CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.

Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and airway hyperresponsiveness. We explored the hypothesis that nicotine increases NGF by reducing lung fibroblast (LF) microRNA-98 (miR-98) and PPARγ levels, thus promoting airway remodeling. Levels of NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred to as ET-1), and collagen (COL1A1 and COL3A1) were measured in human LFs isolated from smoking donors, in mouse primary LFs exposed to nicotine (50 μg/ml), and in whole lung homogenates from mice chronically exposed to nicotine (100 μg/ml) in the drinking water. In selected studies, these pathways were manipulated in LFs with miR-98 inhibitor (anti-miR-98), miR-98 overexpression (miR-98 mimic), or the PPARγ agonist rosiglitazone. Compared with unexposed controls, nicotine increased NGF, FN1, ET-1, COL1A1, and COL3A1 expression in human and mouse LFs and mouse lung homogenates. In contrast, nicotine reduced miR-98 levels in LFs in vitro and in lung homogenates in vivo. Treatment with anti-miR-98 alone was sufficient to recapitulate increases in NGF, FN1, and ET-1, whereas treatment with a miR-98 mimic significantly suppressed luciferase expression in cells transfected with a luciferase reporter linked to the putative seed sequence in the NGF 3'UTR and also abrogated nicotine-induced increases in NGF, FN1, and ET-1 in LFs. Similarly, rosiglitazone increased miR-98 and reversed nicotine-induced increases in NGF, FN1, and ET-1. Taken together, these findings demonstrate that nicotine-induced increases in NGF and other markers of airway remodeling are negatively regulated by miR-98.

The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN–GAA–Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by ∼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4–7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA.

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The functional mechanisms of multidomain proteins often exploit interdomain interactions, or “cross-talk.” An example is human Pin1, an essential mitotic regulator consisting of a Trp–Trp (WW) domain flexibly tethered to a peptidyl-prolyl isomerase (PPIase) domain, resulting in interdomain interactions important for Pin1 function. Substrate binding to the WW domain alters its transient contacts with the PPIase domain via means that are only partially understood. Accordingly, we have investigated Pin1 interdomain interactions using NMR paramagnetic relaxation enhancement (PRE) and molecular dynamics (MD) simulations. The PREs show that apo-Pin1 samples interdomain contacts beyond the range suggested by previous structural studies. They further show that substrate binding to the WW domain simultaneously alters interdomain separation and the internal conformation of the WW domain. A 4.5-μs all-atom MD simulation of apo-Pin1 suggests that the fluctuations of interdomain distances are correlated with fluctuations of WW domain interresidue contacts involved in substrate binding. Thus, the interdomain/WW domain conformations sampled by apo-Pin1 may already include a range of conformations appropriate for binding Pin1's numerous substrates. The proposed coupling between intra-/interdomain conformational fluctuations is a consequence of the dynamic modular architecture of Pin1. Such modular architecture is common among cell-cycle proteins; thus, the WW–PPIase domain cross-talk mechanisms of Pin1 may be relevant for their mechanisms as well.

Phospholipase Cε (PLCε) is activated downstream of G protein–coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core.

In animals, the response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of hypoxia-inducible transcription factor α (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the cellular slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-phase kinase-associated protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full-length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies, TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles.

DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme and transcriptional coactivator and is critical for tumor metabolism. In cancer cells, native tetrameric PKM2 is phosphorylated or acetylated, which initiates a switch to a dimeric/monomeric form that translocates into the nucleus, causing oncogene transcription. However, it is not known how these post-translational modifications (PTMs) disrupt the oligomeric state of PKM2. We explored this question via crystallographic and biophysical analyses of PKM2 mutants containing residues that mimic phosphorylation and acetylation. We find that the PTMs elicit major structural reorganization of the fructose 1,6-bisphosphate (FBP), an allosteric activator, binding site, impacting the interaction with FBP and causing a disruption in oligomerization. To gain insight into how these modifications might cause unique outcomes in cancer cells, we examined the impact of increasing the intracellular pH (pHi) from ∼7.1 (in normal cells) to ∼7.5 (in cancer cells). Biochemical studies of WT PKM2 (wtPKM2) and the two mimetic variants demonstrated that the activity decreases as the pH is increased from 7.0 to 8.0, and wtPKM2 is optimally active and amenable to FBP-mediated allosteric regulation at pHi 7.5. However, the PTM mimetics exist as a mixture of tetramer and dimer, indicating that physiologically dimeric fraction is important and might be necessary for the modified PKM2 to translocate into the nucleus. Thus, our findings provide insight into how PTMs and pH regulate PKM2 and offer a broader understanding of its intricate allosteric regulation mechanism by phosphorylation or acetylation.

Defining discontinuous antigenic epitopes remains a substantial challenge, as exemplified by the case of lipid transfer polyproteins, which are common pollen allergens. Hydrogen/deuterium exchange monitored by NMR can be used to map epitopes onto folded protein surfaces, but only if the complex rapidly dissociates. Modifying the standard NMR-exchange measurement to detect substoichiometric complexes overcomes this time scale limitation and provides new insights into recognition of lipid transfer polyprotein by antibodies. In the future, this new and exciting development should see broad application to a range of tight macromolecular interactions.

Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport.

Centrioles are key eukaryotic organelles that are responsible for the formation of cilia and flagella, and for organizing the microtubule network and the mitotic spindle in animals. Centriole assembly requires oligomerization of the essential protein spindle assembly abnormal 6 (SAS-6), which forms a structural scaffold templating the organization of further organelle components. A dimerization interaction between SAS-6 N-terminal “head” domains was previously shown to be essential for protein oligomerization in vitro and for function in centriole assembly. Here, we developed a pharmacophore model allowing us to assemble a library of low-molecular-weight ligands predicted to bind the SAS-6 head domain and inhibit protein oligomerization. We demonstrate using NMR spectroscopy that a ligand from this family binds at the head domain dimerization site of algae, nematode, and human SAS-6 variants, but also that another ligand specifically recognizes human SAS-6. Atomistic molecular dynamics simulations starting from SAS-6 head domain crystallographic structures, including that of the human head domain which we now resolve, suggest that ligand specificity derives from favorable Van der Waals interactions with a hydrophobic cavity at the dimerization site.

RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction.

Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex.

L. Oeding
Trans. Moscow Math. Soc. 83 (), 227-250.
Abstract, references and article information

A. Kh. Khachatryan, Kh. A. Khachatryan and A. Zh. Narimanyan
Trans. Moscow Math. Soc. 83 (), 183-200.
Abstract, references and article information

H. G. Kazaryan and V. N. Margaryan
Trans. Moscow Math. Soc. 83 (), 151-181.
Abstract, references and article information

A. V. Silantyev
Trans. Moscow Math. Soc. 83 (), 75-149.
Abstract, references and article information

A. G. Sergeev, A. Kh. Khachatryan and Kh. A. Khachatryan
Trans. Moscow Math. Soc. 83 (), 55-65.
Abstract, references and article information

M. A. Stepanova
Trans. Moscow Math. Soc. 83 (), 1-13.
Abstract, references and article information

Minerals and Metals for a Low-Carbon Future: Implications for Developing Countries 30 October 2017 — 5:00PM TO 8:00PM Anonymous (not verified) 13 October 2017 Chatham House, London

This roundtable will explore two sides of minerals and metals for a low-carbon future - the growing demand for metals required for low-carbon technology and the technological and policy innovations that will be required to manage the carbon footprint of the mining sector and its wider energy and industrial linkages. Based around a presentation and scenarios developed by the World Bank, this roundtable discussion will assess which strategic metals will likely rise in demand in order to deliver a low-carbon future, before exploring the possible implications for resource-rich developing countries. In particular, what does a growing demand of minerals for a clean energy future mean for governments and industry, and how might developing countries benefit from this trend? What impact might growth of the mining sector have on a sustainable and climate-smart development? Can renewable energy and other clean tech innovations in the mining industry help reduce the carbon footprint of the sector and related industries, and under what circumstances? And how fit-for-purpose are current donor approaches to the mining sector in an increasingly carbon-constrained world?

Attendance at this event is by invitation only.

Mining and the Circular Economy: Implications for the Minerals and Metals Industries 6 November 2017 — 4:00PM TO 5:30PM Anonymous (not verified) 31 October 2017 Chatham House, London

A New Era for China: Implications for the Global Mining and Metals Industries 18 June 2018 — 9:00AM TO 10:30AM Anonymous (not verified) 8 June 2018 Chatham House, London

Since the turn of the century, China’s demand for resources has dominated global headlines. It’s rapid demand growth through the early 2000s sparked the beginning of the commodities ‘super cycle’, and encouraged a growing Chinese presence in international mining, and in global metals and minerals markets. More recently, its transition toward the ‘new normal’ of slower but higher quality growth has underpinned the sudden slowdown in global commodities demand.

Drawing on China’s domestic ambitions, as set out in the 19th party congress, and on its wider strategic ambitions through the Belt and Road Initiative, the speaker will set out his thoughts on China’s next era of growth, and its likely implications for international mining investment and global metals and minerals markets.

Flexible Distribution Systems: New Services, Actors and Technologies 4 September 2018 — 9:00AM TO 10:30AM Anonymous (not verified) 31 July 2018 Chatham House, London

The pace of the energy transition is accelerating. Solar and wind are dramatically falling in cost and displacing fossil fuel generators. Simultaneously, the rapid uptake of electric vehicles and battery storage systems are beginning to send shock-waves through the electricity sector.

As the proportion of distributed energy resources (DERs) connected to the distribution network grows, a significant opportunity is beginning to present itself. What if the concerns of renewable integration and associated costs could be solved by the smart integration of these DERs?

By properly valuing the services DERs can provide, actively managing the distribution system and creating new market places, might a truly renewable electricity system capable of supporting the electrification of heat and transport be possible?

During this roundtable, Andrew Scobie, CEO of Faraday Grid, will provide an overview of the challenges and opportunities faced within the distribution network and explain why the current system is no longer fit for purpose.

This is the inaugural event in the Energy Transitions Roundtable (ETR) series.

Korea's New Energy Policy and Implications for LNG Imports 3 October 2018 — 9:00AM TO 10:30AM Anonymous (not verified) 17 September 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

The new energy policy of Moon Jae-In’s administration aims to swing radically from coal and nuclear towards renewables and LNG for power generation. During the last 12 months the priority given to the expansion of renewable energy has been overwhelming and the support for the expansion of gas not as strong as many observers had expected. The 13th gas supply and demand plan announced in Spring 2018 confirmed the trend. Based on this projection, Professor K. Paik will discuss how this new energy policy will affect Korea’s LNG imports strategy and what are the implications of Korea’s northern policy towards this LNG supply strategy and pipeline gas imports to the Korean Peninsula.

Attendance at this event is by invitation only.

Realizing the Potential of Extractives for Industrial and Economic Development 18 October 2018 — 5:30PM TO 7:00PM Anonymous (not verified) 3 October 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Over the past two decades, the extractives industries have risen in importance for many low- and middle- income countries their prospects for economic development and poverty reduction. During a period of rising commodities prices, the development of extractives became increasingly attractive to both governments and companies. There was - and remains - much discussion about their potential to support inclusive development.

However, there are also risks and uncertainties associated with the extractives industries and many things can, and do, go wrong. Fluctuations in commodity prices can be hard to manage and can lead to considerable fiscal pressures. In the longer-term, climate change and the various policy responses to this, will profoundly affect the extractives sector as renewables replace fossil fuels in the global energy mix.

Managing the extractives sectors will therefore remain highly challenging especially in low-income countries where institutions are often weak. This roundtable will bring together some of the foremost academics and practitioners working in the extractives industries and also in economic development to discuss a major new UNU-WIDER study Extractive Industries: The Management of Resources as a Driver of Sustainable Development.

Attendance at this event is by invitation only.

The Electric Vehicle Revolution: Impacts on Oil Economies and Industry 24 January 2019 — 8:15AM TO 9:45AM Anonymous (not verified) 3 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Electric vehicle (EV) deployment is gathering pace: the Norwegian government thinks that EV subsidies will be unnecessary by 2025 as they reach parity with diesel and petrol vehicles.

China has stipulated that EVs comprise 12 per cent of vehicle sales by 2020 while more governments are committing to banning diesel and petrol vehicles.

These developments are expected to be replicated as urban air pollution rises up the political agenda while technological developments and falling costs have given rise to ambitious forecasts on the increase in the deployment of EVs and the demise of the internal combustion engine.

Considering this, the presentations and initial discussion focus on:

• The influence of new technologies on the automotive landscape, including autonomous vehicles.
• How the automotive and oil companies are adjusting their business models to accommodate and encourage the rise in EVs.
• The risks and opportunities for the deployment of EVs for incumbents and new market actors.
• The role of government for example in public procurement and infrastructure development.
• The potential for modal shift and its impact on oil demand.

The discussion then seeks to explore the need for benchmarks of change including data and metrics to understand the changing risk landscape and the implications for different actors.

Finally, the discussion focuses on the speed of transformation and what this means for existing and new market actors.

Power Sector Transformation, New Market Dynamics and Geopolitical Implications 7 November 2018 — 8:00AM TO 9:30AM Anonymous (not verified) 6 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

The global electricity sector is experiencing profound change due to a confluence of technological innovation, environmental policies and regulatory reform. The effect is most obvious in the EU28, Australia and parts of North America.

However, this is just the beginning and the success of the next phase of electricity sector transformations hinges on enhancing system flexibility to facilitate unhindered low-cost deployment of renewables. It remains to be seen how utilities will seek to navigate this second phase of electricity transformations.

This session starts with a presentation and discussion that focuses on:

• Public and private sector risks of the transformation of the power sector, changes in generation mix and their implications for supply chain, employments and investment patterns.
• The role of government and the regulatory framework in light of changing market structure, new entrants and big data.
• Wider geopolitical issues including the implication for fossil fuel producers and the rise in demand for new materials and changes in land use.
• The possible implications on the power sector on the electrification of heat and transport.

The discussion then moves to the speed of transformation and what this means for existing and new market actors.

The Global Implications of China's Energy Revolution 4 March 2019 — 9:00AM TO 10:30AM Anonymous (not verified) 7 February 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Ten years ago, it would have been difficult to believe that China – the world’s largest greenhouse gas emitter – would be one of the global leaders in some elements of clean energy development and deployment. With increasing air pollution and predominantly coal-fired power generation fueled by a booming economy and population, China has had to rethink its approach to environmental protection and climate mitigation.

Strong government signalling and national policies have led to the construction of the world’s largest fleets, wind farms and solar photovoltaic arrays in an effort to reduce national GDP intensities of energy and CO2 emissions. How has the availability of large amounts of capital, and the number of state-owned companies with soft budgetary constraints, helped contribute to this?

Against this backdrop, this event will consider how China must re-evaluate its approach to energy security – coal made up the majority of the country’s energy in 2016, followed by oil, of which 65 per cent had to be imported – despite the country being one of the pioneers of renewable energy. This event will look at how, in delivering on its clean energy objectives, China could redefine the traditional energy security paradox and in fact become more resilient to previously overlooked vulnerabilities.

The EU’s Un-Common Agricultural Policy 21 October 2019 — 8:30AM TO 10:00AM Anonymous (not verified) 27 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Sino-Russian Gas Cooperation: Power of Siberia I and II and Implications for Global LNG Supplies 27 November 2019 — 8:30AM TO 9:30AM Anonymous (not verified) 19 November 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

In a new event in the Sustainable Transitions series, the speaker will present an update of Sino-Russian gas cooperation.

To give a comprehensive account of their impact on global liquefied natural gas (LNG) supplies, he will discuss the following points:

• Gas is scheduled to start flowing from the Power of Siberia I (POS) on 2 December 2019. But what is the background of development of POS 1 and what is its current status and prospects?
• What are the chances of exporting gas through the proposed Altai pipeline? Why is the Mongolia export route so significant? And how will it affect the Central Asian Republics and in particular Turkmenistan’s gas export to China?
• What are the implications of both POS I and Altai gas via Mongolia route in the context of global LNG supply?
• What are the prospects for multilateral pipeline gas cooperation in northeast Asia?
• What are the implications for other Arctic onshore LNG supply, in particular, for Novatek’s Yamal LNG and Arctic LNG 1 and 2 to China on top of POS 1 and Altai gas?

Attendance at this event is by invitation only.

Impact of the US Election on Global Climate Politics 25 November 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 16 November 2020 Online

Panellists discuss how Joe Biden’s victory will impact international efforts to tackle climate change. Will climate finally become a common area for global cooperation?

Joe Biden’s victory over Donald Trump is already having a positive impact on international efforts to tackle climate change. Leaders from across the world, including the UK, Canada, Australia and Fiji, have used their first messages to the President-elect to draw attention to the climate crisis.

Biden has promised to re-join the global community in its commitment to the Paris Agreement – but this could be the easy part. More difficult will be whether and how Biden is able to deliver his ambitious climate plan, and how effectively he is able to integrate climate change into foreign policy efforts and national security strategies.

Global climate action has also moved forward in the last four years. The European Union recently pledged to become climate neutral by 2050, and China, Japan and South Korea have committed to achieving carbon neutral economies.

How will the US re-enter this global landscape of distributed leadership and what difficulties does it face? Will the US be willing to work within a competitive partnership with the EU and China? How will Biden’s win change the dynamic of COP26 next year? 

Moving Food up the Political Agenda 14 December 2020 — 3:00PM TO 4:30PM Anonymous (not verified) 8 December 2020 Online

How can food system transformation be woven into high level biodiversity, nutrition and climate forums in 2021?

Adverse impacts on food security are expected to worsen as global temperatures continue to rise. As well as feeling the impacts of climate change, food systems drive it in a number of ways. Not only do food systems contribute more to greenhouse gas emissions than any other parts of our lives, they are also the leading driver of biodiversity loss, the largest cause of deforestation and occupy the most land globally.

On our current trajectory, 1.5°C of warming could become a reality in the next 5-10 years. Transforming food systems to meet climate, biodiversity and food security goals is crucial. If left to continue, food alone could take us over 1.5°C this century – even with maximum efforts in the energy sector.

Unprecedented levels of action to transform food systems is required over the next decade. The coming year is described as a ‘super year’ given the numerous high-level global events taking place that cover climate, biodiversity and food security. The year ahead has also been identified as the final opportunity to bring global commitments in line with the goals of the Paris Agreement.

What can be achieved in the super year? How can food system transformation be woven into high level biodiversity, nutrition and climate forums during the super year? How can momentum from the super year be built upon, to ensure meaningful action is taken over the next decade?

What's next for environmental peacebuilding? Lessons learned and opportunities from conflict-affected states 17 February 2021 — 3:00PM TO 4:00PM Anonymous (not verified) 8 February 2021 Online

 This event explores lessons and opportunities from conflict-affected states.

In the field of peacebuilding, scholars and policymakers increasingly recognize the importance of environmental restoration, afforestation and infrastructural renewal for creating the sustainable livelihoods necessary for successful peacebuilding efforts.

Featuring academics writing for International Affairs on environmental peacebuilding in Colombia, Yemen and the Sahel, this webinar discusses the policy implications of the turn to environmental peacebuilding.

This event is part of the Chatham House’s Environment and Society Discussion Series in which the Energy Environment and Resources Programme brings together leading academics and policymakers to discuss key issues in environmental policy.

In particular, this event focuses on the role of environmental peacebuilding in creating sustainable livelihoods. From the impact the destruction of infrastructure can have on poverty as a driver of conflict, to the role environmental peacebuilding can play in bringing communities together by creating sustainable shared spaces of employment, the importance of the environmental livelihood creation is difficult to overstate.

Panellists focus on how policymakers can best encourage inclusive and sustainable livelihood creation and on addressing the key challenges such approaches face in the context of environmental peacebuilding efforts.

Youth voices on climate action 22 April 2021 — 12:30PM TO 2:00PM Anonymous (not verified) 22 March 2021 Online

To celebrate Earth Day, youth activists, local change-makers, innovators and entrepreneurs discuss opportunities and challenges for youth-led climate activism.

Young people will bear the brunt of the intensifying impacts of climate change over time. Facing this challenge, youth around the world have emerged at the forefront of climate activism at an unprecedented scale.

School strikes, marches, and declarations complement youth engagement in diplomacy, technology, science, and law. Providing a platform for young people involved in climate action at the local, national and global levels is essential to promote collaboration, generate new policy ideas, and demand accountability from political and business leaders.

Panellists engage in critical conversation about COP26; global leadership in climate mitigation, adaptation, and finance; and how to develop the full potential of youth-led global initiatives going forward.

Prioritizing equity and justice in climate action 30 June 2021 — 11:00AM TO 12:00PM Anonymous (not verified) 10 June 2021 Online

London Climate Action Week event: Why understanding equity and justice is essential to the ability to meaningfully inform climate politics.

Citizen-led climate activism is demonstrating the need to think about climate change ‘not just as a problem for science to solve’ but also as a problem of equity, human rights and justice.

The disproportionate impacts of climate change on the poor and the marginalized across the world means that understanding equity and justice is essential for the ability to meaningfully inform climate politics.

Excluding these issues risks ignoring, or intentionally omitting, the consequences of policies, tools and frameworks on those who are most likely to face the severe costs of any climate action or inaction.

In a pivotal year for climate decision-making, this event explores the necessity of equity and justice in climate action and how the world can move the political conversation to one that is more inclusive.

The speakers explore how communities themselves articulate the justice dimensions of climate change and how fairness can create a greener future for current and future generations.

This event is being hosted as a part of Strengthening Climate Diplomacy, a series of events from Chatham House during London Climate Action Week 2021.

COVID-19 and food security in southern Africa 16 July 2021 — 10:00AM TO 11:30AM Anonymous (not verified) 10 June 2021 Online

This event aims to take a deeper look at the interlinking issues of food security, nutrition, climate change and food systems in southern Africa.

Developing climate smart agri-food systems in sub-Saharan Africa is a precondition for achieving the Sustainable Development Goals. Over the years household food security has been affected by different shocks including climate change and the recent COVID-19 pandemic.

The impact on rural households in southern Africa, in particular, has been significant due to the structure of food systems in the region.

This event aims to take a deeper look at the interlinking issues of food security, nutrition, climate change and food systems in southern Africa and consider how practitioners and policymakers can build more equitable, resilient and better food systems. 

What does sustainable agriculture mean? 24 May 2022 — 5:30PM TO 6:30PM Anonymous (not verified) 11 May 2022 Chatham House and Online

Experts compare and contrast visions of ‘sustainable’ agriculture.

There is growing and unprecedented recognition of the adverse effects of food systems on global warming, air and water pollution, biodiversity, soil, and managing the emergence and spread of infectious diseases. At the same time, concern is rising over the role of climate change itself in compromising food security, supply-chain resilience and food price spikes.

Against this backdrop, the need for agriculture to become more ‘sustainable’ is clear. However, there is little consensus over what that means in practice. To address this, Chatham House is launching a new research paper comparing and contrasting the two most commonly articulated versions of ‘sustainable agriculture’.

The first focuses on sparing land for nature and increasing the productivity of agricultural land while minimizing environmental impacts. The second involves scaling up nature-friendly farming while emphasizing demand-side changes to reduce the overall pressure on land.

• How can we understand the arguments in support of either version and the assumptions and ideologies which underpin them?

• What are the implications of promoting one version of agriculture over the other

• How can policy transform agriculture and food systems?

• What should civil society support as ‘sustainable’ choices?