeferrum pseudobactin BN7/8 transport system, and the N-terminal signaling domain (NTSD) of PupB, an outer-membrane TonB-dependent transducer. The structure revealed that the CCSSD consists of two subdomains: a juxta-membrane subdomain, which has a novel all-β-fold, followed by a secretin/TonB, short N-terminal subdomain at the C terminus of the CCSSD, a previously unobserved topological arrangement of this domain. Using affinity pulldown assays, isothermal titration calorimetry, and thermal denaturation CD spectroscopy, we show that both subdomains are required for binding the NTSD with micromolar affinity and that NTSD binding improves CCSSD stability. Our findings prompt us to present a revised model of CSS wherein the CCSSD:NTSD complex forms prior to ferric-siderophore binding. Upon siderophore binding, conformational changes in the CCSSD enable regulated intramembrane proteolysis of the sigma regulator, ultimately resulting in transcriptional regulation. Full Article
in Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases. Full Article
in Biophysical characterization of SARAH domain-mediated multimerization of Hippo pathway complexes in Drosophila [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Hippo pathway signaling limits cell growth and proliferation and maintains the stem-cell niche. These cellular events result from the coordinated activity of a core kinase cassette that is regulated, in part, by interactions involving Hippo, Salvador, and dRassF. These interactions are mediated by a conserved coiled-coil domain, termed SARAH, in each of these proteins. SARAH domain–mediated homodimerization of Hippo kinase leads to autophosphorylation and activation. Paradoxically, SARAH domain–mediated heterodimerization between Hippo and Salvador enhances Hippo kinase activity in cells, whereas complex formation with dRassF inhibits it. To better understand the mechanism by which each complex distinctly modulates Hippo kinase and pathway activity, here we biophysically characterized the entire suite of SARAH domain–mediated complexes. We purified the three SARAH domains from Drosophila melanogaster and performed an unbiased pulldown assay to identify all possible interactions, revealing that isolated SARAH domains are sufficient to recapitulate the cellular assemblies and that Hippo is a universal binding partner. Additionally, we found that the Salvador SARAH domain homodimerizes and demonstrate that this interaction is conserved in Salvador's mammalian homolog. Using native MS, we show that each of these complexes is dimeric in solution. We also measured the stability of each SARAH domain complex, finding that despite similarities at both the sequence and structural levels, SARAH domain complexes differ in stability. The identity, stoichiometry, and stability of these interactions characterized here comprehensively reveal the nature of SARAH domain–mediated complex formation and provide mechanistic insights into how SARAH domain–mediated interactions influence Hippo pathway activity. Full Article
in Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc. Full Article
in Atomic force microscopy-based characterization of the interaction of PriA helicase with stalled DNA replication forks [DNA and Chromosomes] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB. Full Article
in Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections. Full Article
in Tracking isotopically labeled oxidants using boronate-based redox probes [Methods and Resources] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Reactive oxygen and nitrogen species have been implicated in many biological processes and diseases, including immune responses, cardiovascular dysfunction, neurodegeneration, and cancer. These chemical species are short-lived in biological settings, and detecting them in these conditions and diseases requires the use of molecular probes that form stable, easily detectable, products. The chemical mechanisms and limitations of many of the currently used probes are not well-understood, hampering their effective applications. Boronates have emerged as a class of probes for the detection of nucleophilic two-electron oxidants. Here, we report the results of an oxygen-18–labeling MS study to identify the origin of oxygen atoms in the oxidation products of phenylboronate targeted to mitochondria. We demonstrate that boronate oxidation by hydrogen peroxide, peroxymonocarbonate, hypochlorite, or peroxynitrite involves the incorporation of oxygen atoms from these oxidants. We therefore conclude that boronates can be used as probes to track isotopically labeled oxidants. This suggests that the detection of specific products formed from these redox probes could enable precise identification of oxidants formed in biological systems. We discuss the implications of these results for understanding the mechanism of conversion of the boronate-based redox probes to oxidant-specific products. Full Article
in Templated folding of intrinsically disordered proteins [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Much of our current knowledge of biological chemistry is founded in the structure-function relationship, whereby sequence determines structure that determines function. Thus, the discovery that a large fraction of the proteome is intrinsically disordered, while being functional, has revolutionized our understanding of proteins and raised new and interesting questions. Many intrinsically disordered proteins (IDPs) have been determined to undergo a disorder-to-order transition when recognizing their physiological partners, suggesting that their mechanisms of folding are intrinsically different from those observed in globular proteins. However, IDPs also follow some of the classic paradigms established for globular proteins, pointing to important similarities in their behavior. In this review, we compare and contrast the folding mechanisms of globular proteins with the emerging features of binding-induced folding of intrinsically disordered proteins. Specifically, whereas disorder-to-order transitions of intrinsically disordered proteins appear to follow rules of globular protein folding, such as the cooperative nature of the reaction, their folding pathways are remarkably more malleable, due to the heterogeneous nature of their folding nuclei, as probed by analysis of linear free-energy relationship plots. These insights have led to a new model for the disorder-to-order transition in IDPs termed “templated folding,” whereby the binding partner dictates distinct structural transitions en route to product, while ensuring a cooperative folding. Full Article
in Crystallographic and kinetic analyses of the FdsBG subcomplex of the cytosolic formate dehydrogenase FdsABG from Cupriavidus necator [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD+-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium Cupriavidus necator H16 both with and without bound NADH. The structures revealed that the two iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG, are closer to the FMN than they are in other NADH dehydrogenases. Rapid kinetic studies and EPR measurements of rapid freeze-quenched samples of the NADH reduction of FdsBG identified a neutral flavin semiquinone, FMNH•, not previously observed to participate in NADH-mediated reduction of the FdsABG holoenzyme. We found that this semiquinone forms through the transfer of one electron from the fully reduced FMNH−, initially formed via NADH-mediated reduction, to the Fe2S2 cluster. This Fe2S2 cluster is not part of the on-path chain of iron-sulfur clusters connecting the FMN of FdsB with the active-site molybdenum center of FdsA. According to the NADH-bound structure, the nicotinamide ring stacks onto the re-face of the FMN. However, NADH binding significantly reduced the electron density for the isoalloxazine ring of FMN and induced a conformational change in residues of the FMN-binding pocket that display peptide-bond flipping upon NAD+ binding in proper NADH dehydrogenases. Full Article
in Quantification of the affinities of CRISPR-Cas9 nucleases for cognate protospacer adȷacent motif (PAM) sequences [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency. Full Article
in A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning. Full Article
in Protecting the Environment in Areas Affected by Armed Conflict By feedproxy.google.com Published On :: Fri, 27 Sep 2019 13:10:01 +0000 Members Event 15 October 2019 - 6:00pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Dr Marja Lehto, Special Rapporteur, International Law Commission, UNDoug Weir, Research and Policy Director, The Conflict and Environment ObservatoryChair: Elizabeth Wilmshurst CMG, Distinguished Fellow, International Law Programme, Chatham House In 2011, the UN’s International Law Commission first included the ‘protection of the environment in relation to armed conflicts’ in its programme of work. Earlier this year, the Drafting Committee provisionally endorsed 28 legal principles intended to mitigate environmental degradation before, during and after conflicts. These addressed issues ranging from the pillage of natural resources to corporate environmental conduct and the environmental stress caused by population displacement. Special Rapporteur Dr Marja Lehto and a panel of experts will discuss some of the environmental issues arising from armed conflict and how these can be tackled. What are the International Law Commission’s recommendations and to what extent are stakeholders engaging with the work? In what sense are parties to the conflict, including governments, rebel groups and civil society, accountable for environmental devastation?And, looking beyond the environmental consequences of war, what is the role of climate change in driving insecurity and triggering conflict in the first place? Members Events Team Email Full Article
in Breaking the Habit: Why Major Oil Companies Are Not ‘Paris-Aligned’ By feedproxy.google.com Published On :: Mon, 07 Oct 2019 14:50:01 +0000 Invitation Only Research Event 23 October 2019 - 8:30am to 10:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Andrew Grant, Carbon Tracker InitiativeChair: Siân Bradley, Research Fellow, Energy, Environment and Resources, Chatham House The investment community is increasingly seeking to assess the alignment of their portfolios with the Paris Agreement. In a recent update to their Two Degrees of Separation report, Carbon Tracker assessed the capital expenditure of listed oil and gas producers against ‘well below’ 2C targets, and for the first time, against short-term actions at the project level.The speaker will present the key findings of the report and will argue that every oil major is betting heavily against a low-carbon world by investing in projects that are contrary to the Paris goals.This roundtable discussion will further explore the report findings and consider what investors, regulators and oil and gas companies can do to encourage alignment with the Paris Agreement ahead of 2020. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme Full Article
in The Indo-Pacific: Geostrategic Perspectives to 2024 - Workshop 3 By feedproxy.google.com Published On :: Mon, 14 Oct 2019 09:10:01 +0000 Invitation Only Research Event 17 October 2019 - 9:30am to 2:00pm Institut Francais des Relations Internationales, 27 rue de la Procession, 75740 Paris Cedex 15, France This closed-door roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024. Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence. The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga).Attendance at this event is by invitation only. Department/project Asia-Pacific Programme, Geopolitics and Governance, Sustainable and Inclusive Growth, Trade, Investment and Economics, Energy, Environment and Resources Programme, Geostrategic Outlook for the Indo-Pacific 2019-2024 Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article
in Iseoluwa Akintunde By feedproxy.google.com Published On :: Fri, 18 Oct 2019 11:46:40 +0000 Mo Ibrahim Foundation Academy Fellow, Energy, Environment and Resources Programme Biography Iseoluwa is Mo Ibrahim Fellow in the Energy, Environment and Resources programme where his research examines the international and national institutions responsible for the effectiveness of climate finance in developing countries, and how these frameworks interact with those of development assistance.He is qualified to practice law in Nigeria and has worked with a leading Nigerian law firm where he provided legal, policy and institutional advisories on environmental, natural resources, energy and climate change, and anti-corruption issues.He was an Erin JC Arsenault Fellow in Space Governance and holds a Master of Laws degree in Air and Space Law from the McGill Institute of Air and Space Law.Iseoluwa was previously a visiting researcher at the International Centre for Climate Change and Development, Bangladesh and the Department of Climate Change of the Federal Ministry of Environment in Nigeria where he researched on the governance of climate finance in developing countries.His broader research interests include the governance framework for the exploitation of the mineral resources in outer space. Areas of expertise Climate finance and development assistanceThe legal regime for the exploitation of the mineral resources in outer space, the Moon and celestial bodiesInternational air and space lawInternational law, international environmental law and governance Past experience 2019Researcher, Centre for International Governance Innovation, Waterloo Canada2018Visiting researcher, Department of Climate Change, Federal Ministry of Environment, Abuja Nigeria2018Visiting researcher, International Centre for Climate Change and Development, Dhaka Bangladesh 2013 - presentAssociate, Wole Olanipekun & Co., Lagos Nigeria Email @Ise0luwa LinkedIn Full Article
in Tackling Toxic Air Pollution in Cities By feedproxy.google.com Published On :: Mon, 28 Oct 2019 16:15:01 +0000 Members Event 27 November 2019 - 6:00pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Camilla Hodgson, Environment Reporter, Financial TimesDr Benjamin Barratt, Senior Lecturer in Chinese Environment, KCLDr Susannah Stanway MBChB MSc FRCP MD, Consultant in Medical Oncology Royal Marsden NHS Foundation TrustElliot Treharne, Head of Air Quality, Greater London AuthorityChair: Rob Yates, Head, Centre on Global Health Security, Chatham House Air pollution has been classified as a cancer-causing agent with evidence showing an increased risk of lung cancer associated with increasing levels of exposure to outdoor air pollution and particulate matter.Air pollution is also known to increase risks for other diseases, especially respiratory and heart diseases, and studies show that levels of exposure to air pollution have increased significantly in some parts of the world - mostly in rapidly industrializing countries with large populations.In coordination with London Global Cancer Week partner organizations, this event outlines the evidence linking air pollution and cancer rates in London and other major cities.Panellists provide a 360° picture of the impact of the rising incidence of cancer across the world, the challenges the cancer pandemic poses to the implementation of universal health coverage and the existing UK contribution to strengthening capacity in cancer management and research in developing countries. Department/project Global Health Programme Members Events Team Email Full Article
in Negative Emissions and Managing Climate Risks Scenarios By feedproxy.google.com Published On :: Thu, 31 Oct 2019 18:15:01 +0000 Research Event 4 July 2019 - 1:30pm to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE This half-day strategic workshop, organized by Chatham House and E3G, brought together key climate experts, policymakers and influential actors, especially in Europe, for a focused and facilitated discussion on the roles, risks and potentials of negative emissions technologies (NETs). An interactive scenario exercise will be conducted, drawing on a climate simulation tool developed by Climate Interactive, to consider the potential roles and risks of different NETs deployments to meet the Paris Agreement targets and to consider the international co-operation required to manage the pathway to net-zero emissions. Participants will explore the political opportunities, discuss different scenarios and risks and identify areas of interventions and collective action.The meeting is part of a series of events being held at Chatham House as part of London Climate Action Week (LCAW). Department/project Energy, Environment and Resources Programme, Bioenergy, Carbon Capture and Storage (BECCS) Full Article
in China's ivory bans: enhancing soft power through wildlife conservation By feedproxy.google.com Published On :: Wed, 06 Nov 2019 09:20:21 +0000 6 November 2019 , Volume 95, Number 6 Jonas Gamso Read online China has been a major market for elephant ivory for centuries. However, the Chinese government recently enacted bans on imports and exports of ivory (2015) and on the domestic ivory trade (2017). These bans appear to have come in response to intensive influence campaigns and public shaming from domestic and foreign activists, who cited declining elephant populations and highlighted China's role. However, this shaming-narrative is at odds with conventional wisdom regarding Chinese policy-making: China typically resists international pressures and its authoritarian government is thought to be largely insulated from domestic efforts by civil society groups. This article reconciles Beijing's ivory policy with these conventional beliefs about policy-making in China. I argue that the Chinese government saw unique benefits to banning the ivory trade, under growing international scrutiny, as doing so enhanced Chinese soft power while having very little impact on its sovereignty or development. Non-government organizations (NGOs) operating both inside and outside of China played a role as well: NGOs in China helped to shift Chinese public opinion towards favouring the bans, while those operating abroad led public relations efforts to publicize Chinese demand for ivory to foreign audiences. Efforts by the latter group of NGOs intensified pressure on the Chinese government to rein in the ivory market, while increasing the soft power benefits that banning ivory would bring to Beijing. Full Article
in A Transformative Agenda for Greater Sustainability in Trade By feedproxy.google.com Published On :: Fri, 15 Nov 2019 10:25:01 +0000 Corporate Members Event Nominees Breakfast Briefing Partners and Major Corporates 3 December 2019 - 8:00am to 9:15am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Christophe Bellmann, Associate Fellow, Hoffmann Centre for Sustainable Resource Economy, Chatham HouseCarolyn Deere Birkbeck, Associate Fellow, Global Economy and Finance Department and Hoffmann Centre for Sustainable Resource Economy, Chatham House International trade rules and policies are deeply relevant to environmental performance. On the one hand, trade flows, rules and policies can exacerbate environmental challenges as consumers regularly purchase goods produced or disposed of in unsustainable ways in other countries therefore 'exporting' environmental costs. On the other hand, trade rules and flows can be harnessed to support environmental agendas and impact commercial and trade prospects positively.The speakers will discuss the urgent need for greater political leadership and inclusive policy dialogue on environment and trade to address its development and competitiveness. Which priorities should form the heart of a forward-looking environment and trade 2.0 agenda in the context of the UN’s SDGs? What role can international trade play in helping deliver sustainable food and land use systems? And how can stakeholders promote the scaling-up of the many initiatives underway and serve as a vehicle for transformative change toward a more sustainable economy at the national and international level?This event is only open to Major Corporate Member and Partner organizations of Chatham House. If you'd like to attend, please RSVP to Linda Bedford.To enable as open a debate as possible, this event will be held under the Chatham House Rule. Members Events Team Email Full Article
in Exploring the Looming Water Crisis By feedproxy.google.com Published On :: Tue, 26 Nov 2019 16:12:28 +0000 28 November 2019 Gitika Bhardwaj Editor, Communications & Publishing, Chatham House @GitikaBhardwaj LinkedIn Loïc Fauchon President, World Water Council Loïc Fauchon, president of the World Water Council, speaks to Gitika Bhardwaj about the causes of water scarcity around the world and how best to implement sustainable solutions. GettyImages-686773184.jpg Dry sand and a narrow body of water near the Theewaterskloof Dam in South Africa which has had less than 20 per cent of its normal water capacity during recent water shortages. This dam, about 108km from Cape Town, is the main water source for residents of the city. Photo: Getty Images. One-quarter of humanity faces a looming water crisis, including the prospect of running out of water, which may seem inconceivable when 70 per cent of the Earth’s surface is water. Nevertheless up to 80 per cent of available surface and groundwater is being used every year and water demand globally is projected to increase by 55 per cent by 2050. Why is the world facing a crisis of water scarcity and what is driving the increasing demand for water? The first reason that is causing water stress around the world is the growing human population at the same time as the water supply has remained the same. Given that there are almost one billion more inhabitants on Earth every 15-20 years, this has led to a progressive deficit in the global water supply. The second reason is due to the uneven concentration of the global population. There is not a clear link between the presence of the population in some regions and the presence of water, in other words, water is not where we want it to be every time.For example, there is, what we call, a ‘triangle of thirst’ from southern Spain, to Pakistan, to the Horn of Africa and back again. In this triangle, you have around two billion people in a very water-scarce region.Comparatively, if you go to Russia or Canada, they have more water than they need in terms of the size of their population. So this is another crucial reason we are facing a crisis of water scarcity in some regions of the world – but not everywhere. Climate [change] will be the fruit on the cake. Currently we have global population growth and then later we will have climate change affecting water availability. But at this very moment, however, the problem for water suppliers and for political leaders is the demographic crisis we are facing – not the climate.Water use has grown at more than twice the rate of the human population over the last century in part due to industries, such as agriculture, which account for 70 per cent of global freshwater use. Given that food production will need to grow by up to 70 per cent by 2035 to feed the growing human population, how do we balance the use of water with the need to provide food? There are some solutions. The first is that we need to improve water efficiency in the agricultural sector. We need to have all around the world, but mostly in developing countries, a better capacity to increase the water efficiency of agriculture without increasing the use of industrial chemical products and to move, step-by-step, to an economical system of organic farming. It will take time – it will not be done in one or even five years but more likely over a generation – but it is the best way. Secondly, which could be a faster solution, is that we have to reduce all kind of food waste which represents around 30-40 per cent of all agricultural production. Agriculture is a large sector involving the growing of crops but also livestock. There’s not only waste in terms of consumption but also during the production line, for example, during the transportation of food products. So there is this, sort of, waste cycle which is very important to consider. If you are able to reduce the water waste during the production line by 30-40 per cent, then you use less water, obviously.The third solution is to be able to, step-by-step, change our consumption patterns. Use less meat, all kinds of agricultural products which need a lot of water etc. I think we will be obliged to do this over the next couple of decades, and we will probably have low animal protein diets in the future, which will mean we have to think of different ways to be able to provide food to the increasing global population.There are other industries that are water-intensive that also need to be looked at in terms of their water waste such as the clothing and automobile industries. One piece of paper, for example, takes about 100 litres of water to produce while one litre of milk takes about 1,000 litres of water. Another example is that one cup of coffee takes 150 litres of water – just one cup of coffee – that’s because there is not only the water you are drinking but the water needed to prepare the coffee beans and the water used in the materials that make the coffee cup and so on.So everything consumes water and that’s why humans will be obliged to consume less water over the coming years. More than one in three people globally do not have access to safe drinking water and more than 4 billion people lack adequate sanitation. How can waste water be more efficiently used and do you think global goals to provide everyone with safe and clean drinking water are still realistic? In French, we use a phrase, parent pauvre, which means poor relative. Most of the decisions concerning access to water are not acceptable in the long term. That’s why we at the World Water Council are pushing for the financing of water and sanitation goals [concurrently].For example, if you have a programme for a city to increase access to water for its citizens, they also need a sanitation programme. If we don’t do that, the mismatch that currently exists between water and sanitation will remain. There’s also another important solution which political leaders will be obliged to invest more in which is having more water coming from water reuse. If you produce water from water reuse processes then it means that it will likely have undergone sanitation treatment already which is a win-win solution [for providing safe and clean drinking water].It’s all moving slowly but I’m optimistic concerning the increasing consciousness of people regarding water pollution – for example the pollution of our rivers, seas and oceans – and I think we will move faster in the sanitation area than in the water access area over the next decade.Personally, I do not think that global goals to provide everyone with safe and clean drinking water [are the best solution]. I am more in favour of national and local commitments rather than global commitments. National and local efforts are stronger then [the rhetoric] around global goals where there is no authority to oversee the progress they are making. Only the population of a country or of a city can see if their leaders have done their job regarding providing access to safe and clean water. People queue up to collect water from taps fed by a spring in Newlands in 15 May 2017 in Cape Town, South Africa. South Africa's Western Cape region declared a drought disaster on 22 May 2017 as the province battled its worst water shortages for more than 112 years. Photo: Getty Images. With the depletion of global water supplies, how can governments avoid the politicization of water, as seen in cases such as the Nile River Basin and across the Middle East, to avoid conflicts over water? This is a complicated issue because politicians will always do politics so it will always be difficult to avoid attempts to politicize situations. But the key is dialogue, dialogue and dialogue. That is the only way to solve water conflicts as well as better management of water because, in some regions, some of these conflicts are arising from the mismanagement of water supplies – not because of water scarcity. If you look at Egypt and the US, people are consuming around 800 litres [of water] per day whereas in Europe people are consuming around 200 litres per day. But why is [water consumption] in Egypt, rather than Europe, the same as in the US? Because they have considerable water losses in industries such as agriculture.In addition, in the main cities like Cairo, there is not an adequate range of water networks, so, if in the future those living in Cairo are able to consume less water, they will need less water coming from the Nile River which will make politicization of water by politicians less likely. In the future, social unrest from water shortages is likely, however, I do not think it will ever lead to wars. Countries across the Middle East have invested in modern techniques, such as desalination plants, as an answer to water scarcity, but this can have a negative impact, notably on marine life. In contrast, some of the more ancient techniques, like rainwater harvesting, are being repurposed in cities around the world today. What is your view on these practices and what other solutions are available? There are a lot of solutions and desalination is among them. Currently probably 100 countries in the world are using, or preparing to use, desalination as a solution so it surely is an important solution. But at the same time, reused water is developing fast and is a much cheaper option than desalination. Nevertheless, the price of desalination has been decreasing over the past 20 years and is now less than $1 a cubic metre, whereas 15 years ago, it was $10 a cubic metre.Some of the negative impacts of desalination exist when you are separating the water from the salt, which can lead to disasters, for example, what has happened in the Persian Gulf. When Kuwait, Saudi Arabia, Bahrain and Qatar first used desalination treatments, the temperature of the sea was around 30°C, whereas today, it can be up to 40°C. This increasing sea temperature as a result of the desalination plants has contributed to changes in biodiversity. For example, we are seeing fish disappearing and even the growing population of giant jellyfish – which some desalination plants in Saudi Arabia are dealing with by using shredders which is another type of disaster.Furthermore, in some regions, we need to keep in mind that desalination is not only along the coast but it’s also in the middle of the land too. For example, in the Sahara region, like in Algeria or Morocco, the water coming from the ground is salted so you need to have desalination plants inland and not on the coast. But where they keep the salt inland, that salt mixes with the rain and enters the ground, thereby destroying some of the biodiversity there too. So it must be used prudently. Rainwater harvesting is a technique from centuries ago and I am a great supporter of it as a solution to water scarcity in India, particularly in Rajasthan, and I think it could also be part of the solutions in some places across Africa.That’s why I believe there needs to be an exchange of solutions because something which is successful here could be successful somewhere else. In this way, we need to be able to show a Senegalese farmer a solution which has been implemented elsewhere, such as in India, and show him this can work for you too – it’s sort of like when the Japanese built the Toyota by looking at the British Land Rover.With billions of people threatened by the global water crisis, increased water stress could lead to more ‘Day Zeroes’, a term used in 2018 as Cape Town in South Africa came dangerously close to running out of water. In your view, what will happen if the world doesn’t adequately address the global crisis of water scarcity?The increasing absence of water would mean not only the migration of humans to more water-abundant regions but also the absence of socioeconomic growth of any kind in some places because water scarcity will pose a risk to businesses who will be forced to move to new areas – from small businesses like a hairdresser to factories that are unable to produce any goods or provide any services. So not tackling the water crisis means not being able to tackle our own capacity to prosper by not protecting the environment we depend on.In Cape Town, there was a lack of rain in the city which contributed to the water crisis there but there was also a lack of water management. They knew they could have a lack of rain, and when you have a lack of rain, you have the obligation to prepare a reservoir of water for the year to the next year and so on but that did not happen.There is a French poem from Jean de La Fontaine about a grasshopper and an ant. The grasshopper just spends his time in the summer enjoying life but the ant keeps working hard throughout the summer to save all of his supplies for the winter. In this way, we need to be like the ant, preparing water supplies for today and for tomorrow.In the case of Cape Town, there was also another element, which was that the water supplies were being used by the central government as a tool to isolate the regional governor there who was part of the opposition. So the lack of water management was almost used as a political tool as we discussed earlier.Some say that the water scarcity we are seeing is because of climate change. Yes it is but there is also a lack of water management by humans. If you look at the people living throughout the centuries all the way to antiquity, you see that people around the world prepared reservoirs of water to keep water from the winter to the summer, from the one year to the next, whereas today, we are seeing bad water management. So, in this way, I believe climate change should not be the scapegoat of human error. Full Article
in Making the Business Case for Nutrition Workshop By feedproxy.google.com Published On :: Thu, 05 Dec 2019 12:15:01 +0000 Invitation Only Research Event 28 January 2020 - 9:30am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE A ground-breaking research project from Chatham House, supported by The Power of Nutrition, is exploring the business case for tackling undernutrition, micronutrient deficiencies and overnutrition. Companies across all sectors hold huge, transformative power to save countless lives and transform their own financial prospects. To act, they need more compelling evidence of the potential for targeted investments and strategies to promote better nutrition and create healthier, more productive workforces and consumers.At this workshop, Chatham House will engage business decision-makers in a scenario exercise that explores different nutrition futures and their commercial prospects in each before examining what different strategies business can pursue to maximize future profitability through investments in nutrition.Attendance at this event is by invitation only. Department/project Energy, Environment and Resources Programme Full Article
in Climate Change, Energy Transition, and the Extractive Industries Transparency Initiative (EITI) By feedproxy.google.com Published On :: Thu, 05 Dec 2019 15:45:01 +0000 Invitation Only Research Event 17 January 2020 - 9:30am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Climate change and energy transition are re-shaping the extractive sectors, and the opportunities and risks they present for governments, companies and civil society. As the central governance standard in the extractives sector, the EITI has a critical role in supporting transparency in producer countries.This workshop will bring together experts from the energy and extractives sectors, governance and transparency, and climate risk and financial disclosure initiatives to discuss the role of governance and transparency through the transition. It will consider the appropriate role for the EITI and potential entry points for policy and practice, and the potential for coordination with related transparency and disclosure initiatives. Please note attendance is by invitation only. Department/project Energy, Environment and Resources Programme Full Article
in COP26 Diplomatic Briefing Series: Outcomes of COP25 and What It Means for 2020 By feedproxy.google.com Published On :: Thu, 05 Dec 2019 16:15:01 +0000 Invitation Only Research Event 22 January 2020 - 4:30pm to 6:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Meeting summary pdf | 98.03 KB Event participants HE Raffaele Trombetta, Italian Ambassador to the UK, Co-Host, COP 26Archie Young, UK Lead Climate Negotiator, Cabinet Office Peter Betts, Associate Fellow, Energy, Environment and Resources Department, Chatham HouseChair: Professor Tim Benton, Research Director, Energy, Environment and Resources, Chatham House The UK will host the 26th Conference of the Parties (COP26) in November 2020 in Glasgow. In the run up, Chatham House is organizing a monthly briefing series targeted to:The diplomatic service based in London, in particular, staff of the London embassies who are reporting on climate change issues.Senior UK government civil servants, officials and politicians engaged in climate change.Academics, experts, business representatives and NGOs.The first briefing in the series focuses on the results from COP25 held in Madrid in December 2019 and what this means for 2020.This briefings series offer an opportunity to discuss, in an informal setting, the most pressing and complex climate issues of the day with UK and international government officials and experts. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme, COP26 Diplomatic Briefing Series Johanna Tilkanen Project Manager, Energy, Environment and Resources Department Email Full Article
in Just Circular Economy Transitions in Latin America By feedproxy.google.com Published On :: Tue, 10 Dec 2019 14:40:01 +0000 Invitation Only Research Event 11 December 2019 - 9:00am to 12 December 2019 - 5:00pm Montevideo, Uruguay To identify and promote collaborative opportunities for an inclusive and sustainable circular economy transition at the international level, a clearer understanding and discussions of the potential winners and losers of such a transition is needed. In short, a ‘win-win-win’ vision for the environment, people and the economy, needs to be built and credible pathways to achieving this vision.This research workshop, organized by Chatham House and UNIDO, will build on previous and ongoing research by Chatham House, and others, to drive forward an inclusive circular economy agenda and promote a just transition from linear to circular economic models. Chatham House, in collaboration with partners, aims to provide a strong evidence base of the opportunities and trade-offs in this transition from linear to circular models by robustly analysing the political economies in key regions in the developing world and engaging with leading stakeholders from governments, international organizations, civil society and the business community.Latin America is an important geographical region for the circular economy especially in view of the circular bioeconomy and the agenda around inclusiveness. Several countries are beginning to embrace the circular economy concept and related policies. This workshop will bring together circular economy leaders from policy, business and civil society across Latin American countries to identify and discuss challenges, large-scale positive sum opportunities, investment needs, existing alliances and the potential to scale up circular economy practices. The second day of the workshop includes site visits to various circular economy projects in Uruguay.Attendance at this event is by invitation only. Department/project Energy, Environment and Resources Programme, Building Transformative Alliances for an Inclusive Global Circular Economy Melissa MacEwen Project Manager, Energy, Environment and Resources Programme Email Full Article
in Subsidies and Sustainable Agriculture: Mapping the Policy Landscape By feedproxy.google.com Published On :: Tue, 10 Dec 2019 18:36:21 +0000 11 December 2019 Agricultural subsidies shape production and consumption patterns, with potentially significant effects on poverty, nutrition and other sustainability concerns. This paper maps the different types of support provided by governments to the agricultural sector, and highlights some of the complex political economy dynamics that underpin the relevant policies. Download PDF Christophe Bellmann Associate Fellow, Hoffmann Centre for Sustainable Resource Economy, Chatham House 2019-12-06-Wheat-Field-China.jpg Aerial view of a wheat field on 24 May 2019 in Linyi, Shandong Province of China. Photo: Getty Images. SummaryAgricultural subsidies, a mainstay of government policy, have a large part in shaping production and consumption patterns, with potentially significant effects as regards poverty, food security, nutrition, and other sustainability concerns such as climate change, land use practices and biodiversity.There are multiple types of direct and indirect support provided by governments to various actors in the agricultural sector; and in terms of political economy, there are complex dynamics underpinning the policies that sustain these subsidies.Overall, subsidies targeting producers have the most significant effect on production, and the greater trade-distorting effect. These subsidies promote domestic production and discourage imports, leading to overproduction that is largely disposed of on the international market, with the help of export subsidies. This can tend to intensify negative environmental agricultural practices, such as cultivating marginal land, unsustainable types of intensification, or incentivizing excessive pesticide and fertilizer use.On the other hand, producer subsidies that are not tied to output of a specific commodity (i.e. delinked) have far fewer distorting impacts and could help to deliver sustainable outcomes. For example, this type of subsidies can require crop diversification or be linked to conservation of permanent grassland.Subsidies that enable transfers to consumers, for example through food stamp programmes, also serve to delink production from consumption, can foster healthier diets, can play an important role in delivering food accessibility and security among low-income groups, and can represent one of the less trade-distorting subsidies.If subsidies are to be reformed to help promote healthier diets and encourage more sustainable production, it is essential to understand not only the type and amount of support that key countries provide, but also the domestic dynamics that can shape such policies.While price support, input subsidies or investment aids remain the central pillars of programmes in large developing countries such as Brazil, China or India, other economies – notably including the EU and Japan – focus on direct payments, support for general services and set-aside schemes, as well as significant border protection. The US, for its part, has tended to focus on subsidized insurance schemes and food programmes for poorer consumers.If subsidies are to deliver policy objectives, their design and implementation should delink production from consumption. For example, consumer subsidies designed to deliver nutrition and food security, or payments for environmental services to enable more environmentally friendly production systems, could prove to be the most effective, least trade-distorting means of achieving more sustainable and equitable agricultural production.The political economy of food means that the removal of subsidies is often highly sensitive, and tends to be met with significant resistance. However, reform that delinks support from production through a gradual transition process could ultimately prove successful in delivering effective subsidy schemes.Effective subsidy schemes must by design be truly result- and performance-based, supported by robust and objective indicators. At the same time, engaging multiple actors along key commodity value chains – including leading importing and exporting countries, traders and transporters – could lead to the development of international, commodity-specific arrangements that are able to deliver effective nutrition and sustainability goals. Full Article
in Circular Economy Finance Roundtable By feedproxy.google.com Published On :: Thu, 19 Dec 2019 11:00:01 +0000 Invitation Only Research Event 4 March 2020 - 1:00pm to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Agendapdf | 124.9 KB The circular economy minimises waste and keeps materials and products in circulation for as long as possible. It is increasingly regarded as a promising model for achieving the Sustainable Development Goals (SDGs) and the global climate goals of the Paris Agreement, as well as driving sustainable and resilient economic growth in both developed and emerging economies.The financial industry has a key role to play in scaling up circular practices and ensure the transition from a linear to a circular model. Interest and action from policymakers, the financial industry, and other stakeholders towards financing the circular economy is already emerging in the form of thematic circular economy funds and innovative financial vehicles, as well as new investment criteria, guidance and standards.However, as more activities around circular economy financing are emerging, questions that arise concern issues of common definitions and standards, consistency with green climate finance and development finance as well as distributive justice and good governance.Specific questions to be discussed during this event include:What is the current circular economy finance landscape in terms of initiatives, definitions, criteria and guidance?What are the roles of public and private funding and blended finance in financing the circular economy?What lessons can be learned from green climate finance initiatives and ESG related factors and risks? What types of financial products for small and medium sized enterprises (SMEs) in developing countries are required?How can the finance industry support inclusive and just transitions to the circular economy?This roundtable will bring together experts representing public and private finance and investment to discuss these questions and share best practise to forge pathways for joined up approach on circular economy finance.The roundtable will build on previous and ongoing research by Chatham House and others, to drive forward a global and inclusive circular economy agenda. Attendance at this event is by invitation only. Department/project Energy, Environment and Resources Programme, Building Transformative Alliances for an Inclusive Global Circular Economy Johanna Tilkanen Project Manager, Energy, Environment and Resources Department Email Full Article
in Seventh Meeting of the New Petroleum Producers Discussion Group By feedproxy.google.com Published On :: Mon, 06 Jan 2020 13:50:01 +0000 Research Event 11 November 2019 - 9:00am to 15 November 2019 - 6:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE The seventh annual meeting of the New Petroleum Producers Discussion Group brings together people from the group's member countries. The meeting includes an international discussion, a national seminar and a range of policy-relevant courses which have been specially tailored to the priorities of the group. This year’s international discussion focused on ‘Building Capacity and Institutions’.The New Petroleum Producers Discussion Group was first established in 2012 and provides a unique forum which brings together governments from over 30 new and prospective oil and gas producers to share their ideas and experiences. The group is jointly coordinated by Chatham House, the Commonwealth Secretariat, and the Natural Resource Governance Institute (NRGI).This event was hosted by the Ministry of Energy of Uganda. Department/project Energy, Environment and Resources Programme, New Petroleum Producers Discussion Group Full Article
in Review essay: Where is the Anthropocene? IR in a new geological epoch By feedproxy.google.com Published On :: Wed, 08 Jan 2020 13:46:10 +0000 8 January 2020 , Volume 96, Number 1 Read online Dahlia Simangan Several disciplines outside the natural sciences, including International Relations (IR), have engaged with the Anthropocene discourse in order to theorize their relevance and translate their practical value in this new phase of the Earth's history. Some IR scholars have called for a post-humanist IR, planet politics, a cosmopolitan view, and ecological security, among other approaches, to recalibrate the theoretical foundations of the discipline, making it more attuned to the realities of the Anthropocene. Existing discussions, however, tend to universalize human experience and gravitate towards western ontologies and epistemologies of living in the Anthropocene. Within this burgeoning scholarship, how is the IR discipline engaging with the Anthropocene discourse? Although the Anthropocene has become a new theoretical landscape for the conceptual broadening of conventional IR subjects, this review reveals the need for sustained discussion that highlights the differentiated human experiences in the Anthropocene. The existing IR publications on the Anthropocene locates the non-spatial narratives of vulnerability and historical injustice, the non-modernist understanding of nature, the agency of the vulnerable, and the amplification of security issues in the Anthropocene. It is in amplifying these narratives that the IR discipline can broaden and diversify the discourse on the Anthropocene and, therefore, affirm its relevance in this new geological age. Full Article
in The Indo-Pacific: Geostrategic Outlook to 2024 - Workshop 4 By feedproxy.google.com Published On :: Thu, 09 Jan 2020 11:15:01 +0000 Invitation Only Research Event 26 November 2019 - 9:30am to 12:00pm Gateway House, Stevens Street, Colaba This closed-door roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024.Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence.The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga). Department/project Asia-Pacific Programme, Geopolitics and Governance, Sustainable and Inclusive Growth, Trade, Investment and Economics, Energy, Environment and Resources Programme Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article
in Climate Action in 2020: Time to Focus on Forests By feedproxy.google.com Published On :: Tue, 14 Jan 2020 09:26:46 +0000 14 January 2020 Alison Hoare Senior Research Fellow, Energy, Environment and Resources Programme LinkedIn More ambitious policies to reduce deforestation are key to effective climate policy, but to succeed, they require three big changes in approach. 2020-01-14-ReforestBrazil.jpg Mahogany tree seedlings being taken to be planted out in the Amazon. Photo: Getty Images. December’s UN climate talks held in Madrid were aptly titled ‘Time for Action’. While little progress was made at the conference in establishing an international framework that would help to instigate this, there is still much scope for action in 2020. The need for this has become all too apparent as the impacts of climate change are increasingly seen around the world.One of the key areas where progress can be made in 2020 is in increasing the ambition of nationally determined contributions (NDCs), these being governments’ plans to take action in response to climate change. To date, 184 countries have submitted NDCs, yet the commitments that have been made fall far short of what is needed to avert catastrophic climate change.In 2020, however, many countries will be revising their NDCs, presenting an important opportunity to shift momentum; to date 79 countries have announced that they will be enhancing the ambition of their NDCs.The forest sector is one area where more ambitious targets are likely to be set, and indeed, at the Climate Action Summit in September 2019, more than 20 countries made new commitments for the conservation, reforestation and restoration of their forests.This will be essential. As is well documented, reducing deforestation is critical to reducing carbon emissions, while healthy and diverse forests are vital for adapting and increasing resilience to climate change.However, while it is important that ambitious targets are set, this is relatively easy; the bigger challenge lies in ensuring that these are achievable.This is all too apparent from experience thus far. In 2014, the New York Declaration on Forests set the goal to halve forest loss by 2020, and to end it by 2030. In addition, it included the goal to restore 150 million hectares of degraded landscapes and forestlands by 2020, and a further 200 million hectares by 2030.The declaration has been endorsed by over 50 countries, as well as business and civil society organizations, yet the 2020 goals are far from being reached – in the six years since the declaration was launched, it has been found that forest loss increased rather than declined, and only about 27 million hectares of land have been restored.What then is needed to ensure that the commitments being made by governments in their NDCs will actually be met? Three big changes are required.Firstly, a shift in perspective is needed in many countries to a more forest-sensitive approach to development, one that gives adequate recognition to the full range of values provided by forests, rather than primarily focusing on their role as a global carbon sink. These include their importance for local and national economies, for livelihoods and the well-being of forest-dependent peoples, and for biodiversity and the regulation of local climate and water systems.The focus on nature-based solutions at the international level offers potential to support this shift. However, it is critical that these are not seen as ‘niche’ approaches, and that countries identify what nature-based solutions mean for them, and how forests and tree-rich landscapes can best be integrated into their development strategies.Fundamental to achieving this will be further improvements in governance, and this is the second change that is required. Legal and institutional reforms are needed in many countries as well as significant investments in human and technical resources. This will enable processes to be strengthened, or put in place, so that equitable strategies can be developed and implemented – strategies that reflect a balance of the needs and priorities of the full range of stakeholders, including local and global, rural and urban, women and men, young and old.Financing will of course be critical for this, and the least developed countries in particular will be hindered in the actions they can take without additional finance. This is the third area of change that is needed, and it is to be hoped that the international community will make better progress on this in 2020. Forest and land-use options are often described as a cost-effective means of tackling climate change, as is noted in the Santiago Call for Action on Forests for example.This is not to say that these will be easy or cheap – as Chatham House has documented, experience of forest governance reform has shown that it takes significant funding and time to bring about deep-rooted change. However, the huge potential benefits that can result, for the citizens of forest-rich countries as well as for the planet, mean that forests and sustainable land-use are a good investment. Full Article
in Forecasting Forum 2020 By feedproxy.google.com Published On :: Wed, 15 Jan 2020 15:35:01 +0000 Invitation Only Research Event 17 February 2020 - 2:00pm to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Tim Benton, Research Director, Emerging Risks; Director, Energy, Environment and Resources Programme, Chatham HouseProfessor Paul Stevens, Distinguished Fellow, Energy, Environment and Resources Programme, Chatham HouseAntony Froggatt, Senior Research Fellow, Energy, Environment and Resources Programme, Chatham HouseChair: Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Programme The Forecasting Forum 2020 will present the latest thinking from the Chatham House Energy, Environment and Resources Department's senior research team on the dynamics that will affect fossil fuel and energy investments and markets in the year ahead.14:00 - 14:30 | Introduction and Climate Risks Outlook In the last decade, following the financial crisis, the literature on systemic risks has grown. Systemic risks occur when complex, non-linear, interconnected systems fail, often through relatively small perturbations, as their impacts cascade and amplify across the system. Within this context, climate change is a 'threat multiplier' with the risks increasing in scale, frequency and magnitude. Just as complex systems can pass thresholds and tip from a functional state to a non-functional state, so can societies and people’s attitudes. Together risk cascades or systemic risks and attitudinal tipping points have the potential to rapidly change the way the world works. Professor Tim Benton will open the Forecasting Forum 2020 with reflections on what this might mean for the pace and linearity of the fossil fuel transition.14:30 - 15:30 | Session 1: An Outlook on Oil Prices in 2020In this session, Professor Paul Stevens will argue that the recent events associated with the assassination of Iranian General Qasem Soleimani have exacerbated the sensitivity of oil markets to political events and brought 'geopolitics' back into global oil prices. Up to 2014, geopolitics played a key role in determining oil prices in the paper markets where perceptions and expectations ruled. By 2014, the world was so oversupplied with real oil barrels that the oil price collapsed and little attention was given to geopolitical events as geopolitics became marginalized in the determination of crude oil prices. However, recent events in the Middle East suggest that prices will become increasingly volatile but, at the same time, benefit from a rising geopolitical premium.15:45 - 16:45 | Session 2: An Outlook for Energy in 2020Recent years have brought significant disruption to the European power sector. Not only are many of Europe’s major utilities restructuring their businesses in light of decarbonization and technological developments but Brexit has distracted - and detracted from - efforts to create more systemic energy linkages between the UK and the rest of Europe. During his presentation, Antony Froggatt will draw on his ongoing research to outline what he believes are the prevailing challenges and opportunities for the European power sector over the coming year while highlighting some of the most significant global trends.Please note, attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme, Sustainable Transitions Series Chloé Prendleloup Email Full Article
in Will a Devastating Bushfire Season Change Australia’s Climate Stance? By feedproxy.google.com Published On :: Thu, 23 Jan 2020 09:20:27 +0000 23 January 2020 Madeleine Forster Richard and Susan Hayden Academy Fellow, International Law Programme @maddiefors LinkedIn Professor Tim Benton Research Director, Emerging Risks; Director, Energy, Environment and Resources Programme @timgbenton Google Scholar With Australians experiencing first-hand the risks of climate change, Madeleine Forster and Tim Benton examine the influencers, at home or abroad, that could push the government towards more action. 2020-01-23-FireNSW.jpg Residents look on as flames burn through bush on 4 January 2020 in Lake Tabourie, NSW. Photo: Getty Images. The 2019–20 fire season in Australia has been unprecedented. To date, an estimated 18 million hectares of fire has cut swathes through the bush – an area greater than that of the average European country and over five times the size of blazes in the Amazon.This reflects previous predictions of Australian science. Since 2008 and as recently as 2018, scientific bodies have warned that climate change will exacerbate existing conditions for fires and other climatic disasters in Australia. What used to be once-in-a-generation fires now re-appear within 10–15 years with increased ferocity, over longer seasons.In a country known for climate denial and division, debate has erupted around bushfire management and climate change. One of these is whether controlled burns are the answer to Australia’s climate-affected fire conditions.There is no single risk reduction strategy. Controlled burning remains key, if adapted to the environment and climate. But when three out of four seasons in a year can support destructive bushfires, there are clear limits to what controlled burning and other fire management techniques can achieve. Other ‘adaptation’ measures are also likely to provoke intense debate – including bush clearance. As one Australian expert offered to highlight where Australia has got to, families should probably not go on holiday to bush and beach during the height of summer when temperatures and fire risk peaks. So, unless Australia is prepared to debate radical changes to where people live and how land is used, the limits to adaptation imply the need for mitigation. This means supporting ambitious global greenhouse emissions reductions targets. As research from Victoria, one fire-prone state in Australia, highlights, ‘the emissions pathway we follow is the largest determinant of change to many variables [such as temperature] beyond the next few decades.’Can Australia become a more active global partner on emissions?Australia accounts for just over one per cent of global emissions, so reducing domestic emissions – even though on a per capita basis they are the highest in the world – will not reduce Australia’s climate risk. Showing international leadership and supporting a powerful coalition of the willing to tackle climate change is the only way ahead. By showing a willingness to adopt climate ambition, Australia can help more constructive worldwide action, and thereby reduce its own risk exposure. Leading by example is a politically difficult issue for Australia. Prime Minister Scott Morrison was re-elected in May 2019 on an economic stability platform, and a promise not to imperil employment growth through climate action. Australia has contested UN estimates that it will not meet its existing modest goals for domestic emissions, by seeking to rely on carryover credits from action under the Kyoto Protocol as proof of progress.It has also distanced itself from concerns over global supply and demand in fossil fuels. Australia remains a global supplier for fossil fuels, including coal – the nation’s coal exports accounted for $67 billion in revenues in 2019 in an expanding but changing Asian market, supplying ‘some of the cheapest electricity in the world’.Possible influencers of changeWith Australians experiencing first-hand the risks of climate change, there is already pressure to do more. Many are sceptical this will translate into domestic targets or export policies that give Australia the moral authority to ask for more action on the global stage.Here, diverse groups who share a common interest in seeing Australia recover from the bushfires and address future climate risks could be key.Importantly this includes rural and urban-fringe communities affected by the bushfires. They were part of Morrison’s traditional supporter-base but are angry at the government’s handling of the crisis and increasingly see how tiptoeing around emissions (including exports) has also ‘buried’ open discussion at home on climate-readiness.Australian states could also find themselves taking a lead role. Virtually all jurisdictions have now committed to their own goals, most based on zero-carbon goals by 2050 (as has New Zealand). These can support modelling for Australia’s energy transition from coal, through gas, to market competitive renewables, while also help to ensure this reflects community expectations on jobs, electricity prices and other costs. Other emerging voices include the insurance and banking sectors (the Reserve Bank of Australia warned of the long-term financial stability risks of climate change before the fires) and indigenous Australians (one group of Torres Strait Islanders have filed a complaint to the UN Human Rights Committee which, if heard, will place Australia’s emissions record under the spotlight again). Their challenge now is finding a common language on what a cohesive approach to addressing climate change risk looks like. The international picture is mixed. The United States’ poor federal climate policy is a buffer for Australia. French President Emmanuel Macron has tried to raise the cost of inaction for Australia in current EU–Australia trade negotiations, but many large emitters in the Indo-Pacific region remain key Australian trading partners, investors and buyers of Australian coal. In the meantime, the United Kingdom is preparing for the meeting of parties to the Paris Agreement in Glasgow in November. A key global event following Brexit, the UK will no doubt be hoping to encourage a leadership circle with national commitments that meet global need to make the Glasgow meeting a success.The UK public has expressed enormous sympathy for Australia in the bushfires and outrage over ‘climate denialism.’ Australia’s experience will be a cautionary tale of the effects of climate change at the meeting. Could the UK also support Australia to become a less reluctant partner in global climate action? Full Article
in Maintaining Connections: How Might the UK Remain Engaged in the EU's Climate and Energy Strategies? By feedproxy.google.com Published On :: Thu, 23 Jan 2020 10:35:01 +0000 Invitation Only Research Event 3 March 2020 - 10:30am to 12:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE As the UK leaves the EU and the formal negotiations on the future relationship begins, this workshop will discuss any immediate changes and review the short and medium term impacts of Brexit on the energy sector. The workshop will look to cover:The implications for UK business and system operations of the UK leaving the Internal Energy Market.Current and future investment trends in the UK energy system.The trade of electricity and gas over inter-connectors.The need for the development of a new EU-UK operational framework mechanism.The UK's EU withdrawal agreement and the operation of the Single Electricity Market (SEM) across Ireland. Options for the UK outside of the EU Emissions Trading System (ETS) and the impact on carbon prices.This workshop is part of a programme funded by the UK Energy Research Centre on Brexit and the UK’s Net Zero Energy Policy being run by the University of Warwick and Chatham House.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme Chloé Prendleloup Email Full Article
in Hiroki Sekine By feedproxy.google.com Published On :: Thu, 23 Jan 2020 13:30:55 +0000 Visiting Fellow, Asia-Pacific Programme Biography Hiroki Sekine is visiting fellow with the Asia-Pacific Programme at Chatham House.He was director of the policy and strategy office for financial operations at JBIC from July 2016 until June 2019 and, most recently, senior advisor to the corporate planning department at the Japan Bank for International Cooperation (JBIC).During this time, Hiroki led an internal taskforce to facilitate a trilateral partnership between the US, Australia and Japan, aiming to enhance infrastructure development under the Free and Open Indo-Pacific Strategy.He has led project finance deals for power and petrochemical projects in Asia, the Middle East and South America. In 2018, Hiroki was appointed as adjunct professor at Kyoto University.Hiroki Sekine is based at Chatham House until June 2021, hosted by the Asia-Pacific programme. During his fellowship, Hiroki is undertaking research on infrastructure development in the Asia-Pacific. Areas of expertise Infrastructure development policy in the Asia-Pacific regionFinance (incl. green finance, project finance, and sovereign finance)Public finance policy (incl. multilateral finance agencies, development finance agencies) Past experience 2019 - presentSenior advisor, Corporate Planning Department, Japan Bank for International Cooperation2016-19 Director, Policy and Strategy Office for Financial Operations, Japan Bank for International Cooperation2015-16 Advisor, Credit Analysis Department, Japan Bank for International Cooperation2013-15Director, Division 2, Corporate Finance Department2011-13Director, Power and Water Finance Department, Japan Bank for International Cooperation2010-11Advisor, Asia and Oceania Finance Department, Japan Bank for International Cooperation2008-10Deputy Director, Division2, Asia and Oceania Finance Department, Japan Bank for International Cooperation2005MSc in Finance, London Business School, University of London1995B.A. in Economics, University of Tokyo +44 (0)20 7314 3626 Email Full Article
in China's 2020: Economic Transition, Sustainability and the Coronavirus By feedproxy.google.com Published On :: Tue, 04 Feb 2020 21:15:01 +0000 Corporate Members Event 10 March 2020 - 12:15pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Dr Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham HouseDavid Lubin, Associate Fellow, Global Economy and Finance Programme, Chatham House; Managing Director and Head of Emerging Markets Economics, CitiJinny Yan, Managing Director and Chief China Economist, ICBC StandardChair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House Read all our analysis on the Coronavirus ResponseThe coronavirus outbreak comes at a difficult time for China’s ruling party. A tumultuous 2019 saw the country fighting an economic slowdown coupled with an increasingly hostile international environment. As authorities take assertive steps to contain the virus, the emergency has - at least temporarily - disrupted global trade and supply chains, depressed asset prices and forced multinational businesses to make consequential decisions with limited information. Against this backdrop, panellists reflect on the country’s nascent economic transition from 2020 onward. What has been China’s progress towards a sustainable innovation-led economy so far? To what extent is the ruling party addressing growing concerns over job losses, wealth inequality and a lack of social mobility? And how are foreign investors responding to these developments in China? Members Events Team Email Full Article
in The prospects of carbon dioxide removal in climate policymaking within the United States By feedproxy.google.com Published On :: Fri, 14 Feb 2020 10:40:01 +0000 Research Event 19 November 2019 - 9:00am to 5:00pm School of Law, University of California, Davis Agendapdf | 158.8 KB Meeting Summarypdf | 207.92 KB This meeting formed part of a programme of work which investigates the role of negative emissions technologies (NETs) in achieving the Paris Agreement climate targets. Previous meetings held in London and Brussels have looked at integrating negative emissions into EU policy-making, the implications and degree to which NETs, and in particular bioenergy with carbon capture storage (BECCS), can be an effective climate mitigation tool. This meeting focused on the possible deployment pathways of NETs and alternatives to BECCS for the US in particular, in the context of geographical constraints and socioenvironmental implications, the role of the private sector, and appropriate governance and finance mechanisms. Department/project Energy, Environment and Resources Programme, Bioenergy, Carbon Capture and Storage (BECCS) Melissa MacEwen Project Manager, Energy, Environment and Resources Programme Email Full Article
in The Indo-Pacific: Geostrategic Outlook From Now to 2024 - Workshop 5 By feedproxy.google.com Published On :: Mon, 17 Feb 2020 14:25:01 +0000 Invitation Only Research Event 18 February 2020 - 12:00pm to 4:30pm Langafonua Centre This roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024. Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence. The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga). Department/project Asia-Pacific Programme, Sustainable and Inclusive Growth, Trade, Investment and Economics, Energy, Environment and Resources Programme Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Full Article