Project acronym ACCENT
Project Unravelling the architecture and the cartography of the human centriole
Researcher (PI) Paul, Philippe, Desiré GUICHARD
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Starting Grant (StG), LS1, ERC-2016-STG
Summary The centriole is the largest evolutionary conserved macromolecular structure responsible for building centrosomes and cilia or flagella in many eukaryotes. Centrioles are critical for the proper execution of important biological processes ranging from cell division to cell signaling. Moreover, centriolar defects have been associated to several human pathologies including ciliopathies and cancer. This state of facts emphasizes the importance of understanding centriole biogenesis. The study of centriole formation is a deep-rooted question, however our current knowledge on its molecular organization at high resolution remains fragmented and limited. In particular, exquisite details of the overall molecular architecture of the human centriole and in particular of its central core region are lacking to understand the basis of centriole organization and function. Resolving this important question represents a challenge that needs to be undertaken and will undoubtedly lead to groundbreaking advances. Another important question to tackle next is to develop innovative methods to enable the nanometric molecular mapping of centriolar proteins within distinct architectural elements of the centriole. This missing information will be key to unravel the molecular mechanisms behind centriolar organization.
This research proposal aims at building a cartography of the human centriole by elucidating its molecular composition and architecture. To this end, we will combine the use of innovative and multidisciplinary techniques encompassing spatial proteomics, cryo-electron tomography, state-of-the-art microscopy and in vitro assays and to achieve a comprehensive molecular and structural view of the human centriole. All together, we expect that these advances will help understand basic principles underlying centriole and cilia formation as well as might have further relevance for human health.
Summary
The centriole is the largest evolutionary conserved macromolecular structure responsible for building centrosomes and cilia or flagella in many eukaryotes. Centrioles are critical for the proper execution of important biological processes ranging from cell division to cell signaling. Moreover, centriolar defects have been associated to several human pathologies including ciliopathies and cancer. This state of facts emphasizes the importance of understanding centriole biogenesis. The study of centriole formation is a deep-rooted question, however our current knowledge on its molecular organization at high resolution remains fragmented and limited. In particular, exquisite details of the overall molecular architecture of the human centriole and in particular of its central core region are lacking to understand the basis of centriole organization and function. Resolving this important question represents a challenge that needs to be undertaken and will undoubtedly lead to groundbreaking advances. Another important question to tackle next is to develop innovative methods to enable the nanometric molecular mapping of centriolar proteins within distinct architectural elements of the centriole. This missing information will be key to unravel the molecular mechanisms behind centriolar organization.
This research proposal aims at building a cartography of the human centriole by elucidating its molecular composition and architecture. To this end, we will combine the use of innovative and multidisciplinary techniques encompassing spatial proteomics, cryo-electron tomography, state-of-the-art microscopy and in vitro assays and to achieve a comprehensive molecular and structural view of the human centriole. All together, we expect that these advances will help understand basic principles underlying centriole and cilia formation as well as might have further relevance for human health.
Max ERC Funding
1 498 965 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym ACTINONSRF
Project MAL: an actin-regulated SRF transcriptional coactivator
Researcher (PI) Richard Treisman
Host Institution (HI) THE FRANCIS CRICK INSTITUTE LIMITED
Call Details Advanced Grant (AdG), LS1, ERC-2010-AdG_20100317
Summary MAL: an actin-regulated SRF transcriptional coactivator
Recent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-binding MRTFs (MAL, Mkl2), which couple its activity to cytoskeletal dynamics, and the ERK-regulated TCFs (Elk-1, SAP-1, Net). MAL subcellular localisation and transcriptional activity responds to signal-induced changes in G-actin concentration, which are sensed by its actin-binding N-terminal RPEL domain. Members of a second family of RPEL proteins, the Phactrs, also exhibit actin-regulated nucleocytoplasmic shuttling. The proposal addresses the following novel features of actin biology:
¿ Actin as a transcriptional regulator
¿ Actin as a signalling molecule
¿ Actin-binding proteins as targets for regulation by actin, rather than regulators of actin function
We will analyse the sequences and proteins involved in actin-regulated nucleocytoplasmic shuttling, using structural biology and biochemistry to analyse its control by changes in actin-RPEL domain interactions. We will characterise the dynamics of shuttling, and develop reporters for changes in actin-MAL interaction for analysis of pathway activation in vivo. We will identify genes controlling MAL itself, and the balance between the nuclear and cytoplasmic actin pools. The mechanism by which actin represses transcriptional activation by MAL in the nucleus, and its relation to MAL phosphorylation, will be elucidated. Finally, we will map MRTF and TCF cofactor recruitment to SRF targets on a genome-wide scale, and identify the steps in transcription controlled by actin-MAL interaction.
Summary
MAL: an actin-regulated SRF transcriptional coactivator
Recent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-binding MRTFs (MAL, Mkl2), which couple its activity to cytoskeletal dynamics, and the ERK-regulated TCFs (Elk-1, SAP-1, Net). MAL subcellular localisation and transcriptional activity responds to signal-induced changes in G-actin concentration, which are sensed by its actin-binding N-terminal RPEL domain. Members of a second family of RPEL proteins, the Phactrs, also exhibit actin-regulated nucleocytoplasmic shuttling. The proposal addresses the following novel features of actin biology:
¿ Actin as a transcriptional regulator
¿ Actin as a signalling molecule
¿ Actin-binding proteins as targets for regulation by actin, rather than regulators of actin function
We will analyse the sequences and proteins involved in actin-regulated nucleocytoplasmic shuttling, using structural biology and biochemistry to analyse its control by changes in actin-RPEL domain interactions. We will characterise the dynamics of shuttling, and develop reporters for changes in actin-MAL interaction for analysis of pathway activation in vivo. We will identify genes controlling MAL itself, and the balance between the nuclear and cytoplasmic actin pools. The mechanism by which actin represses transcriptional activation by MAL in the nucleus, and its relation to MAL phosphorylation, will be elucidated. Finally, we will map MRTF and TCF cofactor recruitment to SRF targets on a genome-wide scale, and identify the steps in transcription controlled by actin-MAL interaction.
Max ERC Funding
1 889 995 €
Duration
Start date: 2011-10-01, End date: 2017-09-30
Project acronym AlgoFinance
Project Algorithmic Finance: Inquiring into the Reshaping of Financial Markets
Researcher (PI) Christian BORCH
Host Institution (HI) COPENHAGEN BUSINESS SCHOOL
Call Details Consolidator Grant (CoG), SH3, ERC-2016-COG
Summary Present-day financial markets are turning algorithmic, as market orders are increasingly being executed by fully automated computer algorithms, without any direct human intervention. Although algorithmic finance seems to fundamentally reshape the central dynamics in financial markets, and even though it prompts core sociological questions, it has not yet received any systematic attention. In a pioneering contribution to economic sociology and social studies of finance, ALGOFINANCE aims to understand how and with what consequences the turn to algorithms is changing financial markets. The overall concept and central contributions of ALGOFINANCE are the following: (1) on an intra-firm level, the project examines how the shift to algorithmic finance reshapes the ways in which trading firms operate, and does so by systematically and empirically investigating the reconfiguration of organizational structures and employee subjectivity; (2) on an inter-algorithmic level, it offers a ground-breaking methodology (agent-based modelling informed by qualitative data) to grasp how trading algorithms interact with one another in a fully digital space; and (3) on the level of market sociality, it proposes a novel theorization of how intra-firm and inter-algorithmic dynamics can be conceived of as introducing a particular form of sociality that is characteristic to algorithmic finance: a form of sociality-as-association heuristically analyzed as imitation. None of these three levels have received systematic attention in the state-of-the-art literature. Addressing them will significantly advance the understanding of present-day algorithmic finance in economic sociology. By contributing novel empirical, methodological, and theoretical understandings of the functioning and consequences of algorithms, ALGOFINANCE will pave the way for other research into digital sociology and the broader algorithmization of society.
Summary
Present-day financial markets are turning algorithmic, as market orders are increasingly being executed by fully automated computer algorithms, without any direct human intervention. Although algorithmic finance seems to fundamentally reshape the central dynamics in financial markets, and even though it prompts core sociological questions, it has not yet received any systematic attention. In a pioneering contribution to economic sociology and social studies of finance, ALGOFINANCE aims to understand how and with what consequences the turn to algorithms is changing financial markets. The overall concept and central contributions of ALGOFINANCE are the following: (1) on an intra-firm level, the project examines how the shift to algorithmic finance reshapes the ways in which trading firms operate, and does so by systematically and empirically investigating the reconfiguration of organizational structures and employee subjectivity; (2) on an inter-algorithmic level, it offers a ground-breaking methodology (agent-based modelling informed by qualitative data) to grasp how trading algorithms interact with one another in a fully digital space; and (3) on the level of market sociality, it proposes a novel theorization of how intra-firm and inter-algorithmic dynamics can be conceived of as introducing a particular form of sociality that is characteristic to algorithmic finance: a form of sociality-as-association heuristically analyzed as imitation. None of these three levels have received systematic attention in the state-of-the-art literature. Addressing them will significantly advance the understanding of present-day algorithmic finance in economic sociology. By contributing novel empirical, methodological, and theoretical understandings of the functioning and consequences of algorithms, ALGOFINANCE will pave the way for other research into digital sociology and the broader algorithmization of society.
Max ERC Funding
1 590 036 €
Duration
Start date: 2017-05-01, End date: 2021-04-30
Project acronym altEJrepair
Project Characterisation of DNA Double-Strand Break Repair by Alternative End-Joining: Potential Targets for Cancer Therapy
Researcher (PI) Raphael CECCALDI
Host Institution (HI) INSTITUT CURIE
Call Details Starting Grant (StG), LS1, ERC-2016-STG
Summary DNA repair pathways evolved as an intricate network that senses DNA damage and resolves it in order to minimise genetic lesions and thus preventing tumour formation. Gaining in recognition the last few years, the alternative end-joining (alt-EJ) DNA repair pathway was recently shown to be up-regulated and required for cancer cell viability in the absence of homologous recombination-mediated repair (HR). Despite this integral role, the alt-EJ repair pathway remains poorly characterised in humans. As such, its molecular composition, regulation and crosstalk with HR and other repair pathways remain elusive. Additionally, the contribution of the alt-EJ pathway to tumour progression as well as the identification of a mutational signature associated with the use of alt-EJ has not yet been investigated. Moreover, the clinical relevance of developing small-molecule inhibitors targeting players in the alt-EJ pathway, such as the polymerase Pol Theta (Polθ), is of importance as current anticancer drug treatments have shown limited effectiveness in achieving cancer remission in patients with HR-deficient (HRD) tumours.
Here, we propose a novel, multidisciplinary approach that aims to characterise the players and mechanisms of action involved in the utilisation of alt-EJ in cancer. This understanding will better elucidate the changing interplay between different DNA repair pathways, thus shedding light on whether and how the use of alt-EJ contributes to the pathogenic history and survival of HRD tumours, eventually paving the way for the development of novel anticancer therapeutics.
For all the abovementioned reasons, we are convinced this project will have important implications in: 1) elucidating critical interconnections between DNA repair pathways, 2) improving the basic understanding of the composition, regulation and function of the alt-EJ pathway, and 3) facilitating the development of new synthetic lethality-based chemotherapeutics for the treatment of HRD tumours.
Summary
DNA repair pathways evolved as an intricate network that senses DNA damage and resolves it in order to minimise genetic lesions and thus preventing tumour formation. Gaining in recognition the last few years, the alternative end-joining (alt-EJ) DNA repair pathway was recently shown to be up-regulated and required for cancer cell viability in the absence of homologous recombination-mediated repair (HR). Despite this integral role, the alt-EJ repair pathway remains poorly characterised in humans. As such, its molecular composition, regulation and crosstalk with HR and other repair pathways remain elusive. Additionally, the contribution of the alt-EJ pathway to tumour progression as well as the identification of a mutational signature associated with the use of alt-EJ has not yet been investigated. Moreover, the clinical relevance of developing small-molecule inhibitors targeting players in the alt-EJ pathway, such as the polymerase Pol Theta (Polθ), is of importance as current anticancer drug treatments have shown limited effectiveness in achieving cancer remission in patients with HR-deficient (HRD) tumours.
Here, we propose a novel, multidisciplinary approach that aims to characterise the players and mechanisms of action involved in the utilisation of alt-EJ in cancer. This understanding will better elucidate the changing interplay between different DNA repair pathways, thus shedding light on whether and how the use of alt-EJ contributes to the pathogenic history and survival of HRD tumours, eventually paving the way for the development of novel anticancer therapeutics.
For all the abovementioned reasons, we are convinced this project will have important implications in: 1) elucidating critical interconnections between DNA repair pathways, 2) improving the basic understanding of the composition, regulation and function of the alt-EJ pathway, and 3) facilitating the development of new synthetic lethality-based chemotherapeutics for the treatment of HRD tumours.
Max ERC Funding
1 498 750 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym ARCID
Project The Role of Arl Proteins in Retinal and other Ciliary Diseases
Researcher (PI) Alfred Wittinghofer
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS1, ERC-2010-AdG_20100317
Summary Arl (Arf-like) proteins, GTP-binding proteins of the Ras superfamily, are molecular switches that cycle between a GDP-bound inactive and GTP-bound active state. There are 16 members of the Arl subfamily in the human genome whose basic mechanistic function is unknown. The interactome of Arl2/3 includes proteins involved in retinopathies and other ciliary diseases such as Leber¿s Congenital Amaurosis (LCA) and kidney diseases such as nephronophthisis. Arl6 has been found mutated in Bardet Biedl Syndrome, another pleiotropic ciliary disease. In the proposed interdisciplinary project I want to explore the function of the protein network of Arl2/3 and Arl6 by a combination of biochemical, biophysical and structural methods and use the knowledge obtained to probe their function in live cells. As with other subfamily proteins of the Ras superfamily which have been found to mediate similar biological functions I want to derive a basic understanding of the function of Arl proteins and how it relates to the development and function of the ciliary organelle and how they contribute to ciliary diseases. The molecules in the focus of the project are: the GTP-binding proteins Arl2, 3, 6; RP2, an Arl3GAP mutated in Retinitis pigmentosa; Regulators of Arl2 and 3; PDE¿ and HRG4, effectors of Arl2/3, which bind lipidated proteins; RPGR, mutated in Retinitis pigmentosa, an interactor of PDE¿; RPGRIP and RPGRIPL, interactors of RPGR mutated in LCA and other ciliopathies; Nephrocystin, mutated in nephronophthisis, an interactor of RPGRIP and Arl6, mutated in Bardet Biedl Syndrome, and the BBS complex. The working hypothesis is that Arl protein network(s) mediate ciliary transport processes and that the GTP switch cycle of Arl proteins is an important element of regulation of these processes.
Summary
Arl (Arf-like) proteins, GTP-binding proteins of the Ras superfamily, are molecular switches that cycle between a GDP-bound inactive and GTP-bound active state. There are 16 members of the Arl subfamily in the human genome whose basic mechanistic function is unknown. The interactome of Arl2/3 includes proteins involved in retinopathies and other ciliary diseases such as Leber¿s Congenital Amaurosis (LCA) and kidney diseases such as nephronophthisis. Arl6 has been found mutated in Bardet Biedl Syndrome, another pleiotropic ciliary disease. In the proposed interdisciplinary project I want to explore the function of the protein network of Arl2/3 and Arl6 by a combination of biochemical, biophysical and structural methods and use the knowledge obtained to probe their function in live cells. As with other subfamily proteins of the Ras superfamily which have been found to mediate similar biological functions I want to derive a basic understanding of the function of Arl proteins and how it relates to the development and function of the ciliary organelle and how they contribute to ciliary diseases. The molecules in the focus of the project are: the GTP-binding proteins Arl2, 3, 6; RP2, an Arl3GAP mutated in Retinitis pigmentosa; Regulators of Arl2 and 3; PDE¿ and HRG4, effectors of Arl2/3, which bind lipidated proteins; RPGR, mutated in Retinitis pigmentosa, an interactor of PDE¿; RPGRIP and RPGRIPL, interactors of RPGR mutated in LCA and other ciliopathies; Nephrocystin, mutated in nephronophthisis, an interactor of RPGRIP and Arl6, mutated in Bardet Biedl Syndrome, and the BBS complex. The working hypothesis is that Arl protein network(s) mediate ciliary transport processes and that the GTP switch cycle of Arl proteins is an important element of regulation of these processes.
Max ERC Funding
2 434 400 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym ARGO
Project The Quest of the Argonautes - from Myth to Reality
Researcher (PI) JOHN VAN DER OOST
Host Institution (HI) WAGENINGEN UNIVERSITY
Call Details Advanced Grant (AdG), LS1, ERC-2018-ADG
Summary Argonaute nucleases are key players of the eukaryotic RNA interference (RNAi) system. Using small RNA guides, these Argonaute (Ago) proteins specifically target complementary RNA molecules, resulting in regulation of a wide range of crucial processes, including chromosome organization, gene expression and anti-virus defence. Since 2010, my research team has studied closely-related prokaryotic Argonaute (pAgo) variants. This has revealed spectacular mechanistic variations: several thermophilic pAgos catalyse DNA-guided cleavage of double stranded DNA, but only at elevated temperatures. Interestingly, a recently discovered mesophilic Argonaute (CbAgo) can generate double strand DNA breaks at moderate temperatures, providing an excellent basis for this ARGO project. In addition, genome analysis has revealed many distantly-related Argonaute variants, often with unique domain architectures. Hence, the currently known Argonaute homologs are just the tip of the iceberg, and the stage is set for making a big leap in the exploration of the Argonaute family. Initially we will dissect the molecular basis of functional and mechanistic features of uncharacterized natural Argonaute variants, both in eukaryotes (the presence of an Ago-like subunit in the Mediator complex, strongly suggests a regulatory role of an elusive non-coding RNA ligand) and in prokaryotes (selected Ago variants possess distinct domains indicating novel functionalities). After their thorough biochemical characterization, I aim at engineering the functionality of the aforementioned CbAgo through an integrated rational & random approach, i.e. by tinkering of domains, and by an unprecedented in vitro laboratory evolution approach. Eventually, natural & synthetic Argonautes will be selected for their exploitation, and used for developing original genome editing applications (from silencing to base editing). Embarking on this ambitious ARGO expedition will lead us to many exciting discoveries.
Summary
Argonaute nucleases are key players of the eukaryotic RNA interference (RNAi) system. Using small RNA guides, these Argonaute (Ago) proteins specifically target complementary RNA molecules, resulting in regulation of a wide range of crucial processes, including chromosome organization, gene expression and anti-virus defence. Since 2010, my research team has studied closely-related prokaryotic Argonaute (pAgo) variants. This has revealed spectacular mechanistic variations: several thermophilic pAgos catalyse DNA-guided cleavage of double stranded DNA, but only at elevated temperatures. Interestingly, a recently discovered mesophilic Argonaute (CbAgo) can generate double strand DNA breaks at moderate temperatures, providing an excellent basis for this ARGO project. In addition, genome analysis has revealed many distantly-related Argonaute variants, often with unique domain architectures. Hence, the currently known Argonaute homologs are just the tip of the iceberg, and the stage is set for making a big leap in the exploration of the Argonaute family. Initially we will dissect the molecular basis of functional and mechanistic features of uncharacterized natural Argonaute variants, both in eukaryotes (the presence of an Ago-like subunit in the Mediator complex, strongly suggests a regulatory role of an elusive non-coding RNA ligand) and in prokaryotes (selected Ago variants possess distinct domains indicating novel functionalities). After their thorough biochemical characterization, I aim at engineering the functionality of the aforementioned CbAgo through an integrated rational & random approach, i.e. by tinkering of domains, and by an unprecedented in vitro laboratory evolution approach. Eventually, natural & synthetic Argonautes will be selected for their exploitation, and used for developing original genome editing applications (from silencing to base editing). Embarking on this ambitious ARGO expedition will lead us to many exciting discoveries.
Max ERC Funding
2 177 158 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym ASSHURED
Project Analysing South-South Humanitarian Responses to Displacement from Syria: Views from Lebanon, Jordan and Turkey
Researcher (PI) Elena FIDDIAN-QASMIYEH
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Starting Grant (StG), SH3, ERC-2016-STG
Summary Since 2012, over 4 million people have fled Syria in ‘the most dramatic humanitarian crisis that we have ever faced’ (UNHCR). By November 2015 there were 1,078,338 refugees from Syria in Lebanon, 630,776 in Jordan and 2,181,293 in Turkey. Humanitarian agencies and donor states from both the global North and the global South have funded and implemented aid programmes, and yet commentators have argued that civil society groups from the global South are the most significant actors supporting refugees in Lebanon, Jordan and Turkey. Whilst they are highly significant responses, however, major gaps in knowledge remain regarding the motivations, nature and implications of Southern-led responses to conflict-induced displacement. This project draws on multi-sited ethnographic and participatory research with refugees from Syria and their aid providers in Lebanon, Jordan and Turkey to critically examine why, how and with what effect actors from the South have responded to the displacement of refugees from Syria. The main research aims are:
1. identifying diverse models of Southern-led responses to conflict-induced displacement,
2. examining the (un)official motivations, nature and implications of Southern-led responses,
3. examining refugees’ experiences and perceptions of Southern-led responses,
4. exploring diverse Southern and Northern actors’ perceptions of Southern-led responses,
5. tracing the implications of Southern-led initiatives for humanitarian theory and practice.
Based on a critical theoretical framework inspired by post-colonial and feminist approaches, the project contributes to theories of humanitarianism and debates regarding donor-recipient relations and refugees’ agency in displacement situations. It will also inform the development of policies to most appropriately address refugees’ needs and rights. This highly topical and innovative project thus has far-reaching implications for refugees and local communities, academics, policy-makers and practitioners.
Summary
Since 2012, over 4 million people have fled Syria in ‘the most dramatic humanitarian crisis that we have ever faced’ (UNHCR). By November 2015 there were 1,078,338 refugees from Syria in Lebanon, 630,776 in Jordan and 2,181,293 in Turkey. Humanitarian agencies and donor states from both the global North and the global South have funded and implemented aid programmes, and yet commentators have argued that civil society groups from the global South are the most significant actors supporting refugees in Lebanon, Jordan and Turkey. Whilst they are highly significant responses, however, major gaps in knowledge remain regarding the motivations, nature and implications of Southern-led responses to conflict-induced displacement. This project draws on multi-sited ethnographic and participatory research with refugees from Syria and their aid providers in Lebanon, Jordan and Turkey to critically examine why, how and with what effect actors from the South have responded to the displacement of refugees from Syria. The main research aims are:
1. identifying diverse models of Southern-led responses to conflict-induced displacement,
2. examining the (un)official motivations, nature and implications of Southern-led responses,
3. examining refugees’ experiences and perceptions of Southern-led responses,
4. exploring diverse Southern and Northern actors’ perceptions of Southern-led responses,
5. tracing the implications of Southern-led initiatives for humanitarian theory and practice.
Based on a critical theoretical framework inspired by post-colonial and feminist approaches, the project contributes to theories of humanitarianism and debates regarding donor-recipient relations and refugees’ agency in displacement situations. It will also inform the development of policies to most appropriately address refugees’ needs and rights. This highly topical and innovative project thus has far-reaching implications for refugees and local communities, academics, policy-makers and practitioners.
Max ERC Funding
1 498 069 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym BAM
Project Becoming A Minority
Researcher (PI) Maurice CRUL
Host Institution (HI) STICHTING VU
Call Details Advanced Grant (AdG), SH3, ERC-2016-ADG
Summary In the last forty years, researchers in the Field of Migration and Ethnic Studies looked at the integration of migrants and their descendants. Concepts, methodological tools and theoretical frameworks have been developed to measure and predict integration outcomes both across different ethnic groups and in comparison with people of native descent. But are we also looking into the actual integration of the receiving group of native ‘white’ descent in city contexts where they have become a numerical minority themselves? In cities like Amsterdam, now only one in three youngsters under age fifteen is of native descent. This situation, referred to as a majority-minority context, is a new phenomenon in Western Europe and it presents itself as one of the most important societal and psychological transformations of our time. I argue that the field of migration and ethnic studies is stagnating because of the one-sided focus on migrants and their children. This is even more urgent given the increased ant-immigrant vote. These pressing scientific and societal reasons pushed me to develop the project BAM (Becoming A Minority). The project will be executed in three harbor cities, Rotterdam, Antwerp and Malmö, and three service sector cities, Amsterdam, Frankfurt and Vienna. BAM consists of 5 subprojects: (1) A meta-analysis of secondary data on people of native ‘white’ descent in the six research sites; (2) A newly developed survey for the target group; (3) An analysis of critical circumstances of encounter that trigger either positive or rather negative responses to increased ethnic diversity (4) Experimental diversity labs to test under which circumstances people will change their attitudes or their actions towards increased ethnic diversity; (5) The formulation of a new theory of integration that includes the changed position of the group of native ‘white’ descent as an important actor.
Summary
In the last forty years, researchers in the Field of Migration and Ethnic Studies looked at the integration of migrants and their descendants. Concepts, methodological tools and theoretical frameworks have been developed to measure and predict integration outcomes both across different ethnic groups and in comparison with people of native descent. But are we also looking into the actual integration of the receiving group of native ‘white’ descent in city contexts where they have become a numerical minority themselves? In cities like Amsterdam, now only one in three youngsters under age fifteen is of native descent. This situation, referred to as a majority-minority context, is a new phenomenon in Western Europe and it presents itself as one of the most important societal and psychological transformations of our time. I argue that the field of migration and ethnic studies is stagnating because of the one-sided focus on migrants and their children. This is even more urgent given the increased ant-immigrant vote. These pressing scientific and societal reasons pushed me to develop the project BAM (Becoming A Minority). The project will be executed in three harbor cities, Rotterdam, Antwerp and Malmö, and three service sector cities, Amsterdam, Frankfurt and Vienna. BAM consists of 5 subprojects: (1) A meta-analysis of secondary data on people of native ‘white’ descent in the six research sites; (2) A newly developed survey for the target group; (3) An analysis of critical circumstances of encounter that trigger either positive or rather negative responses to increased ethnic diversity (4) Experimental diversity labs to test under which circumstances people will change their attitudes or their actions towards increased ethnic diversity; (5) The formulation of a new theory of integration that includes the changed position of the group of native ‘white’ descent as an important actor.
Max ERC Funding
2 499 714 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym BAPS
Project Bayesian Agent-based Population Studies: Transforming Simulation Models of Human Migration
Researcher (PI) Jakub KAZIMIERZ BIJAK
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Call Details Consolidator Grant (CoG), SH3, ERC-2016-COG
Summary The aim of BAPS is to develop a ground-breaking simulation model of international migration, based on a population of intelligent, cognitive agents, their social networks and institutions, all interacting with one another. The project will transform the study of migration – one of the most uncertain population processes and a top-priority EU policy area – by offering a step change in the way it can be understood, predicted and managed. In this way, BAPS will effectively integrate behavioural and social theory with modelling.
To develop micro-foundations for migration studies, model design will follow cutting-edge developments in demography, statistics, cognitive psychology and computer science. BAPS will also offer a pioneering environment for applying the findings in practice through a bespoke modelling language. Bayesian statistical principles will be used to design innovative computer experiments, and learn about modelling the simulated individuals and the way they make decisions.
In BAPS, we will collate available information for migration models; build and test the simulations by applying experimental design principles to enhance our knowledge of migration processes; collect information on the underpinning decision-making mechanisms through psychological experiments; and design software for implementing Bayesian agent-based models in practice. The project will use various information sources to build models bottom-up, filling an important epistemological gap in demography.
BAPS will be carried out by the Allianz European Demographer 2015, recognised as a leader in the field for methodological innovation, directing an interdisciplinary team with expertise in demography, agent-based models, statistical analysis of uncertainty, meta-cognition, and computer simulations. The project will open up exciting research possibilities beyond demography, and will generate both academic and practical impact, offering methodological advice for policy-relevant simulations.
Summary
The aim of BAPS is to develop a ground-breaking simulation model of international migration, based on a population of intelligent, cognitive agents, their social networks and institutions, all interacting with one another. The project will transform the study of migration – one of the most uncertain population processes and a top-priority EU policy area – by offering a step change in the way it can be understood, predicted and managed. In this way, BAPS will effectively integrate behavioural and social theory with modelling.
To develop micro-foundations for migration studies, model design will follow cutting-edge developments in demography, statistics, cognitive psychology and computer science. BAPS will also offer a pioneering environment for applying the findings in practice through a bespoke modelling language. Bayesian statistical principles will be used to design innovative computer experiments, and learn about modelling the simulated individuals and the way they make decisions.
In BAPS, we will collate available information for migration models; build and test the simulations by applying experimental design principles to enhance our knowledge of migration processes; collect information on the underpinning decision-making mechanisms through psychological experiments; and design software for implementing Bayesian agent-based models in practice. The project will use various information sources to build models bottom-up, filling an important epistemological gap in demography.
BAPS will be carried out by the Allianz European Demographer 2015, recognised as a leader in the field for methodological innovation, directing an interdisciplinary team with expertise in demography, agent-based models, statistical analysis of uncertainty, meta-cognition, and computer simulations. The project will open up exciting research possibilities beyond demography, and will generate both academic and practical impact, offering methodological advice for policy-relevant simulations.
Max ERC Funding
1 455 590 €
Duration
Start date: 2017-06-01, End date: 2021-05-31
Project acronym BENDER
Project BiogENesis and Degradation of Endoplasmic Reticulum proteins
Researcher (PI) Friedrich Förster
Host Institution (HI) UNIVERSITEIT UTRECHT
Call Details Consolidator Grant (CoG), LS1, ERC-2016-COG
Summary The Endoplasmic Reticulum (ER) membrane in all eukaryotic cells has an intricate protein network that facilitates protein biogene-sis and homeostasis. The molecular complexity and sophisticated regulation of this machinery favours study-ing it in its native microenvironment by novel approaches. Cryo-electron tomography (CET) allows 3D im-aging of membrane-associated complexes in their native surrounding. Computational analysis of many sub-tomograms depicting the same type of macromolecule, a technology I pioneered, provides subnanometer resolution insights into different conformations of native complexes.
I propose to leverage CET of cellular and cell-free systems to reveal the molecular details of ER protein bio-genesis and homeostasis. In detail, I will study: (a) The structure of the ER translocon, the dynamic gateway for import of nascent proteins into the ER and their maturation. The largest component is the oligosaccharyl transferase complex. (b) Cotranslational ER import, N-glycosylation, chaperone-mediated stabilization and folding as well as oligomerization of established model substrate such a major histocompatibility complex (MHC) class I and II complexes. (c) The degradation of misfolded ER-residing proteins by the cytosolic 26S proteasome using cytomegalovirus-induced depletion of MHC class I as a model system. (d) The structural changes of the ER-bound translation machinery upon ER stress through IRE1-mediated degradation of mRNA that is specific for ER-targeted proteins. (e) The improved ‘in silico purification’ of different states of native macromolecules by maximum likelihood subtomogram classification and its application to a-d.
This project will be the blueprint for a new approach to structural biology of membrane-associated processes. It will contribute to our mechanistic understanding of viral immune evasion and glycosylation disorders as well as numerous diseases involving chronic ER stress including diabetes and neurodegenerative diseases.
Summary
The Endoplasmic Reticulum (ER) membrane in all eukaryotic cells has an intricate protein network that facilitates protein biogene-sis and homeostasis. The molecular complexity and sophisticated regulation of this machinery favours study-ing it in its native microenvironment by novel approaches. Cryo-electron tomography (CET) allows 3D im-aging of membrane-associated complexes in their native surrounding. Computational analysis of many sub-tomograms depicting the same type of macromolecule, a technology I pioneered, provides subnanometer resolution insights into different conformations of native complexes.
I propose to leverage CET of cellular and cell-free systems to reveal the molecular details of ER protein bio-genesis and homeostasis. In detail, I will study: (a) The structure of the ER translocon, the dynamic gateway for import of nascent proteins into the ER and their maturation. The largest component is the oligosaccharyl transferase complex. (b) Cotranslational ER import, N-glycosylation, chaperone-mediated stabilization and folding as well as oligomerization of established model substrate such a major histocompatibility complex (MHC) class I and II complexes. (c) The degradation of misfolded ER-residing proteins by the cytosolic 26S proteasome using cytomegalovirus-induced depletion of MHC class I as a model system. (d) The structural changes of the ER-bound translation machinery upon ER stress through IRE1-mediated degradation of mRNA that is specific for ER-targeted proteins. (e) The improved ‘in silico purification’ of different states of native macromolecules by maximum likelihood subtomogram classification and its application to a-d.
This project will be the blueprint for a new approach to structural biology of membrane-associated processes. It will contribute to our mechanistic understanding of viral immune evasion and glycosylation disorders as well as numerous diseases involving chronic ER stress including diabetes and neurodegenerative diseases.
Max ERC Funding
2 496 611 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
