Project acronym ACROSS
Project Australasian Colonization Research: Origins of Seafaring to Sahul
Researcher (PI) Rosemary Helen FARR
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Country United Kingdom
Call Details Starting Grant (StG), SH6, ERC-2017-STG
Summary One of the most exciting research questions within archaeology is that of the peopling of Australasia by at least c.50,000 years ago. This represents some of the earliest evidence of modern human colonization outside Africa, yet, even at the greatest sea-level lowstand, this migration would have involved seafaring. It is the maritime nature of this dispersal which makes it so important to questions of technological, cognitive and social human development. These issues have traditionally been the preserve of archaeologists, but with a multidisciplinary approach that embraces cutting-edge marine geophysical, hydrodynamic and archaeogenetic analyses, we now have the opportunity to examine the When, Where, Who and How of the earliest seafaring in world history.
The voyage from Sunda (South East Asia) to Sahul (Australasia) provides evidence for the earliest ‘open water’ crossing in the world. A combination of the sparse number of early archaeological finds and the significant changes in the palaeolandscape and submergence of the broad north western Australian continental shelf, mean that little is known about the routes taken and what these crossings may have entailed.
This project will combine research of the submerged palaeolandscape of the continental shelf to refine our knowledge of the onshore/offshore environment, identify potential submerged prehistoric sites and enhance our understanding of the palaeoshoreline and tidal regime. This will be combined with archaeogenetic research targeting mtDNA and Y-chromosome data to resolve questions of demography and dating.
For the first time this project takes a truly multidisciplinary approach to address the colonization of Sahul, providing an unique opportunity to tackle some of the most important questions about human origins, the relationship between humans and the changing environment, population dynamics and migration, seafaring technology, social organisation and cognition.
Summary
One of the most exciting research questions within archaeology is that of the peopling of Australasia by at least c.50,000 years ago. This represents some of the earliest evidence of modern human colonization outside Africa, yet, even at the greatest sea-level lowstand, this migration would have involved seafaring. It is the maritime nature of this dispersal which makes it so important to questions of technological, cognitive and social human development. These issues have traditionally been the preserve of archaeologists, but with a multidisciplinary approach that embraces cutting-edge marine geophysical, hydrodynamic and archaeogenetic analyses, we now have the opportunity to examine the When, Where, Who and How of the earliest seafaring in world history.
The voyage from Sunda (South East Asia) to Sahul (Australasia) provides evidence for the earliest ‘open water’ crossing in the world. A combination of the sparse number of early archaeological finds and the significant changes in the palaeolandscape and submergence of the broad north western Australian continental shelf, mean that little is known about the routes taken and what these crossings may have entailed.
This project will combine research of the submerged palaeolandscape of the continental shelf to refine our knowledge of the onshore/offshore environment, identify potential submerged prehistoric sites and enhance our understanding of the palaeoshoreline and tidal regime. This will be combined with archaeogenetic research targeting mtDNA and Y-chromosome data to resolve questions of demography and dating.
For the first time this project takes a truly multidisciplinary approach to address the colonization of Sahul, providing an unique opportunity to tackle some of the most important questions about human origins, the relationship between humans and the changing environment, population dynamics and migration, seafaring technology, social organisation and cognition.
Max ERC Funding
1 134 928 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym AfricanNeo
Project The African Neolithic: A genetic perspective
Researcher (PI) Carina SCHLEBUSCH
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), SH6, ERC-2017-STG
Summary The spread of farming practices in various parts of the world had a marked influence on how humans live today and how we are distributed around the globe. Around 10,000 years ago, warmer conditions lead to population increases, coinciding with the invention of farming in several places around the world. Archaeological evidence attest to the spread of these practices to neighboring regions. In many cases this lead to whole continents being converted from hunter-gatherer to farming societies. It is however difficult to see from archaeological records if only the farming culture spread to other places or whether the farming people themselves migrated. Investigating patterns of genetic variation for farming populations and for remaining hunter-gatherer groups can help to resolve questions on population movements co-occurring with the spread of farming practices. It can further shed light on the routes of migration and dates when migrants arrived.
The spread of farming to Europe has been thoroughly investigated in the fields of archaeology, linguistics and genetics, while on other continents these events have been less investigated. In Africa, mainly linguistic and archaeological studies have attempted to elucidate the spread of farming and herding practices. I propose to investigate the movement of farmer and pastoral groups in Africa, by typing densely spaced genome-wide variant positions in a large number of African populations. The data will be used to infer how farming and pastoralism was introduced to various regions, where the incoming people originated from and when these (potential) population movements occurred. Through this study, the Holocene history of Africa will be revealed and placed into a global context of migration, mobility and cultural transitions. Additionally the study will give due credence to one of the largest Neolithic expansion events, the Bantu-expansion, which caused a pronounced change in the demographic landscape of the African continent
Summary
The spread of farming practices in various parts of the world had a marked influence on how humans live today and how we are distributed around the globe. Around 10,000 years ago, warmer conditions lead to population increases, coinciding with the invention of farming in several places around the world. Archaeological evidence attest to the spread of these practices to neighboring regions. In many cases this lead to whole continents being converted from hunter-gatherer to farming societies. It is however difficult to see from archaeological records if only the farming culture spread to other places or whether the farming people themselves migrated. Investigating patterns of genetic variation for farming populations and for remaining hunter-gatherer groups can help to resolve questions on population movements co-occurring with the spread of farming practices. It can further shed light on the routes of migration and dates when migrants arrived.
The spread of farming to Europe has been thoroughly investigated in the fields of archaeology, linguistics and genetics, while on other continents these events have been less investigated. In Africa, mainly linguistic and archaeological studies have attempted to elucidate the spread of farming and herding practices. I propose to investigate the movement of farmer and pastoral groups in Africa, by typing densely spaced genome-wide variant positions in a large number of African populations. The data will be used to infer how farming and pastoralism was introduced to various regions, where the incoming people originated from and when these (potential) population movements occurred. Through this study, the Holocene history of Africa will be revealed and placed into a global context of migration, mobility and cultural transitions. Additionally the study will give due credence to one of the largest Neolithic expansion events, the Bantu-expansion, which caused a pronounced change in the demographic landscape of the African continent
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym AfricanWomen
Project Women in Africa
Researcher (PI) catherine GUIRKINGER
Host Institution (HI) UNIVERSITE DE NAMUR ASBL
Country Belgium
Call Details Starting Grant (StG), SH1, ERC-2017-STG
Summary Rates of domestic violence and the relative risk of premature death for women are higher in sub-Saharan Africa than in any other region. Yet we know remarkably little about the economic forces, incentives and constraints that drive discrimination against women in this region, making it hard to identify policy levers to address the problem. This project will help fill this gap.
I will investigate gender discrimination from two complementary perspectives. First, through the lens of economic history, I will investigate the forces driving trends in women’s relative well-being since slavery. To quantify the evolution of well-being of sub-Saharan women relative to men, I will use three types of historical data: anthropometric indicators (relative height), vital statistics (to compute numbers of missing women), and outcomes of formal and informal family law disputes. I will then investigate how major economic developments and changes in family laws differentially affected women’s welfare across ethnic groups with different norms on women’s roles and rights.
Second, using intra-household economic models, I will provide new insights into domestic violence and gender bias in access to crucial resources in present-day Africa. I will develop a new household model that incorporates gender identity and endogenous outside options to explore the relationship between women’s empowerment and the use of violence. Using the notion of strategic delegation, I will propose a new rationale for the separation of budgets often observed in African households and generate predictions of how improvements in women’s outside options affect welfare. Finally, with first hand data, I will investigate intra-household differences in nutrition and work effort in times of food shortage from the points of view of efficiency and equity. I will use activity trackers as an innovative means of collecting high quality data on work effort and thus overcome data limitations restricting the existing literature
Summary
Rates of domestic violence and the relative risk of premature death for women are higher in sub-Saharan Africa than in any other region. Yet we know remarkably little about the economic forces, incentives and constraints that drive discrimination against women in this region, making it hard to identify policy levers to address the problem. This project will help fill this gap.
I will investigate gender discrimination from two complementary perspectives. First, through the lens of economic history, I will investigate the forces driving trends in women’s relative well-being since slavery. To quantify the evolution of well-being of sub-Saharan women relative to men, I will use three types of historical data: anthropometric indicators (relative height), vital statistics (to compute numbers of missing women), and outcomes of formal and informal family law disputes. I will then investigate how major economic developments and changes in family laws differentially affected women’s welfare across ethnic groups with different norms on women’s roles and rights.
Second, using intra-household economic models, I will provide new insights into domestic violence and gender bias in access to crucial resources in present-day Africa. I will develop a new household model that incorporates gender identity and endogenous outside options to explore the relationship between women’s empowerment and the use of violence. Using the notion of strategic delegation, I will propose a new rationale for the separation of budgets often observed in African households and generate predictions of how improvements in women’s outside options affect welfare. Finally, with first hand data, I will investigate intra-household differences in nutrition and work effort in times of food shortage from the points of view of efficiency and equity. I will use activity trackers as an innovative means of collecting high quality data on work effort and thus overcome data limitations restricting the existing literature
Max ERC Funding
1 499 313 €
Duration
Start date: 2018-08-01, End date: 2023-07-31
Project acronym Aftermath
Project THE AFTERMATH OF THE EAST ASIAN WAR OF 1592-1598.
Researcher (PI) Rebekah CLEMENTS
Host Institution (HI) UNIVERSIDAD AUTONOMA DE BARCELONA
Country Spain
Call Details Starting Grant (StG), SH6, ERC-2017-STG
Summary Aftermath seeks to understand the legacy of the East Asian War of 1592-1598. This conflict involved over 500,000 combatants from Japan, China, and Korea; up to 100,000 Korean civilians were abducted to Japan. The war caused momentous demographic upheaval and widespread destruction, but also had long-lasting cultural impact as a result of the removal to Japan of Korean technology and skilled labourers. The conflict and its aftermath bear striking parallels to events in East Asia during World War 2, and memories of the 16th century war remain deeply resonant in the region. However, the war and its immediate aftermath are also significant because they occurred at the juncture of periods often characterized as “medieval” and “early modern” in the East Asian case. What were the implications for the social, economic, and cultural contours of early modern East Asia? What can this conflict tell us about war “aftermath” across historical periods and about such periodization itself? There is little Western scholarship on the war and few studies in any language cross linguistic, disciplinary, and national boundaries to achieve a regional perspective that reflects the interconnected history of East Asia. Aftermath will radically alter our understanding of the region’s history by providing the first analysis of the state of East Asia as a result of the war. The focus will be on the period up to the middle of the 17th century, but not precluding ongoing effects. The team, with expertise covering Japan, Korea, and China, will investigate three themes: the movement of people and demographic change, the impact on the natural environment, and technological diffusion. The project will be the first large scale investigation to use Japanese, Korean, and Chinese sources to understand the war’s aftermath. It will broaden understandings of the early modern world, and push the boundaries of war legacy studies by exploring the meanings of “aftermath” in the early modern East Asian context.
Summary
Aftermath seeks to understand the legacy of the East Asian War of 1592-1598. This conflict involved over 500,000 combatants from Japan, China, and Korea; up to 100,000 Korean civilians were abducted to Japan. The war caused momentous demographic upheaval and widespread destruction, but also had long-lasting cultural impact as a result of the removal to Japan of Korean technology and skilled labourers. The conflict and its aftermath bear striking parallels to events in East Asia during World War 2, and memories of the 16th century war remain deeply resonant in the region. However, the war and its immediate aftermath are also significant because they occurred at the juncture of periods often characterized as “medieval” and “early modern” in the East Asian case. What were the implications for the social, economic, and cultural contours of early modern East Asia? What can this conflict tell us about war “aftermath” across historical periods and about such periodization itself? There is little Western scholarship on the war and few studies in any language cross linguistic, disciplinary, and national boundaries to achieve a regional perspective that reflects the interconnected history of East Asia. Aftermath will radically alter our understanding of the region’s history by providing the first analysis of the state of East Asia as a result of the war. The focus will be on the period up to the middle of the 17th century, but not precluding ongoing effects. The team, with expertise covering Japan, Korea, and China, will investigate three themes: the movement of people and demographic change, the impact on the natural environment, and technological diffusion. The project will be the first large scale investigation to use Japanese, Korean, and Chinese sources to understand the war’s aftermath. It will broaden understandings of the early modern world, and push the boundaries of war legacy studies by exploring the meanings of “aftermath” in the early modern East Asian context.
Max ERC Funding
1 444 980 €
Duration
Start date: 2018-11-01, End date: 2024-04-30
Project acronym AGEnTh
Project Atomic Gauge and Entanglement Theories
Researcher (PI) Marcello DALMONTE
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Country Italy
Call Details Starting Grant (StG), PE2, ERC-2017-STG
Summary AGEnTh is an interdisciplinary proposal which aims at theoretically investigating atomic many-body systems (cold atoms and trapped ions) in close connection to concepts from quantum information, condensed matter, and high energy physics. The main goals of this programme are to:
I) Find to scalable schemes for the measurements of entanglement properties, and in particular entanglement spectra, by proposing a shifting paradigm to access entanglement focused on entanglement Hamiltonians and field theories instead of probing density matrices;
II) Show how atomic gauge theories (including dynamical gauge fields) are ideal candidates for the realization of long-sought, highly-entangled states of matter, in particular topological superconductors supporting parafermion edge modes, and novel classes of quantum spin liquids emerging from clustering;
III) Develop new implementation strategies for the realization of gauge symmetries of paramount importance, such as discrete and SU(N)xSU(2)xU(1) groups, and establish a theoretical framework for the understanding of atomic physics experiments within the light-from-chaos scenario pioneered in particle physics.
These objectives are at the cutting-edge of fundamental science, and represent a coherent effort aimed at underpinning unprecedented regimes of strongly interacting quantum matter by addressing the basic aspects of probing, many-body physics, and implementations. The results are expected to (i) build up and establish qualitatively new synergies between the aforementioned communities, and (ii) stimulate an intense theoretical and experimental activity focused on both entanglement and atomic gauge theories.
In order to achieve those, AGEnTh builds: (1) on my background working at the interface between atomic physics and quantum optics from one side, and many-body theory on the other, and (2) on exploratory studies which I carried out to mitigate the conceptual risks associated with its high-risk/high-gain goals.
Summary
AGEnTh is an interdisciplinary proposal which aims at theoretically investigating atomic many-body systems (cold atoms and trapped ions) in close connection to concepts from quantum information, condensed matter, and high energy physics. The main goals of this programme are to:
I) Find to scalable schemes for the measurements of entanglement properties, and in particular entanglement spectra, by proposing a shifting paradigm to access entanglement focused on entanglement Hamiltonians and field theories instead of probing density matrices;
II) Show how atomic gauge theories (including dynamical gauge fields) are ideal candidates for the realization of long-sought, highly-entangled states of matter, in particular topological superconductors supporting parafermion edge modes, and novel classes of quantum spin liquids emerging from clustering;
III) Develop new implementation strategies for the realization of gauge symmetries of paramount importance, such as discrete and SU(N)xSU(2)xU(1) groups, and establish a theoretical framework for the understanding of atomic physics experiments within the light-from-chaos scenario pioneered in particle physics.
These objectives are at the cutting-edge of fundamental science, and represent a coherent effort aimed at underpinning unprecedented regimes of strongly interacting quantum matter by addressing the basic aspects of probing, many-body physics, and implementations. The results are expected to (i) build up and establish qualitatively new synergies between the aforementioned communities, and (ii) stimulate an intense theoretical and experimental activity focused on both entanglement and atomic gauge theories.
In order to achieve those, AGEnTh builds: (1) on my background working at the interface between atomic physics and quantum optics from one side, and many-body theory on the other, and (2) on exploratory studies which I carried out to mitigate the conceptual risks associated with its high-risk/high-gain goals.
Max ERC Funding
1 055 317 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym ALGOCom
Project Novel Algorithmic Techniques through the Lens of Combinatorics
Researcher (PI) Parinya Chalermsook
Host Institution (HI) AALTO KORKEAKOULUSAATIO SR
Country Finland
Call Details Starting Grant (StG), PE6, ERC-2017-STG
Summary Real-world optimization problems pose major challenges to algorithmic research. For instance, (i) many important problems are believed to be intractable (i.e. NP-hard) and (ii) with the growth of data size, modern applications often require a decision making under {\em incomplete and dynamically changing input data}. After several decades of research, central problems in these domains have remained poorly understood (e.g. Is there an asymptotically most efficient binary search trees?) Existing algorithmic techniques either reach their limitation or are inherently tailored to special cases.
This project attempts to untangle this gap in the state of the art and seeks new interplay across multiple areas of algorithms, such as approximation algorithms, online algorithms, fixed-parameter tractable (FPT) algorithms, exponential time algorithms, and data structures. We propose new directions from the {\em structural perspectives} that connect the aforementioned algorithmic problems to basic questions in combinatorics.
Our approaches fall into one of the three broad schemes: (i) new structural theory, (ii) intermediate problems, and (iii) transfer of techniques. These directions partially build on the PI's successes in resolving more than ten classical problems in this context.
Resolving the proposed problems will likely revolutionize our understanding about algorithms and data structures and potentially unify techniques in multiple algorithmic regimes. Any progress is, in fact, already a significant contribution to the algorithms community. We suggest concrete intermediate goals that are of independent interest and have lower risks, so they are suitable for Ph.D students.
Summary
Real-world optimization problems pose major challenges to algorithmic research. For instance, (i) many important problems are believed to be intractable (i.e. NP-hard) and (ii) with the growth of data size, modern applications often require a decision making under {\em incomplete and dynamically changing input data}. After several decades of research, central problems in these domains have remained poorly understood (e.g. Is there an asymptotically most efficient binary search trees?) Existing algorithmic techniques either reach their limitation or are inherently tailored to special cases.
This project attempts to untangle this gap in the state of the art and seeks new interplay across multiple areas of algorithms, such as approximation algorithms, online algorithms, fixed-parameter tractable (FPT) algorithms, exponential time algorithms, and data structures. We propose new directions from the {\em structural perspectives} that connect the aforementioned algorithmic problems to basic questions in combinatorics.
Our approaches fall into one of the three broad schemes: (i) new structural theory, (ii) intermediate problems, and (iii) transfer of techniques. These directions partially build on the PI's successes in resolving more than ten classical problems in this context.
Resolving the proposed problems will likely revolutionize our understanding about algorithms and data structures and potentially unify techniques in multiple algorithmic regimes. Any progress is, in fact, already a significant contribution to the algorithms community. We suggest concrete intermediate goals that are of independent interest and have lower risks, so they are suitable for Ph.D students.
Max ERC Funding
1 411 258 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym AltCheM
Project In vivo functional screens to decipher mechanisms of stochastically- and mutationally-induced chemoresistance in Acute Myeloid Leukemia
Researcher (PI) Alexandre PUISSANT
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Country France
Call Details Starting Grant (StG), LS4, ERC-2017-STG
Summary Acute Myeloid Leukemia (AML), the most common leukemia diagnosed in adults, represents the paradigm of resistance to front-line therapies in hematology. Indeed, AML is so genetically complex that only few targeted therapies are currently tested in this disease and chemotherapy remains the only standard treatment for AML since the past four decades. Despite an initial sustained remission achieved by chemotherapeutic agents, almost all patients relapse with a chemoresistant minimal residual disease (MRD). The goal of my proposal is to characterize the still poorly understood biological mechanisms underlying persistence and emergence of MRD.
MRD is the consequence of the re-expansion of leukemia-initiating cells that are intrinsically more resistant to chemotherapy. This cell fraction may be stochastically more prone to survive front-line therapy regardless of their mutational status (the stochastic model), or genetically predetermined to resist by virtue of a collection of chemoprotective mutations (the mutational model).
I have already generated in mice, by consecutive rounds of chemotherapy, a stochastic MLL-AF9-driven chemoresistance model that I examined by RNA-sequencing. I will pursue the comprehensive cell autonomous and cell non-autonomous characterization of this chemoresistant AML disease using whole-exome and ChIP-sequencing.
To establish a mutationally-induced chemoresistant mouse model, I will conduct an innovative in vivo screen using pooled mutant open reading frame and shRNA libraries in order to predict which combinations of mutations, among those already known in AML, actively promote chemoresistance.
Finally, by combining genomic profiling and in vivo shRNA screening experiments, I will decipher the molecular mechanisms and identify the functional effectors of these two modes of resistance. Ultimately, I will then be able to firmly establish the fundamental relevance of the stochastic and/or the mutational model of chemoresistance for MRD genesis.
Summary
Acute Myeloid Leukemia (AML), the most common leukemia diagnosed in adults, represents the paradigm of resistance to front-line therapies in hematology. Indeed, AML is so genetically complex that only few targeted therapies are currently tested in this disease and chemotherapy remains the only standard treatment for AML since the past four decades. Despite an initial sustained remission achieved by chemotherapeutic agents, almost all patients relapse with a chemoresistant minimal residual disease (MRD). The goal of my proposal is to characterize the still poorly understood biological mechanisms underlying persistence and emergence of MRD.
MRD is the consequence of the re-expansion of leukemia-initiating cells that are intrinsically more resistant to chemotherapy. This cell fraction may be stochastically more prone to survive front-line therapy regardless of their mutational status (the stochastic model), or genetically predetermined to resist by virtue of a collection of chemoprotective mutations (the mutational model).
I have already generated in mice, by consecutive rounds of chemotherapy, a stochastic MLL-AF9-driven chemoresistance model that I examined by RNA-sequencing. I will pursue the comprehensive cell autonomous and cell non-autonomous characterization of this chemoresistant AML disease using whole-exome and ChIP-sequencing.
To establish a mutationally-induced chemoresistant mouse model, I will conduct an innovative in vivo screen using pooled mutant open reading frame and shRNA libraries in order to predict which combinations of mutations, among those already known in AML, actively promote chemoresistance.
Finally, by combining genomic profiling and in vivo shRNA screening experiments, I will decipher the molecular mechanisms and identify the functional effectors of these two modes of resistance. Ultimately, I will then be able to firmly establish the fundamental relevance of the stochastic and/or the mutational model of chemoresistance for MRD genesis.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym AMPLITUDES
Project Manifesting the Simplicity of Scattering Amplitudes
Researcher (PI) Jacob BOURJAILY
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), PE2, ERC-2017-STG
Summary I propose a program of research that may forever change the way that we understand and use quantum field theory to make predictions for experiment. This will be achieved through the advancement of new, constructive frameworks to determine and represent scattering amplitudes in perturbation theory in terms that depend only on observable quantities, make manifest (all) the symmetries of the theory, and which can be efficiently evaluated while minimally spoiling the underlying simplicity of predictions. My research has already led to the discovery and development of several approaches of this kind.
This proposal describes the specific steps required to extend these ideas to more general theories and to higher orders of perturbation theory. Specifically, the plan of research I propose consists of three concrete goals: to fully characterize the discontinuities of loop amplitudes (`on-shell functions') for a broad class of theories; to develop powerful new representations of loop amplitude {\it integrands}, making manifest as much simplicity as possible; and to develop new techniques for loop amplitude {integration} that are compatible with and preserve the symmetries of observable quantities.
Progress toward any one of these objectives would have important theoretical implications and valuable practical applications. In combination, this proposal has the potential to significantly advance the state of the art for both our theoretical understanding and our computational reach for making predictions for experiment.
To achieve these goals, I will pursue a data-driven, `phenomenological' approach—involving the construction of new computational tools, developed in pursuit of concrete computational targets. For this work, my suitability and expertise is amply demonstrated by my research. I have not only played a key role in many of the most important theoretical developments in the past decade, but I have personally built the most powerful computational tools for their
Summary
I propose a program of research that may forever change the way that we understand and use quantum field theory to make predictions for experiment. This will be achieved through the advancement of new, constructive frameworks to determine and represent scattering amplitudes in perturbation theory in terms that depend only on observable quantities, make manifest (all) the symmetries of the theory, and which can be efficiently evaluated while minimally spoiling the underlying simplicity of predictions. My research has already led to the discovery and development of several approaches of this kind.
This proposal describes the specific steps required to extend these ideas to more general theories and to higher orders of perturbation theory. Specifically, the plan of research I propose consists of three concrete goals: to fully characterize the discontinuities of loop amplitudes (`on-shell functions') for a broad class of theories; to develop powerful new representations of loop amplitude {\it integrands}, making manifest as much simplicity as possible; and to develop new techniques for loop amplitude {integration} that are compatible with and preserve the symmetries of observable quantities.
Progress toward any one of these objectives would have important theoretical implications and valuable practical applications. In combination, this proposal has the potential to significantly advance the state of the art for both our theoretical understanding and our computational reach for making predictions for experiment.
To achieve these goals, I will pursue a data-driven, `phenomenological' approach—involving the construction of new computational tools, developed in pursuit of concrete computational targets. For this work, my suitability and expertise is amply demonstrated by my research. I have not only played a key role in many of the most important theoretical developments in the past decade, but I have personally built the most powerful computational tools for their
Max ERC Funding
1 499 695 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym ARMOR-T
Project Armoring multifunctional T cells for cancer therapy
Researcher (PI) Sebastian Kobold
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Country Germany
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Adoptive T cell therapy (ACT) is a powerful approach to treat even advanced cancer diseases where poor prognosis calls for innovative treatments. However ACT is critically limited by insufficient T cell infiltration into the tumor, T cell activation at the tumor site and local T cell suppression. Few advances have been made in the field to tackle these limitations besides increasing T cell activation. My group has focussed on these unaddressed issues but came to realise that tackling these one by one will not be sufficient. I have developed a panel of unpublished chemokine receptors and innovative modular antibody-activated receptors which have the potential to overcome the limitations of ACT against solid tumors. This ground-breaking portfolio places my group in the unique position to address combination of synergistic receptors and enable cellular therapies in previously unsuccessful indications. My project will provide the rationale for provision of an effective cancer treatment. The goal is to develop the next generation of ACT through T cell engineering both by forced expression of migratory and activating receptors and simultaneous deletion of immune suppressive molecules by gene editing. ARMOR-T will provide the basis for further preclinical and clinical development of a pioneering cellular product devoid of the limitations of available products to date. I will prove 1) synergy between migratory and modular activating receptors, 2) feasibility to integrate gene editing into a T cell expansion protocol, 3) synergy between gene editing, migratory and modular receptors and 4) efficacy, safety and mode of action. The main work of the project will be carried out in models of pancreatic cancer. The ARMOR-T platform will subsequently be translated to other cancer entities where response to ACT is likely such as melanoma, breast or colon cancer, providing less toxic and more effective therapies to otherwise untreatable disease.
Summary
Adoptive T cell therapy (ACT) is a powerful approach to treat even advanced cancer diseases where poor prognosis calls for innovative treatments. However ACT is critically limited by insufficient T cell infiltration into the tumor, T cell activation at the tumor site and local T cell suppression. Few advances have been made in the field to tackle these limitations besides increasing T cell activation. My group has focussed on these unaddressed issues but came to realise that tackling these one by one will not be sufficient. I have developed a panel of unpublished chemokine receptors and innovative modular antibody-activated receptors which have the potential to overcome the limitations of ACT against solid tumors. This ground-breaking portfolio places my group in the unique position to address combination of synergistic receptors and enable cellular therapies in previously unsuccessful indications. My project will provide the rationale for provision of an effective cancer treatment. The goal is to develop the next generation of ACT through T cell engineering both by forced expression of migratory and activating receptors and simultaneous deletion of immune suppressive molecules by gene editing. ARMOR-T will provide the basis for further preclinical and clinical development of a pioneering cellular product devoid of the limitations of available products to date. I will prove 1) synergy between migratory and modular activating receptors, 2) feasibility to integrate gene editing into a T cell expansion protocol, 3) synergy between gene editing, migratory and modular receptors and 4) efficacy, safety and mode of action. The main work of the project will be carried out in models of pancreatic cancer. The ARMOR-T platform will subsequently be translated to other cancer entities where response to ACT is likely such as melanoma, breast or colon cancer, providing less toxic and more effective therapies to otherwise untreatable disease.
Max ERC Funding
1 636 710 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym ARTIST
Project Artificial cell-cell interactions for light switchable cell organization and signaling
Researcher (PI) Seraphine Valeska Wegner
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2017-STG
Summary The bottom-up assembly of tissue from cellular building blocks constitutes a promising, yet highly challenging approach to engineer complex tissues. The challenge lies in controlling cell-cell interactions, which determine how cells organize with respect to each other, how they work together and consequently whether such a multicellular architecture will be functional. The limited spatial and temporal control over cell-cell interactions current biological and chemical approaches provide severely restricts bottom-up tissue engineering. Here, I propose a new way to control cell-cell interactions. I aim to regulate cell-cell interactions with visible light using proteins that reversibly homo- or heterodimerize under blue or red light. These photoswitchable cell-cell interactions provide sustainable, non-invasive, dynamic and reversible control over cell-cell interactions with unprecedented spatial and temporal resolution. First of all, we will focus on various light dependent protein interactions to mediate cell-cell contacts. The detailed characterization (strength, dynamics, interaction modes and orthogonality) of these new photoswitchable cell-cell interactions will provide the framework for the bottom-up construction of tissue-like structures. Secondly, we will use these photoswitchable cell-cell interactions to assemble cells into multicellular architectures with predictable and programmable organization. The dynamic and reversible nature of the photoswitchable contacts will allow us to locally alter interactions at any point in time, to rearrange and obtain asymmetric multicellular structures, which are typical of tissues. Finally, we will also explore how the photoswitchable cell-cell interactions alter cell behavior and signaling. Ultimately, this will pave the way for the bottom-up assembly of multicellular architectures, enabling us to control precisely and dynamically their organization in space and time as well as regulate how cells work together.
Summary
The bottom-up assembly of tissue from cellular building blocks constitutes a promising, yet highly challenging approach to engineer complex tissues. The challenge lies in controlling cell-cell interactions, which determine how cells organize with respect to each other, how they work together and consequently whether such a multicellular architecture will be functional. The limited spatial and temporal control over cell-cell interactions current biological and chemical approaches provide severely restricts bottom-up tissue engineering. Here, I propose a new way to control cell-cell interactions. I aim to regulate cell-cell interactions with visible light using proteins that reversibly homo- or heterodimerize under blue or red light. These photoswitchable cell-cell interactions provide sustainable, non-invasive, dynamic and reversible control over cell-cell interactions with unprecedented spatial and temporal resolution. First of all, we will focus on various light dependent protein interactions to mediate cell-cell contacts. The detailed characterization (strength, dynamics, interaction modes and orthogonality) of these new photoswitchable cell-cell interactions will provide the framework for the bottom-up construction of tissue-like structures. Secondly, we will use these photoswitchable cell-cell interactions to assemble cells into multicellular architectures with predictable and programmable organization. The dynamic and reversible nature of the photoswitchable contacts will allow us to locally alter interactions at any point in time, to rearrange and obtain asymmetric multicellular structures, which are typical of tissues. Finally, we will also explore how the photoswitchable cell-cell interactions alter cell behavior and signaling. Ultimately, this will pave the way for the bottom-up assembly of multicellular architectures, enabling us to control precisely and dynamically their organization in space and time as well as regulate how cells work together.
Max ERC Funding
1 937 000 €
Duration
Start date: 2018-07-01, End date: 2024-06-30
