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Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2 [Signal Transduction]

The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the SHP2 gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography, and molecular modeling, as well as using cell biology approaches, here we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the WT enzyme, the interactions between its N-SH2 and protein-tyrosine phosphatase domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and a potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enable the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr-53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity.




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Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3 [Cell Biology]

Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.




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{alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease]

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.




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A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning [Molecular Biophysics]

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.




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Reactive dicarbonyl compounds cause Calcitonin Gene-Related Peptide release and synergize with inflammatory conditions in mouse skin and peritoneum [Molecular Bases of Disease]

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.




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Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy [Molecular Bases of Disease]

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.




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How the Soleimani Assassination Will Reverberate Throughout the Middle East

6 January 2020

Dr Sanam Vakil

Deputy Director and Senior Research Fellow, Middle East and North Africa Programme

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative

Dr Lina Khatib

Director, Middle East and North Africa Programme
Regional experts examine how Iran benefits from the fallout of the killing, the implications for politics in Iraq and how Tehran might respond with its proxies in the region.

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Protesters hold up an image of Qassem Soleimani during a demonstration in Tehran on 3 January. Photo: Getty Images.

An unexpected bounty for Iran

Sanam Vakil

The assassination of Qassem Soleimani has been an unexpected bounty for the Islamic Republic at a time when Iran was balancing multiple economic, domestic and regional pressures stemming from the Trump administration’s maximum pressure campaign.

Coming on the heels of anti-Iranian demonstrations in Iraq and Lebanon, and following Iran’s own November 2019 protests that resulted in a brutal government crackdown against its own people, the Soleimani killing has helped the Iranian government shift the narrative away from its perceived regional and domestic weaknesses to one of strength.  

The massive funeral scenes in multiple Iranian cities displaying unending waves of mourners chanting against the United States has provided the Islamic Republic with a unique opportunity to showcase its mobilizing potential. This potential is not limited to Iran but also extends to Iraq and Lebanon, where Tehran’s transnational summoning power has also been visible. The Iraqi parliamentary vote to end the American military presence is one early negative consequence. While the region awaits Iran’s response, further anti-American rallying cries will continue to reverberate.  

Domestically, Soleimani’s death and President Donald Trump’s continued provocations on Twitter, including threats to attack 52 Iranian cultural sites, are being used as a nationalist rallying cry. This sentiment should not be seen solely as Islamic or ideological, but rather an opportunity for the state to pivot to an Iranian-based nationalism that is more inclusive and empowering for much of the country’s disgruntled youth.

Iran’s notoriously divided political factions have also unified in the face of this crisis. With parliamentary elections looming in February and turnout previously expected to be low, the political establishment is likely to use this crisis to mobilize voters in favour of conservative candidates.  

How Tehran chooses to respond to Qassem Soleimani’s death will very much determine its ability to continue to control the narrative and manage its swell of domestic and regional support. For these benefits to continue to manifest, it is important for Tehran to balance the mix of public sympathy and international anxiety and not overplay its hand in its quest for revenge.

A reset for Iraqi politics

Renad Mansour

The US strike which killed Qassem Soleimani and Abu Mehdi al-Muhandis has grave implications for Iraq. The act jeopardizes Iraq’s recently stabilized security situation, and threatens to reshape the country’s political environment, moving backwards to the days of anti-Americanism and sect-based mobilization. If Baghdad loses relations with the US and other diplomatic representations, it risks turning into a pariah state. 

Over the past few years, and notably since October 2019, young Iraqis have taken to the streets demanding reform and the downfall of the political establishment, and its main external backer Iran. The political establishment, including political parties and militias close to Tehran, failed to appease or suppress these protests. Now, these political elites are using the deaths of Muhandis and Soleimani to (re)gain popularity from their own population, by drawing on the old tool of anti-Americanism. 

Following the attacks, Shia populist cleric Muqtada al-Sadr – who until recently had called for an end to Iranian and pro-Iranian militia influence in Iraq – has called to revamp the Mehdi Army that he led until 2008 and is calling for ‘Islamic resistance’ to the US. In seeking to regain control of his former movement, he is coming closer to former Shia foes.

For years, pro-Iranian groups attempted to push the US out of Iraq. Their calls often fell on deaf ears, as public opinion in Iraq did not consider the US as a threat and some even supported the US and international effort against ISIS. Following the attacks, however, anti-American voices have gained more ammunition.

A complete American withdrawal would not only have direct security implications but force other countries and organizations, from European states to NATO, to reconsider their positions and role.

Limited options for ‘revenge’ in the Levant

Lina Khatib

Iran’s use of Lebanon and Syria as spaces for revenge against the US is unlikely.

On Sunday, Hezbollah leader Hassan Nasrallah vowed revenge for Soleimani’s death by singling out American soldiers as a target. However, Hezbollah’s options are limited. Lebanon is in the middle of wide-ranging protests against the country’s ruling political class, of which Nasrallah is a key figure.

Unlike in 2006, when Hezbollah’s military actions against Israel rallied the public around it, today there is no public appetite for dragging Lebanon into a war. Were Hezbollah to instigate one, it would incur public anger, if only for the economic repercussions that would exacerbate an already severe financial crisis in Lebanon. Lebanon also does not have any US military bases that could be a target for Hezbollah.

In theory, Hezbollah or other Iranian-backed groups could attack American bases in Syria. But these bases are staffed by multinational forces from the international anti-ISIS coalition. Attacking them would therefore put Iran in confrontation with other countries besides the US, which is not in Iran’s interest.

Attacking US soldiers in northeast Syria would also go against Kurdish interests because it would weaken the anti-ISIS coalition front of which Kurdish forces are part. It would, furthermore, anger Arab tribes in the area, opening up possibilities for ISIS to take advantage of public dissent to stage a comeback. Iran would then find itself fighting on several fronts at once, which it does not have the capacity to handle. 

More likely, Iran’s allies and proxies in the Levant are going to engage in strong rhetoric without taking hasty actions. When a key Hezbollah leader, Imad Mughniyeh, was assassinated in Damascus on 2008, there were strong words and public vows to seek revenge for his killing, but ultimately there was no response.    




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Expanding Sino–Maghreb Relations: Morocco and Tunisia

26 February 2020

Over the past two decades, China has increased its presence in North Africa in terms of trade and investment. This paper looks at China’s policy within the context of its Africa and Middle East policies to better understand its approach to Morocco and Tunisia.

Yahia H. Zoubir

Senior Professor of International Studies, KEDGE Business School, France and Visiting Fellow, Brookings Doha Center

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Chinese President Xi Jinping and King Mohammed VI of Morocco wave during a welcoming ceremony outside the Great Hall of the People in Beijing on 11 May 2016. Photo: Getty Images.

Summary

  • China’s presence in the Maghreb has increased in recent years, raising concerns among Western powers. China has focused on bilateral relations with these countries while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF). However, this engagement has limited strategic value compared to relations China has with Saudi Arabia or the United Arab Emirates.
  • Since the launch of the Belt and Road Initiative (BRI) in 2013, China has shown greater interest in the Maghreb as an entry point to European and African markets. China has pursued commercial relations over political influence in the region. Morocco and Tunisia are still dependent on France, their former colonial power, and the European Union, which exert great political, economic, security and cultural influence over the two countries.
  • The Maghreb countries’ economic relations with China have grown exponentially, with Algeria forming the closest relationship. However, Morocco and Tunisia are keen to attract China’s investment and involvement in major construction and infrastructure projects to boost industrial and economic development. While China’s investments in Morocco and Tunisia remain at a low level, trade relations with both countries have grown steadily. Politically, China’s policy of noninterference in domestic affairs appeals to Maghreb states, which resent Western interference.
  • China’s influence in the Maghreb remains minimal. Its soft power push has struggled to promote advantages of strong relations with China beyond economics. Furthermore, Morocco and Tunisia’s populations have generally scant knowledge about China’s politics and culture. China has tried to address this lack of familiarity through the establishment of Confucius Institutes and other cultural activities. However, language and cultural barriers still impede the development of close relations, compared to those China has with other countries in Africa.




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POSTPONED: The Development of Libyan Armed Groups since 2014: Community Dynamics and Economic Interests

Invitation Only Research Event

18 March 2020 - 9:00am to 10:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Abdul Rahman Alageli, Associate Fellow, MENA Programme, Chatham House
Emaddedin Badi, Non-Resident Scholar, Middle East Institute
Tim Eaton, Senior Research Fellow, MENA Programme Chatham House
Valerie Stocker, Independent Researcher

Since the overthrow of the regime of Muammar Gaddafi in 2011, Libya’s multitude of armed groups have followed a range of paths. While many of these have gradually demobilized, others have remained active, and others have expanded their influence. In the west and south of the country,  armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks.

In the east, the Libyan Arab Armed Forces projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will need to address the fears, grievances and desires of the surrounding communities, even while the development of armed groups’ capacities dilutes their accountability to those communities.

This roundtable will discuss the findings of a forthcoming Chatham House research paper, ‘The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests’, which presents insights from over 200 interviews of armed actors and members of local communities and posits how international policymakers might seek to curtail the continued expansion of the conflict economy.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Event attributes

Chatham House Rule

Georgia Cooke

Project Manager, Middle East and North Africa Programme
+44 (0)20 7957 5740




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The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests

17 March 2020

This paper explores armed group–community relations in Libya and the sources of revenue that have allowed armed groups to grow in power and influence. It draws out the implications for policy and identifies options for mitigating conflict dynamics.

Tim Eaton

Senior Research Fellow, Middle East and North Africa Programme

Abdul Rahman Alageli

Associate Fellow, Middle East and North Africa Programme

Emadeddin Badi

Policy Leader Fellow, School of Transnational Governance, European University Institute

Mohamed Eljarh

Co-founder and CEO, Libya Outlook

Valerie Stocker

Researcher

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Fighters of the UN-backed Government of National Accord patrol in Ain Zara suburb in Tripoli, February 2020. Photo: Amru Salahuddien

Summary

  • Libya’s multitude of armed groups have followed a range of paths since the emergence of a national governance split in 2014. Many have gradually demobilized, others have remained active, and others have expanded their influence. However, the evolution of the Libyan security sector in this period remains relatively understudied. Prior to 2011, Libya’s internal sovereignty – including the monopoly on force and sole agency in international relations – had been personally vested in the figure of Muammar Gaddafi. After his death, these elements of sovereignty reverted to local communities, which created armed organizations to fill that central gap. National military and intelligence institutions that were intended to protect the Libyan state have remained weak, with their coherence undermined further by the post-2014 governance crisis and ongoing conflict. As a result, the most effective armed groups have remained localized in nature; the exception is the Libyan Arab Armed Forces (LAAF), which has combined and amalgamated locally legitimate forces under a central command.
  • In the west and south of the country, the result of these trends resembles a kind of inversion of security sector reform (SSR) and disarmament, demobilization and reintegration (DDR): the armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks; and have continued to arm, mobilize and integrate themselves into the state’s security apparatus without becoming subservient to it. In the eastern region, the LAAF projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. The LAAF has co-opted social organizations to dominate political and economic decision-making.
  • The LAAF has established a monopoly over the control of heavy weapons and the flow of arms in eastern Libya, and has built alliances with armed groups in the east. Armed groups in the south have been persuaded to join the LAAF’s newly established command structure. The LAAF’s offensive on the capital, which started in April 2019, represents a serious challenge to armed groups aligned with the Tripoli-based Government of National Accord (GNA). The fallout from the war will be a challenge to the GNA or any future government, as groups taking part in the war will expect to be rewarded. SSR is thus crucial in the short term: if the GNA offers financial and technical expertise and resources, plus legal cover, to armed groups under its leadership, it will increase the incentive for armed groups to be receptive to its plans for reform.
  • Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will necessarily rely on addressing the fears, grievances and desires of the surrounding communities. Yet the development of armed groups’ capacities, along with their increasing access to autonomous means of generating revenue, has steadily diluted their accountability to local communities. This process is likely to be accelerated by the ongoing violence around Tripoli.
  • Communities’ relationship to armed groups varies across different areas of the country, reflecting the social, political, economic and security environment:
  • Despite their clear preference for a more formal, state-controlled security sector, Tripoli’s residents broadly accept the need for    the presence of armed groups to provide security. The known engagement of the capital’s four main armed groups in criminal activity is a trade-off that many residents seem able to tolerate, providing that overt violence remains low. Nonetheless, there is a widespread view that the greed of Tripoli’s armed groups has played a role in stoking the current conflict.
  • In the east, many residents appear to accept (or even welcome) the LAAF’s expansion beyond the security realm, provided that it undertakes these roles effectively. That said, such is the extent of LAAF control that opposition to the alliance comes at a high price.
  • In the south, armed groups draw heavily on social legitimacy, acting as guardians of tribal zones of influence and defenders of their respective communities against outside threats, while also at times stoking local conflicts. Social protections continue to hold sway, meaning that accountability within communities is also limited.
  • To varying extents since 2014, Libya’s armed groups have developed networks that enmesh political and business stakeholders in revenue-generation models:
  • Armed groups in Tripoli have compensated for reduced financial receipts from state budgets by cultivating unofficial and illicit sources of income. They have also focused on infiltrating state institutions to ensure access to state budgets and contracts dispersed in the capital.
  • In the east of the country, the LAAF has developed a long-term strategy to dominate the security, political and economic spheres through the establishment of a quasi-legal basis for receiving funds from Libya’s rival state authorities. It has supplemented this with extensive intervention in the private sector. External patronage supports military operations, but also helps to keep this financial system, based on unsecured debt, afloat.
  • In the south, limited access to funds from the central state has spurred armed groups to become actively involved in the economy. This has translated into the taxation of movement and the imposition of protection fees, particularly on informal (and often illicit) activity.
  • Without real commitment from international policymakers to enforcing the arms embargo and protecting the economy from being weaponized, Libya will be consigned to sustained conflict, further fragmentation and potential economic collapse. Given the likely absence of a political settlement in the short term, international policymakers should seek to curtail the continued expansion of the conflict economy by reducing armed groups’ engagement in economic life.
  • In order to reduce illicit activities, international policymakers should develop their capacity to identify and target chokepoints along illicit supply chains, with a focus on restraining activities and actors in closest proximity to violence. Targeted sanctions against rent maximizers (both armed and unarmed) is likely to be the most effective strategy. More effective investigation and restraint of conflict economy actors will require systemic efforts to improve transparency and enhance the institutional capacity of anti-corruption authorities. International policymakers should also support the development of tailored alternative livelihoods that render conflict economy activities less attractive.




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COVID-19 and the Iranian Shadows of War

8 April 2020

Dr Sanam Vakil

Deputy Director and Senior Research Fellow, Middle East and North Africa Programme
Coronavirus has plunged Iran into the country’s biggest crisis since its war with Iraq. More than 30 years later, the lingering effects of the war are shaping Iran’s reaction to the pandemic.

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Spraying disinfectant at Tajrish bazaar in Tehran, Iran, during the coronavirus pandemic in March 2020. Photo by Majid Saeedi/Getty Images.

In the face of the COVID-19 pandemic, many global leaders have invoked war analogies – from the Pearl Harbor attack to the collective spirit on display during the Second World War – to highlight past lessons learned or rally their populations.

For Iran’s leadership, more recent war analogies hold resonance and help explain the ideological and political conundrum limiting an effective COVID-19 response. While the Islamic Republic has weathered a multitude of challenges, COVID-19 is putting unprecedented strain on Iran’s already fragile, heavily-sanctioned economy and further exposing domestic political fissures amid ongoing international tensions.

Iran has been identified as the regional epicentre of the pandemic with a steadily rising number of deaths, including several of the country’s political and military elite. Yet the Iranian government has not evoked the collective memory of the war as an opportunity for national resistance and mobilization.

Sluggish and poorly managed

This is unsurprising, because thus far the Iranian government’s response to COVID-19 has been sluggish and poorly managed. After an initial slow response, Iran then attempted to downplay the impact of the virus, covering up the number of cases and deaths and blaming the United States, before implementing a poorly coordinated action plan marred by government infighting.

For the Iranian leadership, the Iran-Iraq war has been the single most influential and defining period – it has impacted its political ideology, domestic and security policies and international relations. More than half a million Iranians died, and a paranoid worldview and sense of isolation was cemented among many elite leaders such as Supreme Leader Ali Khamenei.

The war created a valiant culture of leadership from Qassem Soleimani to presidents Mahmoud Ahmadinejad and Hashemi Rafsanjani and, over time, has resulted in the development of Iran’s asymmetrical defense capabilities.

The war enabled a dark purge of political opponents and the gradual birth of Iran’s reformist faction, all while the ethos of sacrifice and martyrdom was linked to the collective notions of resistance.

These would be carried forward in other resistance campaigns both regional and economic. Most defining was Ayatollah Khomeini’s infamous 1988 decision to ‘drink the poisoned chalice’ and end the long war. Three decades later, Iran continues to contend with those outcomes.

To acknowledge that the COVID-19 crisis could have equally profound consequences would add further pressure to the Islamic Republic at a time of incomparable vulnerability. Even before this crisis, the Iranian government linked sanctions to economic warfare, making future negotiations conditional on sanctions relief.

Iranian hardliners used the opportunity to promote Iran’s subsistence-based resistance economy designed to insulate Iran’s economy from external shocks such as sanctions. While both groups recognize the economic urgency, their contending strategies help explain the muddled government response and the ongoing ideological competition between the political elites.

Rouhani has argued that a full lockdown of the Iranian economy is impossible because it is already under significant strain from sanctions - the Iranian economy experienced a 9.5% contraction in 2019 and is expected to worsen in the coming year.

That said, through Iran’s New Year holidays the government did take action to slow the spread of the virus, discouraging travel and shutting schools, pilgrimage sites and cancelling Friday prayers. Finally, on 4 April, after receiving permission from Khamenei to do so, Rouhani withdrew $1 billion from Iran’s National Development Fund and is distributing the money through loans and credits to 23 million households.

Aid from a number of Iran’s parastatal agencies was also announced. Conversely, in his annual New Year’s speech the supreme leader securitized the crisis by laying blame on the United States for spreading the virus as a form of biological terrorism. Iran’s army chief of staff Major General Bagheri was tasked with building hospitals and the Islamic Revolution Guard Corps given authority to clear the streets.

The recent expulsion of Médecins Sans Frontières from Iran highlights the mix of paranoia and resistance culture still on display. US sanctions on Iran have significantly weakened Iran’s economy and limited Tehran’s ability to purchase much needed medical supplies and equipment. Unable to access its foreign reserves due to sanctions, the Rouhani government has applied for a $5 billion loan from the IMF.

European countries alongside a number of US members of congress have appealed to the Trump administration to ease sanctions on humanitarian grounds. While Washington continues to pursue its steadfast approach, referring to Iran’s campaign as a ‘sanctions relief scam’, Germany, France, and the UK have offered $5 million in aid and launched INSTEX – a trading mechanism designed to circumvent sanctions to allow non-sanctioned humanitarian trade.

The impact of coronavirus on Iranian society remains to be seen. But the impact of sanctions has placed heavy economic and psychological burden on the people. Feeling abandoned by the Iranian state and the United States could produce a mix of contradictory nationalistic and independent impulses.

The social contract – already fragile amid protests and government repression – reveals declining trust. Without national mobilization and calls for unity reminiscent of the war period, Iranians have stepped in, highlighting the continued resilience of civil society. Support for the medical establishment has been celebrated throughout the country and on social media. Charities, the private sector - through one initiative known as Campaign Nafas (Breathe) - and diaspora groups have initiated fundraising drives and assistance measures.

Iran’s relations with the international community, and specifically the United States, remain an unresolved consequence of the war. The 2015 Iranian nuclear agreement was the closest Tehran and Washington came to resolving decades of tensions, containment and sanctions.

COVID-19 has further heightened the trajectory of tensions between Tehran and Washington suggesting that any new deal, while necessary, is not on the cards. Tit-for-tat military exchanges have been on the rise in Iraq and Yemen while American and Iranian leaders issue threats and warnings of potential escalation.

Abdullah Nasseri, an advisor to Iran’s reformists, recently stated that in order to manage the coronavirus crisis, the Iranian government needed to make a decision akin to the 1988 United Nations resolution 598 that ended war hostilities. Ayatollah Khomeini famously commented on that ceasefire, stating: ‘Happy are those who have departed through martyrdom. Unhappy am I that I still survive.… Taking this decision is more deadly than drinking from a poisoned chalice. I submitted myself to Allah's will and took this drink for His satisfaction’. 

While a similar compromise today might appear deadly to the political establishment, it is clear that a paradigm shift away from the shadows of Iran’s last war is urgently needed to manage the challenges stemming from COVID-19.




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Webinar: Reimagining the Role of State and Non-State Actors in (Re)building National Health Systems in the Arab World

Research Event

22 April 2020 - 1:00pm to 2:00pm

Event participants

Fadi El-Jardali, Professor of Health Policy and Systems, American University of Beirut
Moderator: Nadim Houry, Executive Director, Arab Reform Initiative

As new cases of COVID-19 continue to surge, countries around the world struggle to mitigate the public health and economic effects of the virus. It is becoming increasingly clear that an effective pandemic response requires a whole-of-government, whole-of-society approach. In the Arab world, where health systems are already strained by armed conflicts and displaced populations, a whole-of-society response to the pandemic is particularly critical as countries have become increasingly dependent on non-state actors, notably the private sector, for healthcare provision and any response that includes the state alone may not be sufficient to address the pandemic.

In a recent article, Fadi El-Jardali, argued that while the pandemic will have grave health and economic consequences for years to come, it brings with it a valuable opportunity to re-envision the role of state and non-state actors in strengthening health systems. The article addressed the need for increased collaboration between state and non-state actors, and the rethinking of existing cooperation models to provide quality healthcare services for all.  

In this webinar, part of the Chatham House project on the future of the state in the Middle East and North Africa, Dr El-Jardali will discuss how state and non-state actors can collaborate more effectively to address the shortcomings of national health care systems amidst the pandemic and beyond. The article’s author will share insights on the different capacities available in Arab societies that governments can draw upon to ensure that Universal Health Coverage, equity considerations and social justice are at the core of health systems.

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

 

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Can Protest Movements in the MENA Region Turn COVID-19 Into an Opportunity for Change?

29 April 2020

Dr Georges Fahmi

Associate Fellow, Middle East and North Africa Programme
The COVID-19 pandemic will not in itself result in political change in the MENA region, that depends on the ability of both governments and protest movements to capitalize on this moment. After all, crises do not change the world - people do.

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An aerial view shows the Lebanese capital Beirut's Martyrs Square that was until recent months the gathering place of anti-government demonstrators, almost deserted during the novel coronavirus crisis, on 26 March 2020. Photo by -/AFP via Getty Images.

COVID-19 has offered regimes in the region the opportunity to end popular protest. The squares of Algiers, Baghdad, and Beirut – all packed with protesters over the past few months – are now empty due to the pandemic, and political gatherings have also been suspended. In Algeria, Iraq and Lebanon, COVID-19 has achieved what snipers, pro-regime propaganda, and even the economic crisis, could not.

Moreover, political regimes have taken advantage of the crisis to expand their control over the political sphere by arresting their opponents, such as in Algeria where the authorities have cracked down on a number of active voices of the Hirak movement. Similarly, in Lebanon, security forces have used the pandemic as an excuse to crush sit-ins held in Martyr’s Square in Beirut and Nour Square in Tripoli.

However, despite the challenges that the pandemic has brought, it also offers opportunities for protest movements in the region. While the crisis has put an end to popular mobilization in the streets, it has  created new forms of activism in the shape of solidarity initiatives to help those affected by its consequences.

In Iraq, for example, protest groups have directed their work towards awareness-raising and sharing essential food to help mitigate the problem of food shortages and rising prices across the country. In Algeria, Hirak activists have run online campaigns to raise awareness about the virus and have encouraged people to stay at home. Others have been cleaning and disinfecting public spaces. These initiatives increase the legitimacy of the protest movement, and if coupled with political messages, could offer these movements an important chance to expand their base of popular support.

Exposes economic vulnerability

Economic grievances, corruption and poor provision of public services have been among the main concerns of this recent wave of protests. This pandemic only further exposes the levels of economic vulnerability in the region. COVID-19 is laying bare the socio-economic inequalities in MENA countries; this is particularly evident in the numbers of people engaged in the informal economy with no access to social security, including health insurance and pensions.

Informal employment, approximately calculated by the share of the labour force not contributing to social security, is estimated to amount to 65.5% of total employment in Lebanon, 64.4% in Iraq, and 63.3% in Algeria. The crisis has underscored the vulnerability of this large percentage of the labour force who have been unable to afford the economic repercussions of following state orders to stay at home.

The situation has also called attention to the vital need for efficient public services and healthcare systems. According to the fifth wave of the Arab Barometer, 74.4% of people in Lebanon are dissatisfied with their country’s healthcare services, as are 67.8% of people in Algeria and 66.5% in Iraq.

Meanwhile, 66.2% of people in Lebanon believe it is necessary to pay a bribe in order to receive better healthcare, as do 56.2% of people in Iraq and 55.9% in Algeria. The COVID-19 crisis has highlighted the need for more government investment in public healthcare systems to render them more efficient and less corrupt, strengthening the protesters’ case for the need for radical socio-economic reforms.

On the geopolitical level, the crisis puts into question the stability-focused approach of Western powers towards the region. For years, Western powers have directed their aid towards security forces in the interests of combating terrorism but COVID-19 has proved itself to be a much more lethal challenge to both the region and the West.

Facing this new challenge requires international actors to reconsider their approach to include supporting health and education initiatives, as well as freedom of expression and transparency. As argued by Western policymakers themselves, it was China’s lack of transparency and slow response that enabled the proliferation of the virus, when it could have been contained in Wuhan back in December 2019.

This crisis therefore offers regional protest movements the opportunity to capitalize on this moment and push back against the policies of Western powers that have invested in regional stability only to the extent of combating Islamic jihad. 

But crises do not change the world, people do. The COVID-19 pandemic will not in itself result in political change in the MENA region. Rather, it brings opportunities and risks that, when exploited, will allow political actors to advance their own agendas. While the crisis has put an end to popular mobilization and allowed regimes to tighten their grip over the political sphere, behind these challenges lie real opportunities for protest movements.

The current situation represents a possibility for them to expand their popular base through solidarity initiatives and has exposed more widely the importance of addressing socio-economic inequalities. Finally, it offers the chance to challenge the stability-focused approach of Western powers towards the region which until now has predominantly focused on combating terrorism.




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The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus [Gene Regulation]

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.




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Substrate recognition and ATPase activity of the E. coli cysteine/cystine ABC transporter YecSC-FliY [Microbiology]

Sulfur is essential for biological processes such as amino acid biogenesis, iron–sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer–substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine–bound FliY, and maximally by l-cysteine– or l-cystine–bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family.




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NAD+ biosynthesis in bacteria is controlled by global carbon/nitrogen levels via PII signaling [Microbiology]

NAD+ is a central metabolite participating in core metabolic redox reactions. The prokaryotic NAD synthetase enzyme NadE catalyzes the last step of NAD+ biosynthesis, converting nicotinic acid adenine dinucleotide (NaAD) to NAD+. Some members of the NadE family use l-glutamine as a nitrogen donor and are named NadEGln. Previous gene neighborhood analysis has indicated that the bacterial nadE gene is frequently clustered with the gene encoding the regulatory signal transduction protein PII, suggesting a functional relationship between these proteins in response to the nutritional status and the carbon/nitrogen ratio of the bacterial cell. Here, using affinity chromatography, bioinformatics analyses, NAD synthetase activity, and biolayer interferometry assays, we show that PII and NadEGln physically interact in vitro, that this complex relieves NadEGln negative feedback inhibition by NAD+. This mechanism is conserved in distantly related bacteria. Of note, the PII protein allosteric effector and cellular nitrogen level indicator 2-oxoglutarate (2-OG) inhibited the formation of the PII-NadEGln complex within a physiological range. These results indicate an interplay between the levels of ATP, ADP, 2-OG, PII-sensed glutamine, and NAD+, representing a metabolic hub that may balance the levels of core nitrogen and carbon metabolites. Our findings support the notion that PII proteins act as a dissociable regulatory subunit of NadEGln, thereby enabling the control of NAD+ biosynthesis according to the nutritional status of the bacterial cell.




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The major subunit of widespread competence pili exhibits a novel and conserved type IV pilin fold [Protein Structure and Folding]

Type IV filaments (T4F), which are helical assemblies of type IV pilins, constitute a superfamily of filamentous nanomachines virtually ubiquitous in prokaryotes that mediate a wide variety of functions. The competence (Com) pilus is a widespread T4F, mediating DNA uptake (the first step in natural transformation) in bacteria with one membrane (monoderms), an important mechanism of horizontal gene transfer. Here, we report the results of genomic, phylogenetic, and structural analyses of ComGC, the major pilin subunit of Com pili. By performing a global comparative analysis, we show that Com pili genes are virtually ubiquitous in Bacilli, a major monoderm class of Firmicutes. This also revealed that ComGC displays extensive sequence conservation, defining a monophyletic group among type IV pilins. We further report ComGC solution structures from two naturally competent human pathogens, Streptococcus sanguinis (ComGCSS) and Streptococcus pneumoniae (ComGCSP), revealing that this pilin displays extensive structural conservation. Strikingly, ComGCSS and ComGCSP exhibit a novel type IV pilin fold that is purely helical. Results from homology modeling analyses suggest that the unusual structure of ComGC is compatible with helical filament assembly. Because ComGC displays such a widespread distribution, these results have implications for hundreds of monoderm species.




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Significant political change is coming to the Gulf

19 February 2015

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Photo by ArabianEye / Getty Images

Significant political change is coming to the Gulf monarchies, often seen in the West as bastions of stability, argues a new Chatham House report entitled Future Trends in the Gulf.

The Gulf states are already undergoing dramatic demographic and economic changes – changes which are being accelerated by lower oil prices.

The current political systems in the Gulf have been defined by the oil era, enabling governments to provide extensive economic benefits and no taxation, while maintaining a monopoly over political power. As the economic role of the state changes, its political role will change too.

Even at a time of plenty, pressures for political change have been rising. Significant changes in the availability of information, the surge in social media and women’s education are driving new demands for transparency.

Political protests have been most visible in Bahrain, but calls for change and reform have been growing in all of the Gulf countries. Raif Badawi, the blogger recently flogged in Saudi Arabia, is hardly an isolated case: campaigners for constitutional monarchies and elected parliaments have been facing severe punishments for years. 

The report author, Jane Kinninmont, says:

'The US and UK underestimate the significant leverage that they still have in the Gulf compared with most other countries, even if it is less than in the 20th century. As much as Asian countries are strengthening their trade links with the Gulf, they are reluctant to step forward as the security allies that the Gulf countries need.' 

Combating instability, extremism and sectarianism in the wider region requires looking hard at the pressures for change and insecurities inside the Gulf states. These help explain, for instance, why Qatar and the UAE have backed different sides in the intensifying civil conflict in Egypt.

The report, based on three years of research, argues that:      

  • It is time for the GCC countries to seize the opportunity to carry out gradual and consensual political and social reforms towards more constitutional forms of monarchy. 

  • Western countries, especially the US and UK, need to diversify the base of relations with the Gulf beyond the existing elite – and reach out to a broader base among the increasingly well-educated and aspirational new generation.

  • Defence cooperation with the Gulf needs to be placed in a wider political context, where respect for human rights is not seen as being at odds with security imperatives, but as part of ensuring sustainable security. The UK and US policy of expanding their military bases in Bahrain has sent a strong signal that political reform is not their priority. 

  • A fresh discourse on Gulf security needs to take account of the need for people to feel secure vis-à-vis their own governments, for instance by ensuring the police are held accountable by independent judiciaries, and ending lengthy detention without trial.

  • In partnering with Gulf countries against extremism, Western allies need to broach sensitive issues such as religious education in Saudi Arabia, or the impact on Western publics and Muslim communities outside the region of flogging a blogger for insulting Islam.

Editor's notes

Read the report Future Trends in the Gulf by Jane Kinninmont, MENA Programme. Embargoed until Thursday 19 February, 00:01 GMT. Read the executive summary here

When linking to this report, please use this link, which will go live when the embargo is lifted. 

This report will be launched at an event at Chatham House on 19 February.          

For all enquiries, please contact the press office. 

To contact the author directly, please use:
Email:  jkinninmont@chathamhouse.org
Phone: +44 (0)7967 325 993
Twitter: @janekinninmont




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Eliza Manningham-Buller Appointed as Co-President of Chatham House

22 July 2015

Eliza Manningham-Buller is confirmed as a president of Chatham House replacing Paddy Ashdown who steps down after 10 years.

The appointment of Baroness Manningham-Buller as a president of Chatham House was confirmed at the institute’s annual general meeting on Tuesday 21 July. Baroness Manningham-Buller joins Sir John Major and Baroness Scotland of Asthal as a co-president and succeeds Lord Ashdown of Norton-sub-Hamdon who has stepped down from the role after two terms.

Eliza Manningham-Buller was director-general of the UK Security Service (MI5) between 2002 and 2007 and became an independent life peer in 2008. She served as Chairman of Imperial College London from 2011 to 2015. She brings to Chatham House an extensive knowledge of and experience in international security as well as a deep interest in medical research and global health, having served as a member of the Board of Governors of the Wellcome Trust since 2008. In October 2015, Baroness Mannigham-Buller will become Chairman of the Trust’s Board of Governors.

Paddy Ashdown steps down after serving as a president for 10 years alongside Sir John Major, Patricia Scotland and their predecessors Lord Hurd of Westwell and Lord Robertson of Port Ellen, respectively. Over that period, the institute benefitted enormously from his extensive experience in international politics and conflict resolution, including as High Representative for Bosnia and Herzegovina from 2002 to 2006.

Dr Robin Niblett, director of Chatham House, said:

'I am delighted to welcome Elizabeth Manningham-Buller as a president of Chatham House. Throughout her career, she has brought deep knowledge, careful analysis and sound judgement to bear upon some of the most difficult dimensions of public policy. The institute will benefit greatly from these qualities as it draws on her engagement with Chatham House over the coming years.

I would like to pay tribute to Paddy Ashdown for his long-standing support of Chatham House. His contributions to our substantive debates, both internally and externally, have been invaluable on numerous occasions, and we look forward to his continued involvement with the institute as a member of our Panel of Senior Advisers.'

Baroness Manningham-Buller said:

“I am delighted to be elected as a Chatham House president at this important time in the institute’s history, as it grapples with a complex and inter-connected agenda of policy challenges. I look forward to working with John Major and Patricia Scotland in supporting Chatham House and its valuable and necessary work.

Editor's notes

A president’s term at Chatham House is for five years, renewable once. There are no governance responsibilities, which reside solely with the institute’s Council.

Chatham House’s three presidents underpin the institute’s independent, non-partisan voice on international affairs. The presidents confirm, through their experiences at the highest levels of government and diplomacy, the connection between Chatham House and policy-makers.




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First ever global analysis of refugees’ energy use: High costs and poor supply undermine humanitarian assistance

11 November 2015

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A migrant girl looks at a light illuminating a camp site of refugees and migrants on the Greek island of Lesbos, 4 October 2015. Photo: Getty Images.

About 90 per cent of refugees living in camps have no access to electricity and many lack any form of lighting at night, says a Chatham House report for the Moving Energy Initiative. Energy poverty in refugee settlements is not on the radar of international initiatives and humanitarian agencies are ill-equipped to deal with the scale of need. 

Heat Light and Power for Refugees: Saving Lives, Reducing Costs zooms in on the energy needs of refugees and displaced people worldwide, and presents the first ever estimates of the volume and costs of what they use.

'The problem goes beyond electricity. 80 per cent of those in camps rely on firewood for cooking and, as a result, we estimate that some 20,000 people die prematurely each year due to the pollution from indoor fires. Exposure to extremes of cold and heat are also killers for people living in flimsy, temporary shelter,' says Glada Lahn, senior research fellow at Chatham House. 'The current lack of provision for energy undermines the fundamental aims of humanitarian assistance,' she adds.

There are nearly 60 million forcibly displaced people in the world, and they pay staggering costs for energy. The 83,277 households living in Dadaab in Kenya, the world’s largest refugee settlement, spent an estimated $6.2 million on firewood last year, which accounts for approximately 24 per cent of their overall household income. (The average UK household spent 4 per cent of its income on energy in 2011.) In Uganda, almost half of refugee households surveyed by the UNHCR skip meals because they do not have enough fuel to cook with.

'The imperative is to find humane, creative and cost-effective ways to respond to the needs of so many individuals, most of whom are women and children.  Improving access to clean, safe and sustainable energy offers a promising way forward,' says Kofi Annan in the report’s foreword.

The report calls for an overhaul in the way that heat, light and power are delivered in humanitarian crises. It makes the case for new partnerships between humanitarian agencies and private providers to increase clean energy access in refugee settlements. Investment in energy infrastructure will also benefit host communities in some of the world’s poorest countries.

'As refugee households spend approximately $2.1 billion on energy each year, developing local markets for energy services could be part of a mix of solutions,' adds Lahn. 'Using green, culturally appropriate technologies could save lives, reduce CO2 emissions by 11 million tonnes per year and radically improve living standards. Introducing even the most basic solutions, such as improved cookstoves and basic solar lanterns, could save $323 million a year in fuel costs.' 

Other findings include:

  • Rape and violence against women is common in many unlit camps. Only 4 per cent of women and girls in households in the Goudoubo camp in Burkina Faso would go out after dark due to the lack of streetlights.
  • Wood equalling around 49,000 football pitches worth of forest (64,700 acres) is burned by displaced families living in camps each year, mainly in countries suffering severe deforestation, because they have no alternative sources of energy.
  • Firewood consumption emits nearly twice as much CO2 as liquid petroleum gas and produces little energy in comparison to its carbon intensity.

International Development Minister Grant Shapps said:

‘Across sub-Saharan Africa, hundreds of millions of people still do not have access to electricity. Women and girls are at risk of violence after dark, families are forced to inhale toxic kerosene fumes, and energy remains unaffordable for many.

‘With the technology in place and investors coming on board, the time to act is now. The UK's Energy Africa campaign is already kick-starting a solar revolution across the continent.

‘Supporting the Moving Energy Initiative is another way Britain can help boost access to clean, reliable and affordable energy. This will transform people’s lives and help achieve the UN’s goal of universal energy access by 2030.’

Editor's notes

  • Read Heat Light and Power for Refugees: Saving Lives, Reducing Costs by Glada Lahn and Owen Grafham.
  • To link back to the report in an article, please use this landing page for the final report.
  • The Moving Energy Initiative (MEI) is a collaboration between GVEP International, Chatham House, Practical Action Consulting, the Norwegian Refugee Council (NRC) and the United Nations High Commissioner for Refugees (UNHCR). The report is supported by the UK Department for International Development through the Humanitarian Innovation and Evidence Programme.
  • The number of refugee households in Dadaab, Kenya is as of May 2015.
  • Chatham House will host a press briefing with MEI programme board member Michael Keating and authors Glada Lahn and Owen Grafham on Thursday 12 November at 10:30-11:30 GMT. To register, or for interview requests, please contact the press office.
  • All figures are original and based on estimations and calculations prepared for the Moving Energy Initiative. Chatham House designed a model offering the first estimates of the scale and cost of energy use and CO2 emissions among forcibly displaced households worldwide, not including people affected by natural disasters. For more details on the populations considered in the report and used in the model, contact the authors.
  • The authors are available to answer questions from the media. Please contact the press office.

Contacts

Press Office

+44 (0)20 7957 5739




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By enabling formal trade, Nigeria can unleash its vast potential

3 December 2015

Nigeria’s booming informal trade is costly for society, business and government, yet a critical opportunity exists to formalize such trade and drive more sustainable and less volatile growth, argues a new report from Chatham House.

According to one estimate, informal activity accounts for up to 64 per cent of Nigeria’s GDP. Nigeria's Booming Borders: The Drivers and Consequences of Unrecorded Trade finds that this is a result of obstacles that impede trading through formal channels. These drivers include bureaucratic burdens and other factors, such as:

  • The need for Nigerian businesses to produce at least nine documents in order to send an export shipment and at least 13 in order to bring in an import consignment.
  • Rigid and dysfunctional foreign-exchange regulations that push most smaller traders into the incompletely regulated parallel exchange market.
  • Corruption and unofficial ‘taxation’, especially on major border highways, which delegitimize formal channels and encourage the use of smuggling routes.

As a result, the state loses direct tax revenues that would be generated by formal cross-border trade. This is not just siphoned into the informal economy; some is lost entirely. For example, many shippers opt to dock in neighbouring countries rather than deal with the expense and difficulty of using Nigeria’s ports.

Informal trade also undermines the social contract between the private sector and government. The state lacks tax revenues to pay its officials, improve infrastructure or implement reforms, while traders feel the government provides no services in return for any taxes they might pay.

‘Every day tens of thousands of unofficial payments are made, none destined for the government. Policy-makers need to create an environment that encourages trade to flow through formal channels and capture lost revenue’, says co-author Leena Koni Hoffmann.

‘Formalization would assist Nigeria to pursue more high-quality, high-tech economic activity at a time when rising labour costs in Asia are creating scope for Nigerian manufacturers to compete’, she adds.

The report makes a number of recommendations for how Nigeria could encourage more formal trade, including:

  • Strengthening the resources and capacity of the Federal Ministry of Industry, Trade and Investment to coordinate action across key government ministries, departments and agencies, as well as public and private stakeholders.
  • Prioritizing engagement in the development of Economic Community of West African States (ECOWAS) trade policies and fully implementing the ECOWAS Protocol on Free Movement of Persons to reduce harassment at borders.
  • Allowing banks to operate simple services for small and medium-sized businesses to make trade payments directly from Nigerian naira to CFA francs and vice versa.
  • Improving basic facilities that support traders, including improving the efficiency of border posts, installing truck parks and all-weather surfacing on market access roads, and introducing online booking for trucks to enter ports.
  • Separating responsibilities for assessing duty and tariff liabilities from revenue collection in order to reduce opportunities for corruption, an approach already tested with success by the Lagos State Internal Revenue Service.
  • Increasing funding and technical support for the National Bureau of Statistics, which has a significant role to play in measuring and capturing more of Nigeria’s external trade.

Interviews conducted for the report reveal that business people would welcome the opportunity to pay taxes, but only if they received assurance that these payments would represent a contract with government guaranteeing that conditions for business would be improved.

‘As Africa’s largest economy, formalizing external trade would allow Nigeria to fulfil its potential as the trading engine of the West and Central African economy and shape the business landscape across the region,’ says co-author Paul Melly.

Editor's notes

  • Read Nigeria's Booming Borders: the Drivers and Consequences of Unrecorded Trade (embargoed until 17:00 GMT on Monday 7 December).
  • To request an interview with the authors, contact the press office.
  • Nigeria’s recorded external trade for 2014 was $135.8 billion.
  • Estimate of informal activity as a percentage of GDP from Jonathan Emenike Ogbuabor and Victor A. Malaolu, ‘Size and Causes of the Informal Sector of the Nigerian Economy: Evidence from Error Correction Mimic Model’, Journal of Economics and Sustainable Development, Vol. 4, No. 1, 2013.

Contacts

Press Office

+44 (0)20 7957 5739




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Stavros Niarchos Foundation makes £3m grant for expansion at Chatham House

18 December 2015

The Royal Institute of International Affairs is pleased to announce a Cornerstone Contribution of £3m by the Stavros Niarchos Foundation (SNF) towards the Chatham House Second Century Initiative to support the expansion and renovation of the institute’s ground floor.

Following the institute’s purchase of the ground floor of the adjoining building (Ames House) in 2013, this generous grant from SNF will enable Chatham House to occupy this space and undertake a significant renovation project to create the ‘Stavros Niarchos Foundation Floor’ at Chatham House.

This will help the institute meet the growing demand for its research and analysis and take full advantage of its location in central London, given the city’s exceptional international connectivity and status as a global hub.

The SNF Floor will contain state-of-the-art meeting facilities for the institute’s research staff and fellows of the Queen Elizabeth II Academy for Leadership in International Affairs, and will significantly enhance the institute’s convening and communication capacities. To this end, the renovated space will include a ‘simulation room’, the Asfari Centre and a media room, as well as new breakout and meeting areas. The SNF Floor will be directly accessible from the ground floor of 10 St James’s Square, the institute’s main building.

The SNF grant is an important step forward for the institute’s Second Century Initiative which aims to ensure the institute’s long-term financial independence. The initiative has three principal targets:

● to endow a number of Research Fellowships and interdisciplinary Research Centres;

● to secure endowments to support the Queen Elizabeth II Academy for Leadership in International Affairs in order to nurture independent thinking on international policy among a new generation from around the world; and

● to secure the necessary physical space and infrastructure here in London to meet the growing demand for and scope of the institute’s work.

Dr Robin Niblett, director of Chatham House said: ‘We are enormously grateful to the Stavros Niarchos Foundation for this transformational grant which will significantly enhance Chatham House’s capacity to serve as a trusted and creative space for addressing the most important challenges in international affairs.’

Andreas Dracopoulos, co-president of SNF’s board of directors, said: ‘We are delighted to support the growth of Chatham House, one of Europe’s leading independent, non partisan policy institutes, at a time when the risks to global prosperity and stability are expanding. Chatham House’s reputation for providing world-leading analysis needs to remain as strong as ever and I am confident that this grant will help the institute take its research and convening activities in new interactive and interdisciplinary directions.

Editor's notes

Chatham House launched its Second Century Initiative in November 2014 as part of its preparations for its centenary in 2020. The Initiative aims to help secure the institute’s financial base and independence by strengthening its capacity to innovate in an increasingly competitive field of thought leadership and policy ideas. Renovation work on the ground floor of Ames House is expected to begin in the spring of 2016.

The Stavros Niarchos Foundation is one of the world’s leading international philanthropic organizations, making grants in the areas of arts and culture, education, health, medicine and sports, and social welfare. The Foundation funds organizations and projects that exhibit strong leadership and sound management and are expected to achieve a broad, lasting and positive impact for society at large. The Foundation also seeks actively to support projects that facilitate the formation of public-private partnerships as an effective means for serving public welfare.




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Centre on Global Health Security collaborates with the Gates Foundation at the Munich Security Conference

22 February 2016

Support from the Bill & Melinda Gates Foundation has enabled Chatham House to develop a global health security track at the Munich Security Conference (MSC).

The primary objectives of this three-year partnership are to integrate consideration of global health security challenges into the MSC agenda, highlight the threats from infectious diseases and stimulate discussion of the importance of investment in global health, particularly in low- and middle-income countries. 

At the 2016 MSC, the Chatham House Centre on Global Health Security facilitated a roundtable on civilian access to health care during conflict and a panel session entitled 'The Plot Sickens – The Health-Security Nexus'. This marked the first time health security had been featured in the main conference, and highlights the growing significance of health security to broader global stability and security. Chatham House produced, with support from the Gates Foundation, a short film including insights from UN Secretary-General Ban Ki-moon and Melinda Gates to introduce themes that were discussed as key security threats on the health-security nexus.

Initiated in 2015, the collaboration will continue with a Chatham House roundtable and a plenary session at the MSC’s Core Group Meeting in Addis Ababa in April, and further contributions to the 2017 MSC agenda.




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Oxford University Press to publish International Affairs

11 March 2016

Chatham House has signed an agreement with Oxford University Press (OUP) to publish International Affairs from 2017.

International Affairs, the institute’s peer-reviewed journal, has published high-quality, policy relevant articles for over 90 years and its global readership includes many of the world’s pre-eminent academic thinkers, policy-makers and practitioners. From January, when its current contract to publish with Wiley-Blackwell ends, OUP will assume responsibility to publish, distribute and market the journal to new and existing readers and audiences.

Vanessa Lacey, senior publisher for Oxford Journals, commented on the acquisition: 'We are thrilled to have been chosen by Chatham House to publish their prestigious journal International Affairs from 2017. International Affairs is a critically important, ‘must read’ journal of relevance to international relations academics and policy-makers alike. We look forward to partnering with Chatham House and International Affairs’ exceptional editorial team to reinforce its position as a global leader in its field.'

Robin Niblett, director of Chatham House, said: 'Chatham House is delighted to have teamed up with OUP, the world’s leading university press, to publish International Affairs. In terms of shared values, reputation and vision, OUP is an ideal partner for International Affairs and Chatham House. This is an exciting opportunity to develop further the journal’s digital outreach and its engagement with new audiences around the world.'

Andrew Dorman, commissioning editor of International Affairs also commented: 'The IA team is really pleased to be working in partnership with OUP to produce the journal. We share a common vision to publish cutting edge articles from across the discipline, which influence both the academic and practitioner communities in all parts of the world.'

OUP adds International Affairs, the foremost UK international relations journal and one of the top ten internationally, to a growing portfolio of respected international relations-related journals. 




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Prince Harry Opens the Stavros Niarchos Foundation Floor

16 June 2017

Prince Harry visited Chatham House on 15 June to open the Stavros Niarchos Foundation Floor.

His Royal Highness met with young fellows from the Queen Elizabeth II Academy for Leadership in International Affairs and discussed the important role that the next generation of leaders must play in bringing about positive change in their communities. 

The Academy was formally launched by Her Majesty The Queen at Chatham House in 2014.

Prince Harry also contributed to the first scenario exercise held in the institute’s new simulation centre, which explored how to respond to a humanitarian emergency that required landmine clearance, drawing on the prince’s work in the field of landmine eradication.

The opening of the Stavros Niarchos Foundation Floor marks a significant moment in the modern history of the institute and is a core component of the Chatham House Second Century Initiative, which aims to strengthen the institute’s capacity to innovate and meet the growing demand for its research in the lead-up to its centenary in 2020.

The extension includes a series of new facilities, including the Asfari Centre for Academy Fellows, the simulation centre, new meeting spaces and a media studio, which will ensure that Chatham House can continue to contribute to building a sustainably secure, prosperous and just world over the coming decades.

Mine Action in Angola: Landmine-Free by 2025

HM The Queen Launches Academy for Leadership




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Moving Energy Initiative Starts Clean Energy Projects for Refugees

26 June 2017

The Moving Energy Initiative starts four new clean energy projects for refugees.

Refugees in Burkina Faso, Kenya and Jordan will benefit from greater access to affordable, clean energy for domestic use and to power ‘microbusinesses’, following a grant scheme from the Moving Energy Initiative which launches today.

The Moving Energy Initiative is supporting projects ranging from a solar-powered ICT hub in Kenya’s Kakuma camp and vegetable growing zones watered by solar-powered pumps in Burkina Faso’s Goudoubo camp, to reliable energy generation for north Jordan’s Al Mafraq hospital where Syrian refuges and local residents access health care.

In total, four projects will be implemented over the next 12 months, with all involving training for refugees and local staff to use and maintain the clean energy technologies. They aim to deliver tangible reductions in CO2 emissions whilst increasing access to vital services, saving costs and providing livelihood opportunities for local communities and refugees. The projects are also expected to fuel entrepreneurship, opening up the potential for setting up businesses, small shops and restaurants which can expand beyond this initial grant.    

Project partners were chosen through an open and competitive process kicked off in February 2017 in Burkina Faso, Kenya and Jordan. Bidders were asked to demonstrate their ability to provide solutions that reduce fossil fuel consumption and increase access to energy in camps. The successful projects were chosen on the basis of the applicants’ ability to innovate in a humanitarian setting, as well as their track record and their approach to sustainability.

Find out more about why these projects are needed and the impact they aim to have by watching the video:

 

Check out the Moving Energy Initiative website for more information.

Keep updated on the progress of these projects as they develop by following us on Twitter @CH_EERD

 

Moving Energy Initiative: Sustainable Energy for Refugees and Displaced People

The Moving Energy Initiative Expert Workshop

Toolkits for the Moving Energy Initiative




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Chatham House awarded major centenary grant to establish Stavros Niarchos Foundation Wing

17 April 2019

Chatham House has been awarded a transformational £10m grant ahead of its upcoming 2020 centenary.

The gift will create the Stavros Niarchos Foundation (SNF) Wing, enabling a permanent expansion of the institute’s research and providing a home to its Queen Elizabeth II Academy for Leadership in International Affairs. The wing will also house the ‘Chatham House SNF CoLab’, an initiative to open Chatham House’s policy research to wider public audiences.

The funds from the Stavros Niarchos Foundation (SNF) will be used to integrate a three-storey wing with the institute’s renowned building at 10 St James’s Square. The SNF Wing will support research collaboration and provide a stimulating environment to explore ways to engage people in the institute’s research, using interactive multimedia and other digital tools. Inauguration of the Chatham House SNF CoLab and the SNF Wing is anticipated in fall of 2019.

The gift from SNF is one of the largest in the institute’s history and is a major milestone in the foundation’s long-standing support of Chatham House, which dates back to 2007 and includes grants for research, infrastructure and student outreach totalling over £4.5m in the past 5 years.

Chairman of Chatham House, Lord Jim O’Neill said, 'This exceptional gift from SNF is a vote of confidence in the independence, quality and impact of the institute’s work. It will guarantee that the institute can innovate for the future, especially by engaging younger generations into its research and ideas, which is essential.'

Director of Chatham House Dr Robin Niblett said the gift will encourage informed public debate at a time of unprecedented global uncertainty and deepening political polarisation.

'The SNF Wing and Chatham House SNF CoLab will ensure Chatham House can continue to serve as a trusted hub for dialogue and a source of credible information, analysis and ideas on international affairs. It is an enormous boost to our staff and their work as we begin our second century, and of special value in such turbulent times.'

SNF Co-President Andreas Dracopoulos said, 'Chatham House is one of our key partners, and this grant marks an important new stage in our collaboration. At a time of uncertainty in international affairs, supporting the world-class independent analysis that can help citizens around the world engage in informed decisions about their future is essential. We are proud to help Chatham House maintain its independent voice while deepening its engagement with the public.'

The Stavros Niarchos Foundation’s past support has enabled Chatham House to establish an ‘SNF Floor’ with a broadcast media studio, a purpose-built simulation centre and training facilities, which will now be incorporated into the larger SNF Wing. The floor was officially opened by His Royal Highness the Duke of Sussex in 2017, when he took part in a scenario exercise exploring how to respond to a humanitarian emergency that required landmine clearance, drawing on the Duke’s ongoing work in this field.

For more information please contact:

pressoffice@chathamhouse.org
Phone: +44 (0)207 957 5739

Editor's notes

Chatham House, the Royal Institute of International Affairs, is a world-leading policy institute based in London. Our mission is to help governments and societies build a sustainably secure, prosperous and just world.

We engage governments, the private sector, civil society and our members in open debate and private discussions about the most significant developments in international affairs.  Our research and policy ideas involve rigorous analysis of critical global, regional and country-specific challenges and opportunities.

The Stavros Niarchos Foundation (SNF) is one of the world’s leading private, international philanthropic organizations, making grants to non-profit organizations in the areas of arts and culture, education, health and sports, and social welfare. Since 1996, the Foundation has committed more than $2.8 billion, through more than 4,400 grants to non-profit organizations in 124 nations around the world.

The SNF funds organizations and projects worldwide that aim to achieve a broad, lasting and positive impact for society at large and exhibit strong leadership and sound management. The Foundation also supports projects that facilitate the formation of public-private partnerships as an effective means for serving public welfare.




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Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy

19 November 2019

The 2019 Chatham House Prize is awarded to Sir David Attenborough and Julian Hector, head of BBC Studios Natural History Unit, for the galvanizing impact of the Blue Planet II series on tackling ocean plastic pollution.

The Chatham House Prize is awarded to the person, persons or organization who is deemed to have made the most significant contribution to the improvement of international relations in the previous year. The presentation ceremony and panel discussion with the winners will be livestreamed on Wednesday.

The Blue Planet II series highlighted the damage caused by discarded plastics to the world’s oceans and marine wildlife. It is estimated that there are more than 150 million tonnes of plastic in the world’s oceans; resulting in the deaths of 1 million birds and 100,000 sea mammals each year. 

Dr Robin Niblett, director of Chatham House said: ‘Plastic pollution is one of the gravest challenges facing the world’s oceans, and undoubtedly an international issue. Sir David and the BBC Studios Natural History Unit played an instrumental role in helping to put this issue at the forefront of the public agenda. Blue Planet II spurred a passionate global response and generated clear behavioural and policy change.’

This year the G20 agreed on an international framework to address marine plastic litter, acknowledging the increasing urgency of the issue and the need for an international solution. This follows action from the UK government, including a plan to ban common plastic items and investment in global research.

See full award citation

Read more about Chatham House's research work in this area

Other nominees

Dr Niblett thanked Chatham House members for voting and acknowledged the outstanding achievements of the 2019 nominees:

Abiy Ahmed, prime minister of Ethiopia, nominated for his efforts to transform civic leadership and promote plural politics, free speech and peace in Ethiopia 

Katrín Jakobsdóttir, prime minister of Iceland, nominated for her commitment to gender equality and women’s financial inclusion in Iceland 

Event

The Prize was presented to Sir David and Julian Hector by Her Majesty The Queen at Chatham House on Wednesday 20 November.

Watch video from the event

For more information please contact

Chatham House Press Office
pressoffice@chathamhouse.org
+44 (0)207 957 5739

BBC Studios Natural History Unit Communications Manager
Lynn.li@bbc.co.uk
+44 (0) 7513 137893

About the Chatham House Prize

The Chatham House Prize is voted for by Chatham House members, following nominations from the institute’s staff. The award is presented on behalf of the institute's patron, Her Majesty the Queen, representing the non-partisan and authoritative character of the Prize.

The Chatham House Prize was launched in 2005. Previous recipients of the Prize include the Committee to Protect Journalists, Colombian president Juan Manuel Santos, president of Ghana John Kufuor, Médecins Sans Frontières and Melinda Gates, co-founder of the Bill and Melinda Gates Foundation.

Chatham House is a world-leading policy institute based in London. Our mission is to help governments and societies build a sustainably secure, prosperous and just world. We engage governments, the private sector, civil society and our members in open debate and private discussions about the most significant developments in international affairs.  Our research and policy ideas involve rigorous analysis of critical global, regional and country-specific challenges and opportunities.

About BBC Studios Natural History Unit 

BBC Studios Natural History Unit produces the world’s most iconic natural history programmes, such as Blue Planet II and Planet Earth II, which have been watched by more than a billion people globally. Ranging from technically challenging live shows and super-landmarks to long-running series and children’s content, The Natural History Unit programmes include Dynasties, Blue Planet Live, Springwatch, Animal Babies: First Year On Earth, Andy’s Dinosaur Adventures as well as the currently on air Seven Worlds, One Planet presented by Sir David Attenborough and third-party commissions for Discovery, Apple, Quibi, National Geographic and BBC America. 

The Natural History Unit is part of BBC Studios, a subsidiary of the BBC, which develops, produces and distributes bold, British content, making over 2,500 hours of content each year, operating in 22 markets globally and generating revenue of around £1.4bn. In the year to March 2019, it returned £243m to the BBC Group, complementing the BBC’s licence fee and enhancing programmes for UK audiences.




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Screening Room: For Sama

Members Event Screening Room

1 October 2019 - 6:00pm to 8:15pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Hamza Al Kateab, Director, AlQudes Hospital, Aleppo (2012-16); Operation Manager, Huozhi
Rita Dayoub, Academy Associate, Centre on Global Health Security, Chatham House; Founder, Health Workers at the Frontline Initiative
Dr Husam Taha El-mugamar, Vice President, Sudan Doctors’ Union UK
Chair: Elham Saudi, Director, Lawyers for Justice in Libya

For Sama tells the story of a young woman living in Aleppo during a five year period of armed conflict. From 2011 to 2016, Waad al-Kateab documents her personal experience of the war in Syria as she joins the uprising against the Assad regime, falls in love and gives birth to her daughter while living in AlQudes Hospital, run by her husband Hamza and under attack by Syrian and Russian forces.

The screening will be followed by a panel discussion exploring the impact of attacks on healthcare institutions in conflict zones. To what extent are attacks on healthcare services used in contemporary warfare? How do these attacks affect health workers in regions facing armed conflict or political unrest? And what is the role of the international community in ensuring the protection of healthcare delivery in conflict zones?

Running time: 95 mins

This event is open to Chatham House Members only. Not a member? Find out more.

For further information on the different types of Chatham House events, visit Our Events Explained.

Members Events Team




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The Political Economy of Universal Health Coverage

Corporate Members Event Nominees Breakfast Briefing Partners and Major Corporates

22 January 2020 - 8:00am to 9:15am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Robert Yates, Head, Centre on Global Health Security, Chatham House
Chair: Professor David R Harper, Senior Consulting Fellow, Centre on Global Health Security, Chatham House; Managing Director, Harper Public Health Consulting Limited
 

At the United Nations General Assembly in September 2019, all governments re-committed their countries to achieving universal health coverage (UHC) whereby ‘all people obtain the health services they need without suffering financial hardship when paying for them’. To achieve UHC, governments will need to oversee health systems that are predominantly publicly financed although countries may use both private and public health providers of health services.

Robert Yates will provide a review of recent transitions towards Universal Health Coverage, highlighting the importance of genuine political commitment by heads of state, and the potential benefits to corporate stakeholders in helping reach this sustainable development goal. What are the political, economic and health benefits of UHC? Why can only public financing mechanisms, rather than a free market in health services, deliver an equitable health system? And what is the role of the private sector within the political economy of UHC?

This event is only open to Major Corporate Member and Partner organizations of Chatham House. If you would like to register your interest, please RSVP to Linda Bedford. We will contact you to confirm your attendance.

To enable as open a debate as possible, this event will be held under the Chatham House Rule.

Event attributes

Chatham House Rule

Members Events Team




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New Coronavirus Outbreak: Concern Is Warranted, Panic Is Not

23 January 2020

Professor David Heymann CBE

Distinguished Fellow, Global Health Programme

Lara Hollmann

Research Assistant, Global Health Programme
Whenever there is a new infection in humans, such as the novel coronavirus, it is appropriate to be concerned because we do not know enough about its potential.

Explainer: Coronavirus - What You Need to Know

World-renowned global health expert Professor David Heymann CBE explains the key facts and work being done on the Coronavirus outbreak.

When it comes to emerging infectious diseases – those newly recognized in humans or in new locations – it is not only what we know that matters but also what we do not know.

An outbreak of a new coronavirus first reported in Wuhan, China, which has so far led to more than 500 confirmed cases and multiple deaths across five countries (and two continents) has prompted the question from several corners of the world: Should we be worried?

Although expert teams coordinated by the World Health Organization (WHO) are working on key questions to get answers as soon as possible, the level of uncertainty is still high.

We do not yet know exactly how deadly the disease is, how best to treat those who get sick, precisely how it is spreading, nor how stable the virus is. It is thought that the virus spread from an animal source, but the exact source is yet to be confirmed and the disease is now in human populations and appears to be spreading from human to human.

It is such uncertainty, inherent in emerging infectious disease outbreaks, that warrants concern. Until they are resolved, it is appropriate for the world to be concerned. It is useful to remember that most established scourges of humanity such as HIV, influenza and tuberculosis likely started as emerging infectious diseases that jumped the species barrier from animals to humans.

Shortly after the Chinese authorities reported the first cases of ‘mystery pneumonia’ in Wuhan, China, to WHO, the virus causing the disease was isolated and identified as being part of the coronavirus family. It belongs to the same virus family as SARS, a highly contagious and life-threatening coronavirus that caused a nine-month epidemic in 2003 that affected 26 countries and resulted in more than 8,000 infections and nearly 800 deaths.

A second novel coronavirus that emerged in 2012 and persists today – MERS, or Middle East Respiratory Syndrome – is less contagious (spread by close contact rather than coughing and sneezing).

The differences between the SARS coronavirus and the MERS coronavirus highlight that, despite belonging to the same virus family, pathogens do not necessarily behave in the same way. It is as yet unknown whether the new virus is, or will turn out to be, more like SARS or MERS, or neither. 

Chinese authorities have confirmed that there is human-to-human transmission. However, it is not yet established whether it is sustained, which would make the outbreak more difficult to control. As of 23 January, the number of cases range from 500 confirmed cases up to an estimated 1,700 cases, according to a disease outbreak model by Imperial College London.

Likewise, we do not know to what extent the virus is able to mutate and if so, how rapidly. Generally, coronaviruses are known to be able to mutate, with the risk that a less contagious form of the virus becomes highly contagious. This could have an impact not only on the transmission pattern and rate but also the death rate. The virus could change in either direction, to become either more or less of a threat.

It is important to take a precautionary approach while uncertainty persists. It is also important not to overreact and for measures to be scientifically sound. Concern over this outbreak is due, but panic is not.

Three virtual networks of experts supporting the response – one of virologists, one of epidemiologists and one of clinicians – are working on the key pieces of the jigsaw puzzle: watching the virus, watching the transmission patterns, and watching the people who have been infected. It is crucial to maintain the ongoing investigation of the disease, stay focused on the science and to keep sharing the necessary information.




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Nina van der Mark

Research Analyst, Global Health Programme

Biography

Nina works on universal health coverage (UHC) and health system reforms. Her research is primarily focused on the political economy of UHC and accelerating health system reforms in low-and-middle income countries.

Previously, Nina worked as an international development professional, focused on health financing and advocacy in the fields of sexual and reproductive health and rights, youth participation and maternal and child health. Nina has experience working in Ethiopia and Nigeria. She has also worked for the private sector as a healthcare technology research consultant for Southeast Asia.

She has a broad-based interest in global health, including the influence of demographic changes on population health outcomes, innovative health financing mechanisms and improving research uptake into health policy.

She has a multidisciplinary background and holds a Msc in Population and Development at The London School of Economics (LSE) and a BA in Liberal Arts and Sciences, focused on international relations, international law and China studies at University College Utrecht. 




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How Concerning Is the New Coronavirus Outbreak?

Members Event

26 February 2020 - 1:00pm to 2:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Professor David Heymann CBE, Distinguished Fellow, Global Health Programme, Chatham House; Executive Director, Communicable Diseases Cluster, World Health Organization (1998-03)
Chair: Emma Ross, Senior Consulting Fellow, Global Health Programme, Chatham House

Professor Heymann, who previously led the World Health Organization’s response to SARS and has been advising the organization on its response to the coronavirus, outlines the key facts relating to this outbreak and reflect on the challenges it poses. 

An outbreak of a new coronavirus first reported in Wuhan, China has so far spread to dozens of countries, led to tens of thousands of confirmed cases and almost 2,000 deaths. The World Health Organization has declared the situation a global health emergency thereby prompting questions from around the world about how worried the public should be and how can governments, media, civil society and the global health community best tackle new infectious disease outbreaks?

What do we know – and what do we not know – about this coronavirus at the moment? What lessons learned from previous outbreaks have been applied – and not applied – to this outbreak? How can governments and the media balance public awareness and the risk of panic? And what measures can be taken to reduce the risk of stigma and discrimination of populations during this and other outbreaks?

Members Events Team




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Webinar: European Union – The Economic and Political Implications of COVID-19

Corporate Members Event Webinar

26 March 2020 - 5:00pm to 5:45pm

Online

Event participants

Colin Ellis, Chief Credit Officer, Head of UK, Moody’s Investors Service
Susi Dennison, Director, Europe Power Programme, European Council of Foreign Relations
Shahin Vallée, Senior Fellow, German Council of Foreign Relations (DGAP)
Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House

Chair: Hans Kundnani, Senior Research Fellow, Europe Programme, Chatham House


 

In the past few weeks, European Union member states have implemented measures such as social distancing, school and border closures and the cancellation of major cultural and sporting events in an effort to curb the spread of COVID-19. Such measures are expected to have significant economic and political consequences, threatening near or total collapse of certain sectors. Moreover, the management of the health and economic crises within the EU architecture has exposed tensions and impasses in the extent to which the EU is willing to collaborate to mitigate pressures on fellow member states.

The panellists will examine the European Union's response to a series of cascading crises and the likely impact of the pandemic on individual member states. Can the EU prevent an economic hit from developing into a financial crisis? Are the steps taken by the European Central Bank to protect the euro enough? And are member states expected to manage the crisis as best they can or will there be a united effort to mitigate some of the damage caused?  

This event is part of a fortnightly series of 'Business in Focus' webinars reflecting on the impact of COVID-19 on areas of particular professional interest for our corporate members.

Not a corporate member? Find out more.

 




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Coronavirus Risks Worsening a Food Crisis in the Sahel and West Africa

1 May 2020

Dr Leena Koni Hoffmann

Associate Fellow, Africa Programme

Paul Melly

Consulting Fellow, Africa Programme
In responding to the spread of the coronavirus, the governments of the Sahel and West Africa will need to draw on their collective experience of strategic coordination in emergency planning, and work together to prioritize the flow of food across borders.

2020-05-01-Africa-Market-Virus

An informal market in the Anyama district of Abidjan, Côte d’Ivoire, is sanitized against the coronavirus. Photo by SIA KAMBOU/AFP via Getty Images.

The COVID-19 pandemic has struck the Sahel and West Africa at a time when the region is already under severe pressure from violent insecurity and the effects of climate change on its land, food and water resources.

By the end of April, there had been 9,513 confirmed coronavirus cases across the 17 countries of the region, and some 231 deaths, with the highest overall numbers recorded in Nigeria, Ghana, Guinea, Côte d’Ivoire, Senegal, Niger and Burkina Faso. Low testing rates mean than these numbers give only a partial picture.

The Food Crisis Prevention Network (RPCA) forecast in early April that almost 17 million people in the Sahel and West Africa (7.1 million in Nigeria alone) will need food and nutritional assistance during the coming lean season in June–August, more than double the number in an average year. The combined impact of violent insecurity and COVID-19 could put more than 50 million other people across the region at risk of food and nutrition crisis.

Rippling across the region

The effects of the collapse in global commodity prices, currency depreciations, rising costs of consumer goods and disruptions to supply chains are rippling across the region. And for major oil-exporting countries such as Nigeria, Ghana, Chad and Cameroon, the wipe-out of foreign currency earnings will hammer government revenues just as the cost of food and other critical imports goes up. It is likely that the number of people who suffer the direct health impact of the coronavirus will be far outstripped by the number for whom there will be harsh social and economic costs.

In recent years, valuable protocols and capacities have been put in place by governments in West and Central Africa in response to Ebola and other infectious disease outbreaks.

But inadequate healthcare funding and infrastructure across this region compound the challenge of responding to the spread of the COVID-19 infection – which is testing the resources of even the world’s best-funded public health systems.

Over many years, however, the region has steadily built up structures to tackle humanitarian and development challenges, particularly as regards food security. It has an established system for assessing the risk of food crisis annually and coordinating emergency support to vulnerable communities. Each country monitors climate and weather patterns, transhumance, market systems and agricultural statistics, and terrorist disruption of agricultural productivity, from local community to national and regional level.

The system is coordinated and quality-controlled, using common technical data standards, by the Permanent Interstate Committee for Drought Control in the Sahel (CILSS), a regional intergovernmental body established in 1973 in response to a devastating drought. Collective risk assessments allow emergency support to be mobilized through the RPCA.

For almost three months already, countries in Sahelian West Africa have been working with the World Health Organization to prepare national COVID-19 response strategies and strengthen health controls at their borders. Almost all governments have also opted for domestic curfews, and variations of lockdown and market restrictions.

Senegal has been a leader in rapidly developing Africa’s diagnostic capacity, and plans are under way to speed up production of test kits. Niger was swift to develop a national response strategy, to which donors have pledged €194.5 million. While the IMF has agreed emergency financial assistance to help countries address the urgent balance-of-payments, health and social programme needs linked to the COVID-19 pandemic, signing off $3.4 billion for Nigeria, $442 million for Senegal and $130 million for Mauritania.

Steps are also now being taken towards the formulation of a more joined-up regional approach. Notably, Nigeria’s President Muhammadu Buhari has been chosen by an extraordinary session of the Economic Community of West African States to coordinate the regional response to COVID-19. As Africa’s biggest economy and home to its largest population, Nigeria is a critical hub for transnational flows of goods and people. Its controversial August 2019 land border closure, in a bid to address smuggling, has already painfully disrupted regional agri-food trade and value chains. The active engagement of the Buhari administration will thus be crucial to the success of a multifaceted regional response.

One of the first tough questions the region’s governments must collectively address is how long to maintain the border shutdowns that were imposed as an initial measure to curb the spread of the virus. Closed borders are detrimental to food security, and disruptive to supply chains and the livelihoods of micro, small and medium-sized entrepreneurs that rely on cross-border trade. The impact of prolonged closures will be all the more profound in a region where welfare systems are largely non-existent or, at best, highly precarious.

Nigeria, in particular, with more than 95 million people already living in extreme poverty, might do well to explore measures to avoid putting food further beyond the reach of people who are seeing their purchasing power evaporate.

In taking further actions to control the spread of the coronavirus, the region’s governments will need to show faith in the system that they have painstakingly developed to monitor and respond to the annual risk of food crisis across the Sahel. This system, and the critical data it offers, will be vital to informing interventions to strengthen the four components of food security – availability, access, stability and utilization – in the context of COVID-19, and for charting a post-pandemic path of recovery.

Above all, careful steps will need to be put in place to ensure that preventing the spread of the coronavirus does not come at the cost of even greater food insecurity for the people of the Sahel and West Africa. The region’s governments must prioritize the flow of food across borders and renew their commitment to strategic coordination and alignment.




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The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus [Gene Regulation]

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.




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The mRNA levels of heat shock factor 1 are regulated by thermogenic signals via the cAMP-dependent transcription factor ATF3 [Metabolism]

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues.




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Inflammatory and mitogenic signals drive interleukin 23 subunit alpha (IL23A) secretion independent of IL12B in intestinal epithelial cells [Signal Transduction]

The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11–7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion.







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Analysis of the Subunit Composition of Complex I from Bovine Heart Mitochondria

Joe Carroll
Feb 1, 2003; 2:117-126
Research




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Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources




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Large Scale Screening for Novel Rab Effectors Reveals Unexpected Broad Rab Binding Specificity

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research




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A Tandem Affinity Tag for Two-step Purification under Fully Denaturing Conditions: Application in Ubiquitin Profiling and Protein Complex Identification Combined with in vivoCross-Linking

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research




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Trypsin Cleaves Exclusively C-terminal to Arginine and Lysine Residues

Jesper V. Olsen
Jun 1, 2004; 3:608-614
Technology




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Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins

Leigh Anderson
Apr 1, 2006; 5:573-588
Research




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Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology




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Learning the ABCs of ATP release [Signal Transduction]

ATP plays important roles outside the cell, but the mechanism by which it is arrives in the extracellular environment is not clear. Dunn et al. now show that decreases in cellular cholesterol levels mediated by the ABCG1 transporter increase ATP release by volume-regulated anion channels under hypotonic conditions. Importantly, these results may imply that cells that handle cholesterol differently might experience differential extracellular ATP release during hypotonicity.




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ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity [Signal Transduction]

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.