Project acronym ANTSolve
Project A multi-scale perspective into collective problem solving in ants
Researcher (PI) Ofer Feinerman
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Consolidator Grant (CoG), LS8, ERC-2017-COG
Summary Cognition improves an animal’s ability to tune its responses to environmental conditions. In group living animals, communication works to form a collective cognition that expands the group’s abilities beyond those of individuals. Despite much research, to date, there is little understanding of how collective cognition emerges within biological ensembles. A major obstacle towards such an understanding is the rarity of comprehensive multi-scale empirical data of these complex systems.
We have demonstrated cooperative load transport by ants to be an ideal system to study the emergence of cognition. Similar to other complex cognitive systems, the ants employ high levels of emergence to achieve efficient problem solving over a large range of scenarios. Unique to this system, is its extreme amenability to experimental measurement and manipulation where internal conflicts map to forces, abstract decision making is reflected in direction changes, and future planning manifested in pheromone trails. This allows for an unprecedentedly detailed, multi-scale empirical description of the moment-to-moment unfolding of sophisticated cognitive processes.
This proposal is aimed at materializing this potential to the full. We will examine the ants’ problem solving capabilities under a variety of environmental challenges. We will expose the underpinning rules on the different organizational scales, the flow of information between them, and their relative contributions to collective performance. This will allow for empirical comparisons between the ‘group’ and the ‘sum of its parts’ from which we will quantify the level of emergence in this system. Using the language of information, we will map the boundaries of this group’s collective cognition and relate them to the range of habitable environmental niches. Moreover, we will generalize these insights to formulate a new paradigm of emergence in biological groups opening new horizons in the study of cognitive processes in general.
Summary
Cognition improves an animal’s ability to tune its responses to environmental conditions. In group living animals, communication works to form a collective cognition that expands the group’s abilities beyond those of individuals. Despite much research, to date, there is little understanding of how collective cognition emerges within biological ensembles. A major obstacle towards such an understanding is the rarity of comprehensive multi-scale empirical data of these complex systems.
We have demonstrated cooperative load transport by ants to be an ideal system to study the emergence of cognition. Similar to other complex cognitive systems, the ants employ high levels of emergence to achieve efficient problem solving over a large range of scenarios. Unique to this system, is its extreme amenability to experimental measurement and manipulation where internal conflicts map to forces, abstract decision making is reflected in direction changes, and future planning manifested in pheromone trails. This allows for an unprecedentedly detailed, multi-scale empirical description of the moment-to-moment unfolding of sophisticated cognitive processes.
This proposal is aimed at materializing this potential to the full. We will examine the ants’ problem solving capabilities under a variety of environmental challenges. We will expose the underpinning rules on the different organizational scales, the flow of information between them, and their relative contributions to collective performance. This will allow for empirical comparisons between the ‘group’ and the ‘sum of its parts’ from which we will quantify the level of emergence in this system. Using the language of information, we will map the boundaries of this group’s collective cognition and relate them to the range of habitable environmental niches. Moreover, we will generalize these insights to formulate a new paradigm of emergence in biological groups opening new horizons in the study of cognitive processes in general.
Max ERC Funding
2 000 000 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym BioMet
Project Selective Functionalization of Saturated Hydrocarbons
Researcher (PI) Ilan MAREK
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Advanced Grant (AdG), PE5, ERC-2017-ADG
Summary Despite that C–H functionalization represents a paradigm shift from the standard logic of organic synthesis, the selective activation of non-functionalized alkanes has puzzled chemists for centuries and is always referred to one of the remaining major challenges in chemical sciences. Alkanes are inert compounds representing the major constituents of natural gas and petroleum. Converting these cheap and widely available hydrocarbon feedstocks into added-value intermediates would tremendously affect the field of chemistry. For long saturated hydrocarbons, one must distinguish between non-equivalent but chemically very similar alkane substrate C−H bonds, and for functionalization at the terminus position, one must favor activation of the stronger, primary C−H bonds at the expense of weaker and numerous secondary C-H bonds. The goal of this work is to develop a general principle in organic synthesis for the preparation of a wide variety of more complex molecular architectures from saturated hydrocarbons. In our approach, the alkane will first be transformed into an alkene that will subsequently be engaged in a metal-catalyzed hydrometalation/migration sequence. The first step of the sequence, ideally represented by the removal of two hydrogen atoms, will be performed by the use of a mutated strain of Rhodococcus. The position and geometry of the formed double bond has no effect on the second step of the reaction as the metal-catalyzed hydrometalation/migration will isomerize the double bond along the carbon skeleton to selectively produce the primary organometallic species. Trapping the resulting organometallic derivatives with a large variety of electrophiles will provide the desired functionalized alkane. This work will lead to the invention of new, selective and efficient processes for the utilization of simple hydrocarbons and valorize the synthetic potential of raw hydrocarbon feedstock for the environmentally benign production of new compounds and new materials.
Summary
Despite that C–H functionalization represents a paradigm shift from the standard logic of organic synthesis, the selective activation of non-functionalized alkanes has puzzled chemists for centuries and is always referred to one of the remaining major challenges in chemical sciences. Alkanes are inert compounds representing the major constituents of natural gas and petroleum. Converting these cheap and widely available hydrocarbon feedstocks into added-value intermediates would tremendously affect the field of chemistry. For long saturated hydrocarbons, one must distinguish between non-equivalent but chemically very similar alkane substrate C−H bonds, and for functionalization at the terminus position, one must favor activation of the stronger, primary C−H bonds at the expense of weaker and numerous secondary C-H bonds. The goal of this work is to develop a general principle in organic synthesis for the preparation of a wide variety of more complex molecular architectures from saturated hydrocarbons. In our approach, the alkane will first be transformed into an alkene that will subsequently be engaged in a metal-catalyzed hydrometalation/migration sequence. The first step of the sequence, ideally represented by the removal of two hydrogen atoms, will be performed by the use of a mutated strain of Rhodococcus. The position and geometry of the formed double bond has no effect on the second step of the reaction as the metal-catalyzed hydrometalation/migration will isomerize the double bond along the carbon skeleton to selectively produce the primary organometallic species. Trapping the resulting organometallic derivatives with a large variety of electrophiles will provide the desired functionalized alkane. This work will lead to the invention of new, selective and efficient processes for the utilization of simple hydrocarbons and valorize the synthetic potential of raw hydrocarbon feedstock for the environmentally benign production of new compounds and new materials.
Max ERC Funding
2 499 375 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym Ca2Coral
Project Elucidating the molecular and biophysical mechanism of coral calcification in view of the future acidified ocean
Researcher (PI) Tali Mass
Host Institution (HI) UNIVERSITY OF HAIFA
Call Details Starting Grant (StG), LS8, ERC-2017-STG
Summary Although various aspects of biomineralisation in corals have been studied for decades, the basic mechanism of precipitation of the aragonite skeleton remains enigmatic. Two parallel lines of inquiry have emerged: geochemist models of calcification that are directly related to seawater carbonate chemistry at thermodynamic equilibrium. Here, the role of the organisms in the precipitation reaction is largely ignored. The second line is based on biological considerations of the biomineralisation process, which focuses on models of biophysical processes far from thermodynamic equilibrium that concentrate calcium ions, anions and proteins responsible for nucleation in specific compartments. Recently, I identified and cloned a group of highly acidic proteins derived the common stony coral, Stylophora pistillata. All of the cloned proteins precipitate aragonite in seawater at pH 8.2 and 7.6 in-vitro. However, it is not at all clear if the expression of these proteins in-vivo is sufficient for the formation of an aragonite skeleton at seawater pH values below ~7.8. Here using a combination of molecular, biophysical, genomic, and cell biological approaches, we proposed to test the core hypothesis that, unless wounded or otherwise having skeletal material exposed directly to seawater, stony zooxanthellate corals will continue to calcify at pH values projected for the CO2 emissions scenarios for 2100.
Specifically, the objectives of Ca2Coral are to:
1) Use functional genomics to identify the key genes and proteins involved both in the organic matrix and skeleton formation in the adult holobiont and during its larval development.
2) Use a genetics approach to elucidate the roles of specific proteins in the biomineralisation process.
3) Use ultra-high resolution imaging and spectroscopic analysis at different pH levels to elucidate the biomineralisation pathways and mineral precursor in corals in the adult holobiont and during its larval development.
Summary
Although various aspects of biomineralisation in corals have been studied for decades, the basic mechanism of precipitation of the aragonite skeleton remains enigmatic. Two parallel lines of inquiry have emerged: geochemist models of calcification that are directly related to seawater carbonate chemistry at thermodynamic equilibrium. Here, the role of the organisms in the precipitation reaction is largely ignored. The second line is based on biological considerations of the biomineralisation process, which focuses on models of biophysical processes far from thermodynamic equilibrium that concentrate calcium ions, anions and proteins responsible for nucleation in specific compartments. Recently, I identified and cloned a group of highly acidic proteins derived the common stony coral, Stylophora pistillata. All of the cloned proteins precipitate aragonite in seawater at pH 8.2 and 7.6 in-vitro. However, it is not at all clear if the expression of these proteins in-vivo is sufficient for the formation of an aragonite skeleton at seawater pH values below ~7.8. Here using a combination of molecular, biophysical, genomic, and cell biological approaches, we proposed to test the core hypothesis that, unless wounded or otherwise having skeletal material exposed directly to seawater, stony zooxanthellate corals will continue to calcify at pH values projected for the CO2 emissions scenarios for 2100.
Specifically, the objectives of Ca2Coral are to:
1) Use functional genomics to identify the key genes and proteins involved both in the organic matrix and skeleton formation in the adult holobiont and during its larval development.
2) Use a genetics approach to elucidate the roles of specific proteins in the biomineralisation process.
3) Use ultra-high resolution imaging and spectroscopic analysis at different pH levels to elucidate the biomineralisation pathways and mineral precursor in corals in the adult holobiont and during its larval development.
Max ERC Funding
1 499 741 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym CRISPR-EVOL
Project The eco-evolutionary costs and benefits of CRISPR-Cas systems, and their effect on genome diversity within populations
Researcher (PI) Uri Gophna
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Advanced Grant (AdG), LS8, ERC-2017-ADG
Summary CRISPR-Cas systems are microbial defense systems that provide prokaryotes with acquired and heritable DNA-based immunity against selfish genetic elements, primarily viruses. However, the full scope of benefits that these systems can provide, as well as their costs remain unknown. Specifically, it is unclear whether the benefits against viral infection outweigh the continual costs incurred even in the absence of parasitic elements, and whether CRISPR-Cas systems affect microbial genome diversity in nature.
Since CRISPR-Cas systems can impede lateral gene transfer, it is often assumed that they reduce genetic diversity. Conversely, our recent results suggest the exact opposite: that these systems generate a high level of genomic diversity within populations. We have recently combined genomics of environmental strains and experimental genetics to show that archaea frequently acquire CRISPR immune memory, known as spacers, from chromosomes of related species in the environment. The presence of these spacers reduces gene exchange between lineages, indicating that CRISPR-Cas contributes to diversification. We have also shown that such inter-species mating events induce the acquisition of spacers against a strain's own replicons, supporting a role for CRISPR-Cas systems in generating deletions in natural plasmids and unessential genomic loci, again increasing genome diversity within populations.
Here we aim to test our hypothesis that CRISPR-Cas systems increase within-population diversity, and quantify their benefits to both cells and populations, using large-scale genomics and experimental evolution. We will explore how these systems alter the patterns of recombination within and between species, and explore the potential involvement of CRISPR-associated proteins in cellular DNA repair.
This work will reveal the eco-evolutionary role of CRISPR-Cas systems in shaping microbial populations, and open new research avenues regarding additional roles beyond anti-viral defense
Summary
CRISPR-Cas systems are microbial defense systems that provide prokaryotes with acquired and heritable DNA-based immunity against selfish genetic elements, primarily viruses. However, the full scope of benefits that these systems can provide, as well as their costs remain unknown. Specifically, it is unclear whether the benefits against viral infection outweigh the continual costs incurred even in the absence of parasitic elements, and whether CRISPR-Cas systems affect microbial genome diversity in nature.
Since CRISPR-Cas systems can impede lateral gene transfer, it is often assumed that they reduce genetic diversity. Conversely, our recent results suggest the exact opposite: that these systems generate a high level of genomic diversity within populations. We have recently combined genomics of environmental strains and experimental genetics to show that archaea frequently acquire CRISPR immune memory, known as spacers, from chromosomes of related species in the environment. The presence of these spacers reduces gene exchange between lineages, indicating that CRISPR-Cas contributes to diversification. We have also shown that such inter-species mating events induce the acquisition of spacers against a strain's own replicons, supporting a role for CRISPR-Cas systems in generating deletions in natural plasmids and unessential genomic loci, again increasing genome diversity within populations.
Here we aim to test our hypothesis that CRISPR-Cas systems increase within-population diversity, and quantify their benefits to both cells and populations, using large-scale genomics and experimental evolution. We will explore how these systems alter the patterns of recombination within and between species, and explore the potential involvement of CRISPR-associated proteins in cellular DNA repair.
This work will reveal the eco-evolutionary role of CRISPR-Cas systems in shaping microbial populations, and open new research avenues regarding additional roles beyond anti-viral defense
Max ERC Funding
2 495 625 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym LifeLikeMat
Project Dissipative self-assembly in synthetic systems: Towards life-like materials
Researcher (PI) Rafal KLAJN
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Consolidator Grant (CoG), PE5, ERC-2018-COG
Summary "Living organisms are sophisticated self-assembled structures that exist and operate far from thermodynamic equilibrium and, as such, represent the ultimate example of dissipative self-assembly. They remain stable at highly organized (low-entropy) states owing to the continuous consumption of energy stored in ""chemical fuels"", which they convert into low-energy waste. Dissipative self-assembly is ubiquitous in nature, where it gives rise to complex structures and properties such as self-healing, homeostasis, and camouflage. In sharp contrast, nearly all man-made materials are static: they are designed to serve a given purpose rather than to exhibit different properties dependent on external conditions. Developing the means to rationally design dissipative self-assembly constructs will greatly impact a range of industries, including the pharmaceutical and energy sectors.
The goal of the proposed research program is to develop novel principles for designing dissipative self-assembly systems and to fabricate a range of dissipative materials based on these principles. To achieve this goal, we will employ novel, unconventional approaches based predominantly on integrating organic and colloidal-inorganic building blocks.
Specifically, we will (WP1) drive dissipative self-assembly using chemical reactions such as polymerization, oxidation of sugars, and CO2-to-methanol conversion, (WP2) develop new modes of intrinsically dissipative self-assembly, whereby the activated building blocks are inherently unstable, and (WP3&4) conceive systems whereby self-assembly is spontaneously followed by disassembly.
The proposed studies will lead to new classes of ""driven"" materials with features such as tunable lifetimes, time-dependent electrical conductivity, and dynamic exchange of building blocks. Overall, this project will lay the foundations for developing new synthetic dissipative materials, bringing us closer to the rich and varied functionality of materials found in nature."
Summary
"Living organisms are sophisticated self-assembled structures that exist and operate far from thermodynamic equilibrium and, as such, represent the ultimate example of dissipative self-assembly. They remain stable at highly organized (low-entropy) states owing to the continuous consumption of energy stored in ""chemical fuels"", which they convert into low-energy waste. Dissipative self-assembly is ubiquitous in nature, where it gives rise to complex structures and properties such as self-healing, homeostasis, and camouflage. In sharp contrast, nearly all man-made materials are static: they are designed to serve a given purpose rather than to exhibit different properties dependent on external conditions. Developing the means to rationally design dissipative self-assembly constructs will greatly impact a range of industries, including the pharmaceutical and energy sectors.
The goal of the proposed research program is to develop novel principles for designing dissipative self-assembly systems and to fabricate a range of dissipative materials based on these principles. To achieve this goal, we will employ novel, unconventional approaches based predominantly on integrating organic and colloidal-inorganic building blocks.
Specifically, we will (WP1) drive dissipative self-assembly using chemical reactions such as polymerization, oxidation of sugars, and CO2-to-methanol conversion, (WP2) develop new modes of intrinsically dissipative self-assembly, whereby the activated building blocks are inherently unstable, and (WP3&4) conceive systems whereby self-assembly is spontaneously followed by disassembly.
The proposed studies will lead to new classes of ""driven"" materials with features such as tunable lifetimes, time-dependent electrical conductivity, and dynamic exchange of building blocks. Overall, this project will lay the foundations for developing new synthetic dissipative materials, bringing us closer to the rich and varied functionality of materials found in nature."
Max ERC Funding
1 999 572 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym SynProAtCell
Project Delivery and On-Demand Activation of Chemically Synthesized and Uniquely Modified Proteins in Living Cells
Researcher (PI) Ashraf BRIK
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Advanced Grant (AdG), PE5, ERC-2018-ADG
Summary While advanced molecular biology approaches provide insight on the role of proteins in cellular processes, their ability to freely modify proteins and control their functions when desired is limited, hindering the achievement of a detailed understanding of the cellular functions of numerous proteins. At the same time, chemical synthesis of proteins allows for unlimited protein design, enabling the preparation of unique protein analogues that are otherwise difficult or impossible to obtain. However, effective methods to introduce these designed proteins into cells are for the most part limited to simple systems. To monitor proteins cellular functions and fates in real time, and in order to answer currently unanswerable fundamental questions about the cellular roles of proteins, the fields of protein synthesis and cellular protein manipulation must be bridged by significant advances in methods for protein delivery and real-time activation. Here, we propose to develop a general approach for enabling considerably more detailed in-cell study of uniquely modified proteins by preparing proteins having the following features: 1) traceless cell delivery unit(s), 2) an activation unit for on-demand activation of protein function in the cell, and 3) a fluorescence probe for monitoring the state and the fate of the protein.
We will adopt this approach to shed light on the processes of ubiquitination and deubiquitination, which are critical cellular signals for many biological processes. We will employ our approach to study 1) the effect of inhibition of deubiquitinases in cancer. 2) Examining effect of phosphorylation on proteasomal degradation and on ubiquitin chain elongation. 3) Examining effect of covalent attachment of a known ligase ligand to a target protein on its degradation Moreover, which could trigger the development of new methods to modify the desired protein in cell by selective chemistries and so rationally promote their degradation.
Summary
While advanced molecular biology approaches provide insight on the role of proteins in cellular processes, their ability to freely modify proteins and control their functions when desired is limited, hindering the achievement of a detailed understanding of the cellular functions of numerous proteins. At the same time, chemical synthesis of proteins allows for unlimited protein design, enabling the preparation of unique protein analogues that are otherwise difficult or impossible to obtain. However, effective methods to introduce these designed proteins into cells are for the most part limited to simple systems. To monitor proteins cellular functions and fates in real time, and in order to answer currently unanswerable fundamental questions about the cellular roles of proteins, the fields of protein synthesis and cellular protein manipulation must be bridged by significant advances in methods for protein delivery and real-time activation. Here, we propose to develop a general approach for enabling considerably more detailed in-cell study of uniquely modified proteins by preparing proteins having the following features: 1) traceless cell delivery unit(s), 2) an activation unit for on-demand activation of protein function in the cell, and 3) a fluorescence probe for monitoring the state and the fate of the protein.
We will adopt this approach to shed light on the processes of ubiquitination and deubiquitination, which are critical cellular signals for many biological processes. We will employ our approach to study 1) the effect of inhibition of deubiquitinases in cancer. 2) Examining effect of phosphorylation on proteasomal degradation and on ubiquitin chain elongation. 3) Examining effect of covalent attachment of a known ligase ligand to a target protein on its degradation Moreover, which could trigger the development of new methods to modify the desired protein in cell by selective chemistries and so rationally promote their degradation.
Max ERC Funding
2 500 000 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym TheSocialBusiness
Project The advantages and pitfalls of elicitated online user engagement
Researcher (PI) Gal Oestreicher-Singer
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), SH1, ERC-2017-STG
Summary The notion that websites benefit when their users are socially engaged—i.e., when they interact with content and with other users—has become so entrenched it is practically an axiom. Accordingly, websites in numerous domains invest heavily in ‘social computing’ features that encourage such engagement. In fact, many attempt to elicit engagement proactively, through the use of calls to action—prompts that ask users to carry out participatory actions such as rating or ‘liking’ content. Given the vast popularity of social computing, it is surprising how little we actually know about how user engagement affects websites and their users. From a business perspective, the direct value of user engagement is far from clear. From a societal perspective, it is unclear whether the increasing expectation for users to engage with firms may lead users to behave in ways that do not serve them. This research aims to provide a comprehensive understanding of user engagement, and specifically, engagement elicited by calls to action, from those two perspectives. I will use an empirical approach, relying on innovative lab and large-scale field experiments. The lab experiments leverage a specially-designed website. For the field experiments, we will collaborate with websites spanning several domains; we have already initiated a relationship with a leading website-development service provider that uses a freemium business model, and have been able to observe the actual behavior of its users. Our preliminary results are promising, supporting the idea that calls to action have strong effects on conversion and information revelation. Moving forward, I plan to fully characterize the nature of these effects in multiple product domains, and to isolate their underlying mechanisms. I am confident that this research program will transform our understanding of the economic and broader societal impact of the social computing phenomenon.
Summary
The notion that websites benefit when their users are socially engaged—i.e., when they interact with content and with other users—has become so entrenched it is practically an axiom. Accordingly, websites in numerous domains invest heavily in ‘social computing’ features that encourage such engagement. In fact, many attempt to elicit engagement proactively, through the use of calls to action—prompts that ask users to carry out participatory actions such as rating or ‘liking’ content. Given the vast popularity of social computing, it is surprising how little we actually know about how user engagement affects websites and their users. From a business perspective, the direct value of user engagement is far from clear. From a societal perspective, it is unclear whether the increasing expectation for users to engage with firms may lead users to behave in ways that do not serve them. This research aims to provide a comprehensive understanding of user engagement, and specifically, engagement elicited by calls to action, from those two perspectives. I will use an empirical approach, relying on innovative lab and large-scale field experiments. The lab experiments leverage a specially-designed website. For the field experiments, we will collaborate with websites spanning several domains; we have already initiated a relationship with a leading website-development service provider that uses a freemium business model, and have been able to observe the actual behavior of its users. Our preliminary results are promising, supporting the idea that calls to action have strong effects on conversion and information revelation. Moving forward, I plan to fully characterize the nature of these effects in multiple product domains, and to isolate their underlying mechanisms. I am confident that this research program will transform our understanding of the economic and broader societal impact of the social computing phenomenon.
Max ERC Funding
1 487 500 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
