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Histone recognition by “reader” modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as “K4me3-R8me2a” and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 “K4me3-K9me3/2” bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 “K4me3-K9me3” peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 “K4me3-K9me3/2” bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

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.

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.

V. G. Lysov
Trans. Moscow Math. Soc. 83 (), 291-304.
Abstract, references and article information

E. A. Rakhmanov and S. P. Suetin
Trans. Moscow Math. Soc. 83 (), 269-290.
Abstract, references and article information

A. I. Aptekarev and M. L. Yattselev
Trans. Moscow Math. Soc. 83 (), 251-268.
Abstract, references and article information

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

A. B. Bogatyrev
Trans. Moscow Math. Soc. 83 (), 217-225.
Abstract, references and article information

A. V. Domrina
Trans. Moscow Math. Soc. 83 (), 201-215.
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

Z. A. Kasumov and N. R. Akhmedzade
Trans. Moscow Math. Soc. 83 (), 67-74.
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

N. R. Ikonomov and S. P. Suetin
Trans. Moscow Math. Soc. 83 (), 33-54.
Abstract, references and article information

A. P. Starovoitov and N. V. Ryabchenko
Trans. Moscow Math. Soc. 83 (), 15-31.
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

Fossil Fuels Expert Roundtable: Forecasting Forum 2018 12 February 2018 — 2:00PM TO 5:30PM Anonymous (not verified) 18 December 2017 Chatham House, London

This forum will present the latest thinking from senior researchers on the dynamics that will affect fossil fuels investment and markets in the year ahead. The first session will assess the various factors keeping oil and gas prices from bouncing back and will consider conditions and political developments that could influence markets in the year ahead. The second session will assess the future of the power sector and what this means for the fossil fuels industry.

Attendance at this event is by invitation only.

Visualizing the Data: The Evolution of Trade Tensions in Metals and Minerals Markets 18 January 2018 — 4:30PM TO 6:00PM Anonymous (not verified) 19 December 2017 Chatham House, London

Over the past decade, producer countries such as South Africa, Zambia, Indonesia, the DRC and, most recently, Tanzania have restricted exports of unprocessed precious metals, copper, nickel, cobalt and other minerals in an attempt to support, or create, downstream processing industries and jobs or increase revenues. These moves have invariably created tensions with trading partners. Research suggests that export restrictions are not the best way to achieve such policy objectives and can instead harm the producer country’s economy and undermine the functioning of international metals and minerals.

Drawing on OECD and Chatham House research on resource trade, the speaker will present analysis and data visualizations exploring the drivers of past export restrictions and their political and economic impacts. They will also consider how the drivers of ‘resource nationalist measures’ are changing, whether and where export restrictions might present strategic and economic risks in the current context, and the extent to which producer and consumer governments and international governance mechanisms are prepared to address them.

Attendance at this event is by invitation only.

Fossil Fuels Expert Roundtable: How Solar is Shaping the Energy Transition 1 June 2018 — 9:00AM TO 10:30AM Anonymous (not verified) 22 May 2018 Chatham House, London

As global temperatures rise and extreme weather events multiply, doubts over the reality and imminence of climate change have dissipated. Despite this, there is a clear lack of urgency by governments to the approaching crisis. At this event, Prem Shankar Jha will set out what he believes are the three main causes for this inaction.

Furthermore, he will argue that catastrophic climate change is imminent, but even if it weren’t, the risk is too great to ignore. Only a complete shift from fossil fuels by 2070 at the latest would provide reasonable certainty of avoiding irreversible consequences. This transition is not only possible but the technologies to enable it were harnessed four to nine decades ago – and all of them draw their primary energy from the sun. These technologies are already capable of delivering electricity, transport fuels, and petrochemicals at prices that are competitive with the current delivered cost of electricity in the US and Western Europe. So what is holding up the energy shift?

Attendance at this event is by invitation only.

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.

Decarbonizing Heat: A New Frontier for Technologies and Business Models 27 February 2019 — 8:15AM TO 9:45AM Anonymous (not verified) 3 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Building space and water heating accounts for over 35 percent of global energy consumption - nearly double that of transport. However, there has been limited progress in decarbonizing the sector to date. International cooperation is required to ensure harmonized policies drag low carbon heating technologies down the cost curve to the extent that low carbon heating is cost competitive and affordable. The initial presentations and discussion focus on:

• Demand reduction technologies and policies that speed up transformation of the sector.
• The different challenges for energy efficiency of retrofitting as opposed to new build.
• The impact of electrification on GHG emissions and the power sector.
• The comparative role of national and city level initiatives.

The meeting concludes by looking at the challenges and risks in accelerating the transformation of heating and the lessons that can be learned from other sectors.

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.

The Impact of Brexit on Energy Transformation in the UK and EU 28 March 2019 — 8:15AM TO 9:45AM Anonymous (not verified) 3 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

The UK’s decision to leave the EU will fundamentally reshape many of the UK’s policies and its relations with countries around the world. For energy and climate, the changes could be significant and will need to be managed carefully to secure ongoing investment, stable energy prices and ambitious climate objectives. The UK’s departure will also affect the balance of political support for climate and energy policies with the EU institutions and potentially impact upon regional initiatives.

This roundtable will discuss:

• The impact on the energy sector of Brexit during the transition period through until December 2020 including the operation of interconnectors and access to the Internal energy market, ongoing engagement in European research collaboration and the replacement of European financial resources.
• The possible opportunities and risks for the UK’s energy sector in 2021 and beyond.
• The implications of Brexit on the EU’s energy and climate policy.

The roundtable will discuss the role of the public and business in shaping the future deal as it will need to be ratified by the parliaments of all member states.

Attendance at this event is by invitation only.