Project acronym Amitochondriates
Project Life without mitochondrion
Researcher (PI) Vladimir HAMPL
Host Institution (HI) UNIVERZITA KARLOVA
Country Czechia
Call Details Consolidator Grant (CoG), LS8, ERC-2017-COG
Summary Mitochondria are often referred to as the “power houses” of eukaryotic cells. All eukaryotes were thought to have mitochondria of some form until 2016, when the first eukaryote thriving without mitochondria was discovered by our laboratory – a flagellate Monocercomonoides. Understanding cellular functions of these cells, which represent a new functional type of eukaryotes, and understanding the circumstances of the unique event of mitochondrial loss are motivations for this proposal. The first objective focuses on the cell physiology. We will perform a metabolomic study revealing major metabolic pathways and concentrate further on elucidating its unique system of iron-sulphur cluster assembly. In the second objective, we will investigate in details the unique case of mitochondrial loss. We will examine two additional potentially amitochondriate lineages by means of genomics and transcriptomics, conduct experiments simulating the moments of mitochondrial loss and try to induce the mitochondrial loss in vitro by knocking out or down genes for mitochondrial biogenesis. We have chosen Giardia intestinalis and Entamoeba histolytica as models for the latter experiments, because their mitochondria are already reduced to minimalistic “mitosomes” and because some genetic tools are already available for them. Successful mitochondrial knock-outs would enable us to study mitochondrial loss in ‘real time’ and in vivo. In the third objective, we will focus on transforming Monocercomonoides into a tractable laboratory model by developing methods of axenic cultivation and genetic manipulation. This will open new possibilities in the studies of this organism and create a cell culture representing an amitochondriate model for cell biological studies enabling the dissection of mitochondrial effects from those of other compartments. The team is composed of the laboratory of PI and eight invited experts and we hope it has the ability to address these challenging questions.
Summary
Mitochondria are often referred to as the “power houses” of eukaryotic cells. All eukaryotes were thought to have mitochondria of some form until 2016, when the first eukaryote thriving without mitochondria was discovered by our laboratory – a flagellate Monocercomonoides. Understanding cellular functions of these cells, which represent a new functional type of eukaryotes, and understanding the circumstances of the unique event of mitochondrial loss are motivations for this proposal. The first objective focuses on the cell physiology. We will perform a metabolomic study revealing major metabolic pathways and concentrate further on elucidating its unique system of iron-sulphur cluster assembly. In the second objective, we will investigate in details the unique case of mitochondrial loss. We will examine two additional potentially amitochondriate lineages by means of genomics and transcriptomics, conduct experiments simulating the moments of mitochondrial loss and try to induce the mitochondrial loss in vitro by knocking out or down genes for mitochondrial biogenesis. We have chosen Giardia intestinalis and Entamoeba histolytica as models for the latter experiments, because their mitochondria are already reduced to minimalistic “mitosomes” and because some genetic tools are already available for them. Successful mitochondrial knock-outs would enable us to study mitochondrial loss in ‘real time’ and in vivo. In the third objective, we will focus on transforming Monocercomonoides into a tractable laboratory model by developing methods of axenic cultivation and genetic manipulation. This will open new possibilities in the studies of this organism and create a cell culture representing an amitochondriate model for cell biological studies enabling the dissection of mitochondrial effects from those of other compartments. The team is composed of the laboratory of PI and eight invited experts and we hope it has the ability to address these challenging questions.
Max ERC Funding
1 935 500 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym BEHAVFRICTIONS
Project Behavioral Implications of Information-Processing Frictions
Researcher (PI) Jakub STEINER
Host Institution (HI) NARODOHOSPODARSKY USTAV AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE
Country Czechia
Call Details Consolidator Grant (CoG), SH1, ERC-2017-COG
Summary BEHAVFRICTIONS will use novel models focussing on information-processing frictions to explain choice patterns described in behavioral economics and psychology. The proposed research will provide microfoundations that are essential for (i) identification of stable preferences, (ii) counterfactual predictions, and (iii) normative conclusions.
(i) Agents who face information-processing costs must trade the precision of choice against information costs. Their behavior thus reflects both their stable preferences and the context-dependent procedures that manage their errors stemming from imperfect information processing. In the absence of micro-founded models, the two drivers of the behavior are difficult to disentangle for outside observers. In some pillars of the proposal, the agents follow choice rules that closely resemble logit rules used in structural estimation. This will allow me to reinterpret the structural estimation fits to choice data and to make a distinction between the stable preferences and frictions.
(ii) Such a distinction is important in counterfactual policy analysis because the second-best decision procedures that manage the errors in choice are affected by the analysed policy. Incorporation of the information-processing frictions into existing empirical methods will improve our ability to predict effects of the policies.
(iii) My preliminary results suggest that when an agent is prone to committing errors, biases--such as overconfidence, confirmatory bias, or perception biases known from prospect theory--arise under second-best strategies. By providing the link between the agent's environment and the second-best distribution of the perception errors, my models will delineate environments in which these biases shield the agents from the most costly mistakes from environments in which the biases turn into maladaptations. The distinction will inform the normative debate on debiasing.
Summary
BEHAVFRICTIONS will use novel models focussing on information-processing frictions to explain choice patterns described in behavioral economics and psychology. The proposed research will provide microfoundations that are essential for (i) identification of stable preferences, (ii) counterfactual predictions, and (iii) normative conclusions.
(i) Agents who face information-processing costs must trade the precision of choice against information costs. Their behavior thus reflects both their stable preferences and the context-dependent procedures that manage their errors stemming from imperfect information processing. In the absence of micro-founded models, the two drivers of the behavior are difficult to disentangle for outside observers. In some pillars of the proposal, the agents follow choice rules that closely resemble logit rules used in structural estimation. This will allow me to reinterpret the structural estimation fits to choice data and to make a distinction between the stable preferences and frictions.
(ii) Such a distinction is important in counterfactual policy analysis because the second-best decision procedures that manage the errors in choice are affected by the analysed policy. Incorporation of the information-processing frictions into existing empirical methods will improve our ability to predict effects of the policies.
(iii) My preliminary results suggest that when an agent is prone to committing errors, biases--such as overconfidence, confirmatory bias, or perception biases known from prospect theory--arise under second-best strategies. By providing the link between the agent's environment and the second-best distribution of the perception errors, my models will delineate environments in which these biases shield the agents from the most costly mistakes from environments in which the biases turn into maladaptations. The distinction will inform the normative debate on debiasing.
Max ERC Funding
1 321 488 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym POLICYAID
Project Policy, practice and patient experience in the age of intensified data sourcing
Researcher (PI) Klaus Lindgaard Hoeyer
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Consolidator Grant (CoG), SH2, ERC-2015-CoG
Summary The European healthcare services have begun collecting tissue samples and healthcare data from patients on an unprecedented scale. With POLICYAID we suggest the term 'intensified data sourcing' to describe these attempts at getting more data, on more people, of better quality while simultaneously making the data available for multiple uses. Data are used for research, for financial remuneration purposes, for quality assurance, to attract capital and even for police work. POLICYAID investigates how the diverse agendas interact in the making of a new infrastructure for healthcare.
POLICYAID ambitiously aims to understand the drivers for and implications of intensified data sourcing in the biomedical realm across three levels: 1) policymaking, 2) everyday clinical practices, and 3) citizen experiences of health, illness, rights and duties. To achieve this aim we compare four different forms of intensified data sourcing, and analyze the regulatory frameworks guiding the data procurement and use in Denmark, the EU and beyond.
Based on PI’s strong inter-disciplinary background and experience, we fuse legal, sociological, anthropological and public health scholarship and develop new methodologies for policy analysis by combining document analysis, interviews, participant observation and register-based methodologies. Instead of simply assuming that data sourcing can be reduced to matters of surveillance, we open up the black box of data sourcing by describing how data are selected; financed; what they are used for; how data practices relate to the involved stakeholders' hopes and concerns, and; who gains which rights to the data. We can thereby explore how intensified data sourcing affects clinical routines and patient experience, as well as understand how Big Data for medical research emerges. POLICYAID thereby arrives at novel understandings of both policy making and what it means to be patient in the age of intensified data sourcing.
Summary
The European healthcare services have begun collecting tissue samples and healthcare data from patients on an unprecedented scale. With POLICYAID we suggest the term 'intensified data sourcing' to describe these attempts at getting more data, on more people, of better quality while simultaneously making the data available for multiple uses. Data are used for research, for financial remuneration purposes, for quality assurance, to attract capital and even for police work. POLICYAID investigates how the diverse agendas interact in the making of a new infrastructure for healthcare.
POLICYAID ambitiously aims to understand the drivers for and implications of intensified data sourcing in the biomedical realm across three levels: 1) policymaking, 2) everyday clinical practices, and 3) citizen experiences of health, illness, rights and duties. To achieve this aim we compare four different forms of intensified data sourcing, and analyze the regulatory frameworks guiding the data procurement and use in Denmark, the EU and beyond.
Based on PI’s strong inter-disciplinary background and experience, we fuse legal, sociological, anthropological and public health scholarship and develop new methodologies for policy analysis by combining document analysis, interviews, participant observation and register-based methodologies. Instead of simply assuming that data sourcing can be reduced to matters of surveillance, we open up the black box of data sourcing by describing how data are selected; financed; what they are used for; how data practices relate to the involved stakeholders' hopes and concerns, and; who gains which rights to the data. We can thereby explore how intensified data sourcing affects clinical routines and patient experience, as well as understand how Big Data for medical research emerges. POLICYAID thereby arrives at novel understandings of both policy making and what it means to be patient in the age of intensified data sourcing.
Max ERC Funding
1 972 860 €
Duration
Start date: 2016-06-01, End date: 2021-11-30
Project acronym RNA ORIGAMI
Project RNA-protein Nanostructures for Synthetic Biology
Researcher (PI) Ebbe Sloth Andersen
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Consolidator Grant (CoG), LS9, ERC-2015-CoG
Summary Synthetic biology aims at re-engineering organisms for practical applications by designing novel biomolecular components, networks, and pathways. The field is expected to lead to cheaper drugs, sustainable fuel production, efficient diagnosis and targeted therapies for diseases. However, a major obstacle to achieve these goals is our limited ability to rationally design biomolecular structure and function. By contrast, the field of DNA nanotechnology has so far demonstrated an unprecedented ability to design and self-assemble well-defined molecular shapes, although the production method of thermal annealing is not compatible with cells. We have recently demonstrated a breakthrough method, called RNA origami, which allows the design of RNA molecules that fold into well-defined nanoscale shapes during their synthesis by an RNA polymerase. In this proposal I aim at extending this technology to produce RNA-protein nanostructures and at demonstrating their application in synthetic biology. My primary scientific hypothesis is that understanding the folding process during synthesis will help us to design nanostructures that can be produced in cells. I will design a general RNA-protein architecture that is compatible with folding during synthesis. I will investigate folding kinetics to be able to design and program the dynamical folding process. Based on this, RNA-protein nanostructures will be designed, expressed in cells, and verified, for the formation of the desired shapes. We will develop new functionalities by both rational design and selection approaches with the aim of obtaining multivalent-binding and switching properties. Finally, the functional RNA-protein nanostructures will be applied in proof-of-concept experiments to demonstrate efficient, multivalent targeting of subcellular structures, biosensing of a variety of intracellular analytes, metabolic channeling of biosynthesis pathways, and complex control of transcriptional networks.
Summary
Synthetic biology aims at re-engineering organisms for practical applications by designing novel biomolecular components, networks, and pathways. The field is expected to lead to cheaper drugs, sustainable fuel production, efficient diagnosis and targeted therapies for diseases. However, a major obstacle to achieve these goals is our limited ability to rationally design biomolecular structure and function. By contrast, the field of DNA nanotechnology has so far demonstrated an unprecedented ability to design and self-assemble well-defined molecular shapes, although the production method of thermal annealing is not compatible with cells. We have recently demonstrated a breakthrough method, called RNA origami, which allows the design of RNA molecules that fold into well-defined nanoscale shapes during their synthesis by an RNA polymerase. In this proposal I aim at extending this technology to produce RNA-protein nanostructures and at demonstrating their application in synthetic biology. My primary scientific hypothesis is that understanding the folding process during synthesis will help us to design nanostructures that can be produced in cells. I will design a general RNA-protein architecture that is compatible with folding during synthesis. I will investigate folding kinetics to be able to design and program the dynamical folding process. Based on this, RNA-protein nanostructures will be designed, expressed in cells, and verified, for the formation of the desired shapes. We will develop new functionalities by both rational design and selection approaches with the aim of obtaining multivalent-binding and switching properties. Finally, the functional RNA-protein nanostructures will be applied in proof-of-concept experiments to demonstrate efficient, multivalent targeting of subcellular structures, biosensing of a variety of intracellular analytes, metabolic channeling of biosynthesis pathways, and complex control of transcriptional networks.
Max ERC Funding
1 999 935 €
Duration
Start date: 2016-04-01, End date: 2021-03-31
