The University of East Anglia is an English public research university located in the city of Norwich. Established in 1963, the university comprises 4 faculties and 28 schools of study. Situated to the south-west of the city of Norwich, the university campus is approximately 320 acres in size.In 2012 the University was named the 10th best university in the world under 50 years old, and 3rd within the United Kingdom. In national league tables the university has most recently been ranked 14th in the UK by The Times and Sunday Times, 14th by The Guardian and 15th by The Complete University Guide. The university also ranked 1st for student satisfaction by the Times Higher Education magazine in 2013.Notable alumni include Nobel Laureate and President of the Royal Society Sir Paul Nurse, King of Tonga Tupou VI, and the Booker Prize-winning authors Ian McEwan, Kazuo Ishiguro and Anne Enright. Wikipedia.
University of East Anglia | Date: 2013-05-31
The present invention relates to methods of synthesising aziridines including isotopically labelled aziridines, said methods comprising contacting an imine or one or more precursors thereof with a diazo compound in the presence of a phosphoramide or a phosphoramide-derived catalyst. The present invention also relates to aziridines, modified aziridines and aziridine-derived compounds preparable by the aforementioned methods, and to phosphoramide or phosphoramide-derived catalysts suitable for use in such methods.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: LCE-21-2015 | Award Amount: 4.00M | Year: 2016
SET-Nav will support strategic decision making in Europes energy sector, enhancing innovation towards a clean, secure and efficient energy system. Our research will enable the EC, national governments and regulators to facilitate the development of optimal technology portfolios by market actors. We will comprehensively address critical uncertainties and derive appropriate policy and market responses. Our findings will support the further development of the SET-Plan and its implementation by continuous stakeholder involvement. These contributions of the SET-Nav project rest on three pillars: The wide range of objectives and analytical challenges set out by the call for proposals can only be met by developing a broad and technically-advanced modelling portfolio. Advancing this portfolio and enabling knowledge exchange via a modelling forum is our first pillar. The EUs energy, innovation and climate challenges define the direction of a future EU energy system, but the specific technology pathways are policy sensitive and need careful comparative evaluation. This is our second pillar. Using our strengthened modelling capabilities in an integrated modelling hierarchy, we will analyse multiple dimensions of impact of future pathways: sustainability, reliability and supply security, global competitiveness and efficiency. This analysis will combine bottom-up case studies linked to the full range of SET-Plan themes with holistic transformation pathways. Stakeholder dialogue and dissemination is the third pillar of SET-Nav. We have prepared for a lively stakeholder dialogue through a series of events on critical SET-Plan themes. The active involvement of stakeholders in a two-way feedback process will provide a reality check on our modelling assumptions and approaches, and ensure high policy relevance. Our aim is to ensure policy and market actors alike can navigate effectively through the diverse options available on energy innovation and system transformation.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC5-06-2016-2017 | Award Amount: 5.88M | Year: 2016
EUCalc replies to topic a) Managing technology transition. The EUCalc project will deliver a much needed comprehensive framework for research, business, and decision making which enables an appraisal of synergies and trade-offs of feasible decarbonisation pathways on the national scale of Europe and its member countries \ Switzerland. The novel and pragmatic modelling approach is rooted between pure complex energy system and emissions models and integrated impact assessment tools, introduces an intermediate level of complexity and a multi-sector approach and is developed in a co-design process with scientific and societal actors. EUCalc explores decisions made in different sectors, like power generation, transport, industry, agriculture, energy usage and lifestyles in terms of climatological, societal, and economic consequences. For politicians at European and member state level, stakeholders and innovators EUCalc will therefore provide a Transition Pathways Explorer, which can be used as a much more concrete planning tool for the needed technological and societal challenges, associated inertia and lock-in effects. EUCalc will enable to address EU sustainability challenges in a pragmatic way without compromising on scientific rigour. It is meant to become a widely used democratic tool for policy and decision making. It will close - based on sound model components - a gap between actual climate-energy-system models and an increasing demands of decision makers for information at short notice. This will be supported by involving an extended number of decision-makers from policy and business as well as other stakeholders through expert consultations and the co-design of a Transition Pathways Explorer, a My Europe 2050 education tool and a Massive Open Online Course.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC5-06-2016-2017 | Award Amount: 2.99M | Year: 2016
The COP21 outcome represents an important new strategic context for EU climate policy. Analysing the implications of this new context requires an interdisciplinary approach, combining analysis of the evolution of the international climate regime as well as of NDCs and their socio-economic implications. Such analysis is also urgent, given the timelines imposed by the Paris Agreement for a facilitative dialogue in 2018 with a view to creating the conditions for the revision of NDC in 2020. In order to address the context described above, this project has four objectives : 1) Assess the adequacy of the NDCs submitted at COP21 in light of the global temperature target of limiting warming to 2C/1.5C. Through the analysis of GHG scenarios and energy system scenarios , the project will pay particular attention to the concrete system changes induced by NDCs, and compare them with the changes required to meet the global temperature limit. The project will also analyse scenarios limiting warming to 1.5C, and the impact of NDCs on other sectors, in particular land-use. 2) Assess the implications of NDCs and deeper mitigation pathways on other European socio-economic objectives. By integrating GHG and energy system scenarios into a range of different macro-economic, global energy system models and other quantified methodologies, the project will investigate implications for European socio-economic objectives related to innovation and technology deployment; trade and competiveness; investment, financial flows and economic growth (green growth); and global energy markets and energy security. 3. Assess the adequacy of the outcomes of COP21, and the implications and opportunities emerging from ongoing UNFCCC negotiations. The project will undertake a social sciences-based (in particular international law and international relations) assessment of the outcome of COP21. 4) Policy recommendations for EU climate policy and climate diplomacy.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.46M | Year: 2016
Deictic communication is fundamental to understanding communication in both typical and atypical populations, and forms the key connection between language and objects/locations in the world. It is therefore critical to understanding human-human interaction, and human-system interaction in a range of technology applications from mobile phones to cognitive robotics and to the enhancement of clinical and educational interventions with typical and atypical populations. This ETN will train the next generation of scientists in the full range of multidisciplinary and cross-sectorial methods necessary to make significant progress in understanding deictic communication, with direct synergies between basic research and application. Training is structured around two interdisciplinary research themes Understanding Deictic Communication and Deictic Communication in Application both involving extensive and systematic co-supervision and collaboration across sites with key interplay between academic and nonacademic beneficiaries and partners. In turn we expect that a range of applications will be enhanced with increased usability, with associated societal and economic benefit. The training of the cohort of ESR fellows is based on innovative PhD training approaches, providing not only training in interdisciplinary methods, but also employing peer-assisted methods and the latest in educational innovation. This will produce a cohort of highly skilled researchers who will be highly employable given the potential contribution they will make to future research and innovation in the public and private sectors.
Munoz M.P.,University of East Anglia
Chemical Society Reviews | Year: 2014
Transition-metal catalysed nucleophile addition to allenes is a very powerful tool for the synthesis of functionalised molecules containing heteroatoms, heterocycles in the intramolecular version, or allyl derivatives in the intermolecular version. The reaction has been explored with a wide variety of metals, silver being one of the most effective. Although platinum has somehow been less explored, different reactivities have been observed with this metal, showing the great potential and versatility of this methodology. This review will highlight the reactions with these two metals, silver and platinum, when oxygen or nitrogen nucleophiles are employed. Although most of the examples describe the intramolecular version, some intermolecular reactions with platinum have been described, and will also be covered. This journal is © the Partner Organisations 2014.
Agency: GTR | Branch: BBSRC | Program: | Phase: Research Grant | Award Amount: 403.43K | Year: 2017
Nitric oxide (NO) is a toxic molecule that is generated by soil bacteria and in our bodies as a defence against pathogenic organisms trying to establish infection. One of the major ways by which NO exerts its toxic effects is through reaction with a widespread group of proteins that bind a type of cofactor containing both iron and sulfur arranged as a cluster. Members of this group play crucial roles in a very wide range of processes, including respiration and protein synthesis. To avoid NO toxicity, pathogenic (as well as harmless) organisms have evolved protective systems that detoxify NO by removing it through chemical reaction. The fact that iron-sulfur clusters are particularly sensitive to NO (and their modification is a major route by which NO exerts its toxic effects) has been exploited in nature, through the evolution of a number of regulatory proteins that themselves contain an iron-sulfur cluster and which function as biological switches, turning on the cellular detoxification response in the presence of NO. Despite the importance and widespread nature of the reaction of iron-sulfur clusters with NO, we still know relatively little about this process. Some important progress has been made in recent years, but the difficulties associated with working with iron-sulfur proteins, which are fragile and must be handled in O2-free environments, and with detecting and unambiguously identifying intermediates and products of the cluster reaction with NO have, up to now, been major obstacles. The project described in this proposal will lead to a major advance in our understanding of how NO-responsive iron-sulfur cluster-containing regulators function. The major subject of our proposed study is an iron-sulfur cluster regulator that is a member of a large and not well understood family of regulators found in a wide range of pathogenic and non-pathogenic bacteria, in which it functions as a primary NO sensor by controlling the cellular response to NO toxicity. We will also study a second regulatory protein that belongs to a family found only in a small number of bacteria, but which includes the pathogen that causes tuberculosis, one of the worlds major killers, and the bacterium that is the source of many of the antibiotics currently in use in the clinic. Members of this family play key roles in cell developmental processes associated with stress response, including sporulation and dormancy, which is important for the ability of the tuberculosis pathogen to survive in the inhospitable environment of a human host for years, in a state that is highly resistant to antibiotics. The project will build on three important recent breakthroughs. Firstly, we have established novel mass spectrometry methodologies that enable us to detect iron-sulfur cluster regulators with their clusters intact. This now provides the opportunity to follow by mass spectrometry the reaction of the cluster with NO by detecting and identifying intermediates and products formed. Secondly, we have developed novel ways of studying the same proteins using vibrational spectroscopy, providing characteristic signatures according to the iron-NO complexes formed. Finally, working with a group in France, we have determined the high resolution structure of one of the regulators with its iron-sulfur cluster bound. This is a first for this family of iron-sulfur cluster regulators and provides the ideal basis on which to understand how the cluster promotes DNA binding and how it reacts with NO. We will exploit these recent advances to explore using a range of approaches the biochemistry of the reaction of NO with these proteins, revealing unprecedented mechanistic insight into how NO-sensing regulatory proteins function, and providing clues about how NO sensing, and therefore survival, of pathogens could be disrupted/prevented.
Agency: GTR | Branch: BBSRC | Program: | Phase: Research Grant | Award Amount: 386.26K | Year: 2017
The extraordinary properties of living systems emerge as a result of dynamic interactions between their biomolecular components (proteins, nucleic acid, carbohydrates or glycans, ...). Despite the complexity of a system of millions of molecular interactions, the whole network of interactions is highly regulated for healthy organisms, and alterations in the regulation processes underlie all diseases. In this network, different molecules interact with different strengths (affinities), where strong interacting partners produce stable biomolecular complexes and weak binding molecules produce transient assemblies. A well orchestrated system of protein-ligand interactions of very different affinities is indeed responsible for most of the regulation processes in living organisms. Strong complexes are formed when sustained biological signals are needed, whereas weak interactions are recalled when quick cellular responses are required after temporary stimuli (signal transduction, reversible cell-cell contacts, transient interactions in host/pathogen recognition, etc.). For a complete understanding of life processes, it is necessary to investigate both strong and weak protein-ligand interactions, which encourages the development of novel approaches to characterize the 3D molecular structures of weak protein complexes. Strong protein-ligand interactions have been extensively investigated and many biologically relevant 3D complexes have been determined, as their intrinsic stability makes them amenable to a number of analytical techniques. However, for weak protein interactions many conventional approaches fail or become unreliable. For example, X-ray crystallography, a very powerful structural technique, show limitations for weak interactions as: (i) obtaining crystals of the complexes including the ligand is difficult, and (ii) the typically poorly defined electronic density that describe the ligand in the binding pocket. NMR spectroscopy, one of the most powerful techniques to study intermolecular interactions, has demonstrated its extraordinary capability for the detection of weak protein-ligand interactions in solution, through the use of ligand-based experiments, like Saturation Transfer Difference (STD) NMR spectroscopy. However, the translation from these experiments to 3D structures is currently not straightforward. We have published some improvements in the set up of STD NMR experiments to determine protein-ligand affinities and study multiple binding modes of ligands in a protein binding pocket. The present proposal stems from recent results in our research group that allow us to propose that STD NMR spectroscopy can provide more structural information for weak interactions than the map of ligand contacts, or group epitope mapping (GEM). Here, we propose to obtain the orientation of the ligand in the binding pocket, a much needed piece of information. We plan to generate new experimental restraints to drive the structural calculations of the complexes, to get accurate 3D structures. Until now, these experimental restraints have remained unexplored. Among the most biologically relevant weak interactions, those of proteins with glycans are essential steps in many cell-cell communication processes, and key in the infectivity of microbial pathogens. In particular, influenza virus exploits this for initial cell recognition, attachment, and release of new virions. In a different strategy, HIV covers its surface with host glycans to evade the immunological response. Interestingly, new broad neutralizing antibodies (bNAb) are being discovered which are able to stop infection and are elicited against those carbohydrates in that glycan shield. In the context of our collaborations with Prof. Rob Field (Norwich) and Dr. Katie Doores (London), we will apply the novel STD NMR approaches to investigate the molecular recognition processes in human and avian influenza virus, and in immunologically active bNAbs against HIV.
Agency: GTR | Branch: BBSRC | Program: | Phase: Research Grant | Award Amount: 392.67K | Year: 2017
Almost all the antibiotics used in human medicine were discovered >50 years ago and most disease-causing bacteria are now resistant to one or more of these drugs. This means humans are facing a return to the pre-antibiotic era, an alarming situation that has been described as antibiotic Armageddon. The government commissioned ONeill review on AntiMicrobial Resistance (AMR) estimates that if we do not kick-start antibiotic discovery efforts now then by 2050 drug resistant infections will kill more people than cancer, an estimated 10 million a year. Most of the antibiotics we currently use are natural products derived from the secondary metabolites of soil bacteria and the most important group are called Streptomyces, which make 50% of all known antibiotics. Streptomyces are incredibly important to humans and although scientists have already discovered lots of antibiotics from these bacteria we now know that they only found the really easy to find compounds, the low hanging fruit. Genome sequencing over the last 15 years has revealed that Streptomyces bacteria only make about 25% of their secondary metabolites under laboratory conditions which means that from 1940-60, the so-called golden age of antibiotic discovery, scientists were barely sampling their capability. The rest are called silent secondary metabolites because they do not make them in the lab. The good news is this means we have a big advantage over scientists working in the 20th century - if we can find ways to switch on production of all the silent secondary metabolites in the >600 known species we will find lots of new antibiotics that can enter the clinical trials pipeline. This is the earliest stage in antibiotic discovery and it is vital that we increase our efforts now because it takes 10-15 years to get drugs through clinical trials and approved for use in humans. Probably <1% of antibiotics will be suitable for treating disease so the more natural products we can discover from Streptomyces in the next few decades the better. One way to activate the production of silent secondary metabolites is to understand the natural signals and signalling pathways that control their production in the soil and this is the focus of our research. If we can manipulate those signalling pathways we can force the bacteria to make all of their antibiotics in the laboratory. Ideally we want to identify signalling pathways which effect antibiotic production in all 600+ known Streptomyces species and this is the subject of our proposal. We have identified a signalling pathway consisting of two proteins called MtrA and MtrB and found this is the only conserved and essential pathway in the genus Streptomyces. This means this MtrAB two-component system is found in every single sequenced Streptomyces strain! MtrA is a DNA binding protein and its activity is controlled by the signal sensing protein MtrB. If we disrupt the pathway by deleting the mtrA gene it is lethal. If we delete the mtrB gene it removes the need for an environmental signal to activate the pathway and results in over-production of active MtrA protein which switches on production of antibiotics that are usually silent in the wild-type strains. However, simply over-producing MtrA does not work, we HAVE to remove MtrB as well. In this project we will analyse MtrAB in two model species called S. coelicolor and S. venezuelae. We will determine how MtrB controls MtrA activity, why MtrA is active in the absence of MtrB and why and how MtrA activates the production of silent secondary metabolites. We will also try to make gain of function MtrA proteins that are always active and see if we can use them to switch on antibiotic production in our model strains and in two new talented Streptomyces species that we have isolated and genome sequenced. We call them talented because they appear to encode many novel secondary metabolites and MtrA may allow us to discover new antibiotics from these strains.
Agency: GTR | Branch: AHRC | Program: | Phase: Research Grant | Award Amount: 779.25K | Year: 2017
Literary writers have often seen their poems, plays, essays and novels censored on grounds of offence, blasphemy, libel, political sedition or obscenity and they have also often been eloquent defenders of the right to free expression. This project investigates the intimate relationship between literature and free speech, but focuses on its particular features in twentieth and twenty-first century history. Article 19 of the Universal Declaration of Human Rights (UDHR) in 1948, insisted on the right to freedom and expression...regardless of frontiers. But writers had, since the 1920s, been claiming that, literature knows no frontiers, as the organisation International PEN put it in 1927 and that the dissemination, readership and future significance of literary works could not be owned by nation states. The relationship between literature, censorship and free expression has been of considerable and longstanding interest to lawyers and legal scholars, (Thomas , Dhavan ), literary critics (Pease , McDonald ) and intellectual historians, (Collini , Darnton . Recent histories of human rights, meanwhile, have analysed the cultural battles over what was universal about rights in the lead up to the UDHR, and its subsequent history (Moyn , Mazower [2009, 2012]). The specific relationship between literature and rights, meanwhile, has also been of considerable interest (Hunt , Slaughter , Anker ). This project engages with this wider body of scholarship, but shifts the terms of the debate. It argues that in order to understand the impact of twentieth and twenty-first century writers on understandings of free expression it is necessary to analyse different sites of cultural exchange, looking beyond governments, law and declarations,. This project argues that the non-governmental writers organisation has also played a crucial role. It focuses on one writers organisation, International PEN, but also looks at associated organisations in its three key areas of focus: the UK, South Africa and India. International PEN was founded in London in 1921 but quickly expanded, with centres springing up across Europe and the US in 1922 and 1923, and in China (1924), Canada (1926), South Africa (1927), Argentina (1930), India (1933), Japan and Brazil (1934), amongst many others. Its members have included some of the most prominent writers of the long twentieth century, including Rabindranath Tagore, Toni Morrison, Margaret Atwood, and Salman Rushdie. Many member writers have had their works censored; and many of them have written influential essays, poems, plays or novels reflecting on the boundaries of free expression. Not only have these writers, and these writers organisations, engaged intellectually with attacks on free speech; they have also influenced government policies, international charters and legal interpretations through campaigning, educational and translation initiatives. When PEN began in the 1920s its internationalism entailed an expansionist and supposedly apolitical spirit of international friendliness through encounters with writers from other cultures. The organisations understanding of internationalism, however, soon changed, firstly in its attempt to protect the international rights of exiled and persecuted German and East European writers in the 1930s, and then in the fierce internal disagreements over whether PEN should defend the right to free expression of Nazi and Fascist collaborators such as Ezra Pound and Knut Hamsun. No less controversial was the organisations securing international financial and legal influence after acquiring consultative status to UNESCO and the UN in the late 1940s and its subsequent role in the cold war when a humanist internationalism became deeply politicised. The project aims to produce a comprehensive account of the organisation in order to understand what international free expression means today.