Project acronym 3DWATERWAVES
Project Mathematical aspects of three-dimensional water waves with vorticity
Researcher (PI) Erik Torsten Wahlen
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE1, ERC-2015-STG
Summary The goal of this project is to develop a mathematical theory for steady three-dimensional water waves with vorticity. The mathematical model consists of the incompressible Euler equations with a free surface, and vorticity is important for modelling the interaction of surface waves with non-uniform currents. In the two-dimensional case, there has been a lot of progress on water waves with vorticity in the last decade. This progress has mainly been based on the stream function formulation, in which the problem is reformulated as a nonlinear elliptic free boundary problem. An analogue of this formulation is not available in three dimensions, and the theory has therefore so far been restricted to irrotational flow. In this project we seek to go beyond this restriction using two different approaches. In the first approach we will adapt methods which have been used to construct three-dimensional ideal flows with vorticity in domains with a fixed boundary to the free boundary context (for example Beltrami flows). In the second approach we will develop methods which are new even in the case of a fixed boundary, by performing a detailed study of the structure of the equations close to a given shear flow using ideas from infinite-dimensional bifurcation theory. This involves handling infinitely many resonances.
Summary
The goal of this project is to develop a mathematical theory for steady three-dimensional water waves with vorticity. The mathematical model consists of the incompressible Euler equations with a free surface, and vorticity is important for modelling the interaction of surface waves with non-uniform currents. In the two-dimensional case, there has been a lot of progress on water waves with vorticity in the last decade. This progress has mainly been based on the stream function formulation, in which the problem is reformulated as a nonlinear elliptic free boundary problem. An analogue of this formulation is not available in three dimensions, and the theory has therefore so far been restricted to irrotational flow. In this project we seek to go beyond this restriction using two different approaches. In the first approach we will adapt methods which have been used to construct three-dimensional ideal flows with vorticity in domains with a fixed boundary to the free boundary context (for example Beltrami flows). In the second approach we will develop methods which are new even in the case of a fixed boundary, by performing a detailed study of the structure of the equations close to a given shear flow using ideas from infinite-dimensional bifurcation theory. This involves handling infinitely many resonances.
Max ERC Funding
1 203 627 €
Duration
Start date: 2016-03-01, End date: 2022-02-28
Project acronym 3DX-FLASH
Project Probing MHz processes in 3D with X-ray microscopy
Researcher (PI) Pablo Villanueva Perez
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE4, ERC-2020-STG
Summary I aim to develop an X-ray imaging technique capable of filming processes in 3D, with a temporal resolution several orders of magnitude faster than up-to-date 3D X-ray imaging techniques.
The unique penetration power of X-rays allows us to study systems in their native environment. This property has led to the development of X-ray microtomography (µCT). µCT acquires 3D information, which determines the functionality and mechanical properties of nature, by rotating a sample with respect to the X-ray source. µCT is a crucial tool for several scientific disciplines such as physics, biology, and chemistry.
Over the last decade, µCT has become a technique capable of not only recording 3D information but also filming dynamical processes. Several breakthroughs have made this possible: i) intense X-ray sources (synchrotron light sources), ii) efficient and fast X-ray detectors, and iii) fast 3D reconstruction algorithms. Despite all of these developments, the acquisition protocols remain unchanged, i.e., the sample is only rotated faster. This fast rotation introduces forces which may alter the studied dynamics and ultimately limit the achievable temporal resolution.
My project is to establish an X-ray microscope that avoids the sample rotation, obtaining 3D information from a single X-ray flash by splitting it into nine-angularly resolved beams which illuminate the sample simultaneously. This approach, when implemented at intense X-ray sources such as synchrotron light sources and X-ray free-electron lasers, will allow the filming of natural processes with micrometer to nanometer resolution and resolve dynamics from microseconds to femtoseconds. To demonstrate its capabilities, I will study fundamental processes in cellulose fibers, a renewable biomaterial, which can replace fossil-based materials, such as plastics. This technique will open up the possibility to film dynamics in 3D to answer questions coming from industry and natural sciences at rates not accessible today.
Summary
I aim to develop an X-ray imaging technique capable of filming processes in 3D, with a temporal resolution several orders of magnitude faster than up-to-date 3D X-ray imaging techniques.
The unique penetration power of X-rays allows us to study systems in their native environment. This property has led to the development of X-ray microtomography (µCT). µCT acquires 3D information, which determines the functionality and mechanical properties of nature, by rotating a sample with respect to the X-ray source. µCT is a crucial tool for several scientific disciplines such as physics, biology, and chemistry.
Over the last decade, µCT has become a technique capable of not only recording 3D information but also filming dynamical processes. Several breakthroughs have made this possible: i) intense X-ray sources (synchrotron light sources), ii) efficient and fast X-ray detectors, and iii) fast 3D reconstruction algorithms. Despite all of these developments, the acquisition protocols remain unchanged, i.e., the sample is only rotated faster. This fast rotation introduces forces which may alter the studied dynamics and ultimately limit the achievable temporal resolution.
My project is to establish an X-ray microscope that avoids the sample rotation, obtaining 3D information from a single X-ray flash by splitting it into nine-angularly resolved beams which illuminate the sample simultaneously. This approach, when implemented at intense X-ray sources such as synchrotron light sources and X-ray free-electron lasers, will allow the filming of natural processes with micrometer to nanometer resolution and resolve dynamics from microseconds to femtoseconds. To demonstrate its capabilities, I will study fundamental processes in cellulose fibers, a renewable biomaterial, which can replace fossil-based materials, such as plastics. This technique will open up the possibility to film dynamics in 3D to answer questions coming from industry and natural sciences at rates not accessible today.
Max ERC Funding
1 999 213 €
Duration
Start date: 2021-03-01, End date: 2026-02-28
Project acronym ABODYFORCE
Project High Throughput Microfluidic Cell and Nanoparticle Handling by Molecular and Thermal Gradient Acoustic Focusing
Researcher (PI) Per AUGUSTSSON
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE7, ERC-2019-STG
Summary In this project we will push the limits of microscale ultrasound-based technology to gain access to diagnostically important rare constituents of blood within minutes from blood draw.
To meet the demands for shorter time from sampling to result in healthcare there is an increased interest to shift from heavy centralized lab equipment to point-of-care tests and patient self-testing. Key challenges with point-of-care equipment is to enable simultaneous measurement of many parameters at a reasonable cost and size of equipment. Therefore, microscale technologies that can take in small amounts of blood and output results within minutes are sought for. In addition, the high precision and potential for multi-stage serial processing offered by such microfluidic methods opens up for fast and automated isolation of rare cell populations, such as circulating tumor cells, and controlled high-throughput size fractionation of sub-micron biological particles, such as platelets, pathogens and extracellular vesicles.
To achieve effective and fast separation of blood components we will expose blood to acoustic radiation forces in a flow-through format. By exploiting a newly discovered acoustic body force, that stems from local variations the acoustic properties of the cell suspension, we can generate self-organizing configurations of the blood cells. We will tailor and tune the acoustic cell-organization in novel ways by time modulation of the acoustic field, by altering the acoustic properties of the fluid by solute molecules, and by exploiting a novel concept of sound interaction with thermal gradients.
The project will render new fundamental knowledge regarding the acoustic properties of single cells and an extensive theoretical framework for the response of cells in any aqueous medium, bounding geometry and sound field, potentially leading to new diagnostic methods.
Summary
In this project we will push the limits of microscale ultrasound-based technology to gain access to diagnostically important rare constituents of blood within minutes from blood draw.
To meet the demands for shorter time from sampling to result in healthcare there is an increased interest to shift from heavy centralized lab equipment to point-of-care tests and patient self-testing. Key challenges with point-of-care equipment is to enable simultaneous measurement of many parameters at a reasonable cost and size of equipment. Therefore, microscale technologies that can take in small amounts of blood and output results within minutes are sought for. In addition, the high precision and potential for multi-stage serial processing offered by such microfluidic methods opens up for fast and automated isolation of rare cell populations, such as circulating tumor cells, and controlled high-throughput size fractionation of sub-micron biological particles, such as platelets, pathogens and extracellular vesicles.
To achieve effective and fast separation of blood components we will expose blood to acoustic radiation forces in a flow-through format. By exploiting a newly discovered acoustic body force, that stems from local variations the acoustic properties of the cell suspension, we can generate self-organizing configurations of the blood cells. We will tailor and tune the acoustic cell-organization in novel ways by time modulation of the acoustic field, by altering the acoustic properties of the fluid by solute molecules, and by exploiting a novel concept of sound interaction with thermal gradients.
The project will render new fundamental knowledge regarding the acoustic properties of single cells and an extensive theoretical framework for the response of cells in any aqueous medium, bounding geometry and sound field, potentially leading to new diagnostic methods.
Max ERC Funding
1 999 720 €
Duration
Start date: 2019-11-01, End date: 2024-10-31
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 AFRODITE
Project Advanced Fluid Research On Drag reduction In Turbulence Experiments
Researcher (PI) Jens Henrik Mikael Fransson
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Country Sweden
Call Details Starting Grant (StG), PE8, ERC-2010-StG_20091028
Summary A hot topic in today's debate on global warming is drag reduction in aeronautics. The most beneficial concept for drag reduction is to maintain the major portion of the airfoil laminar. Estimations show that the potential drag reduction can be as much as 15%, which would give a significant reduction of NOx and CO emissions in the atmosphere considering that the number of aircraft take offs, only in the EU, is over 19 million per year. An important element for successful flow control, which can lead to a reduced aerodynamic drag, is enhanced physical understanding of the transition to turbulence process.
In previous wind tunnel measurements we have shown that roughness elements can be used to sensibly delay transition to turbulence. The result is revolutionary, since the common belief has been that surface roughness causes earlier transition and in turn increases the drag, and is a proof of concept of the passive control method per se. The beauty with a passive control technique is that no external energy has to be added to the flow system in order to perform the control, instead one uses the existing energy in the flow.
In this project proposal, AFRODITE, we will take this passive control method to the next level by making it twofold, more persistent and more robust. Transition prevention is the goal rather than transition delay and the method will be extended to simultaneously control separation, which is another unwanted flow phenomenon especially during airplane take offs. AFRODITE will be a catalyst for innovative research, which will lead to a cleaner sky.
Summary
A hot topic in today's debate on global warming is drag reduction in aeronautics. The most beneficial concept for drag reduction is to maintain the major portion of the airfoil laminar. Estimations show that the potential drag reduction can be as much as 15%, which would give a significant reduction of NOx and CO emissions in the atmosphere considering that the number of aircraft take offs, only in the EU, is over 19 million per year. An important element for successful flow control, which can lead to a reduced aerodynamic drag, is enhanced physical understanding of the transition to turbulence process.
In previous wind tunnel measurements we have shown that roughness elements can be used to sensibly delay transition to turbulence. The result is revolutionary, since the common belief has been that surface roughness causes earlier transition and in turn increases the drag, and is a proof of concept of the passive control method per se. The beauty with a passive control technique is that no external energy has to be added to the flow system in order to perform the control, instead one uses the existing energy in the flow.
In this project proposal, AFRODITE, we will take this passive control method to the next level by making it twofold, more persistent and more robust. Transition prevention is the goal rather than transition delay and the method will be extended to simultaneously control separation, which is another unwanted flow phenomenon especially during airplane take offs. AFRODITE will be a catalyst for innovative research, which will lead to a cleaner sky.
Max ERC Funding
1 418 399 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym AGINGSEXDIFF
Project Aging Differently: Understanding Sex Differences in Reproductive, Demographic and Functional Senescence
Researcher (PI) Alexei Maklakov
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a
long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not
only in how long they live and when they start to senesce, but also in how they react to
environmental interventions aimed at prolonging their life span or decelerating the onset of aging.
Therefore, sex differences in life span and aging have important implications beyond the questions
posed by fundamental science. Both evolutionary reasons and medical implications of sex
differences in demographic, reproductive and physiological senescence are and will be crucial
targets of present and future research in the biology of aging. Here I propose a two-step approach
that can provide a significant breakthrough in our understanding of the biological basis of sex
differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific
mortality rate in sex differences in aging by developing a series of targeted experimental
evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I
address the role of intra-locus sexual conflict in the evolution of aging by combining novel
methodology from nutritional ecology – the Geometric Framework – with artificial selection
approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will
directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the
adaptive evolution of diet choice. By combining techniques from evolutionary biology and
nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to
the training of young scientists in this rapidly developing field.
Summary
Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a
long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not
only in how long they live and when they start to senesce, but also in how they react to
environmental interventions aimed at prolonging their life span or decelerating the onset of aging.
Therefore, sex differences in life span and aging have important implications beyond the questions
posed by fundamental science. Both evolutionary reasons and medical implications of sex
differences in demographic, reproductive and physiological senescence are and will be crucial
targets of present and future research in the biology of aging. Here I propose a two-step approach
that can provide a significant breakthrough in our understanding of the biological basis of sex
differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific
mortality rate in sex differences in aging by developing a series of targeted experimental
evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I
address the role of intra-locus sexual conflict in the evolution of aging by combining novel
methodology from nutritional ecology – the Geometric Framework – with artificial selection
approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will
directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the
adaptive evolution of diet choice. By combining techniques from evolutionary biology and
nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to
the training of young scientists in this rapidly developing field.
Max ERC Funding
1 391 904 €
Duration
Start date: 2010-12-01, End date: 2016-05-31
Project acronym ANSR
Project Ab initio approach to nuclear structure and reactions (++)
Researcher (PI) Christian Erik Forssen
Host Institution (HI) CHALMERS TEKNISKA HOEGSKOLA AB
Country Sweden
Call Details Starting Grant (StG), PE2, ERC-2009-StG
Summary Today, much interest in several fields of physics is devoted to the study of small, open quantum systems, whose properties are profoundly affected by the environment; i.e., the continuum of decay channels. In nuclear physics, these problems were originally studied in the context of nuclear reactions but their importance has been reestablished with the advent of radioactive-beam physics and the resulting interest in exotic nuclei. In particular, strong theory initiatives in this area of research will be instrumental for the success of the experimental program at the Facility for Antiproton and Ion Research (FAIR) in Germany. In addition, many of the aspects of open quantum systems are also being explored in the rapidly evolving research on ultracold atomic gases, quantum dots, and other nanodevices. A first-principles description of open quantum systems presents a substantial theoretical and computational challenge. However, the current availability of enormous computing power has allowed theorists to make spectacular progress on problems that were previously thought intractable. The importance of computational methods to study quantum many-body systems is stressed in this proposal. Our approach is based on the ab initio no-core shell model (NCSM), which is a well-established theoretical framework aimed originally at an exact description of nuclear structure starting from realistic inter-nucleon forces. A successful completion of this project requires extensions of the NCSM mathematical framework and the development of highly advanced computer codes. The '++' in the project title indicates the interdisciplinary aspects of the present research proposal and the ambition to make a significant impact on connected fields of many-body physics.
Summary
Today, much interest in several fields of physics is devoted to the study of small, open quantum systems, whose properties are profoundly affected by the environment; i.e., the continuum of decay channels. In nuclear physics, these problems were originally studied in the context of nuclear reactions but their importance has been reestablished with the advent of radioactive-beam physics and the resulting interest in exotic nuclei. In particular, strong theory initiatives in this area of research will be instrumental for the success of the experimental program at the Facility for Antiproton and Ion Research (FAIR) in Germany. In addition, many of the aspects of open quantum systems are also being explored in the rapidly evolving research on ultracold atomic gases, quantum dots, and other nanodevices. A first-principles description of open quantum systems presents a substantial theoretical and computational challenge. However, the current availability of enormous computing power has allowed theorists to make spectacular progress on problems that were previously thought intractable. The importance of computational methods to study quantum many-body systems is stressed in this proposal. Our approach is based on the ab initio no-core shell model (NCSM), which is a well-established theoretical framework aimed originally at an exact description of nuclear structure starting from realistic inter-nucleon forces. A successful completion of this project requires extensions of the NCSM mathematical framework and the development of highly advanced computer codes. The '++' in the project title indicates the interdisciplinary aspects of the present research proposal and the ambition to make a significant impact on connected fields of many-body physics.
Max ERC Funding
1 304 800 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym ATMOGAIN
Project Atmospheric Gas-Aerosol Interface:
From Fundamental Theory to Global Effects
Researcher (PI) Ilona Anniina Riipinen
Host Institution (HI) STOCKHOLMS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE10, ERC-2011-StG_20101014
Summary Atmospheric aerosol particles are a major player in the earth system: they impact the climate by scattering and absorbing solar radiation, as well as regulating the properties of clouds. On regional scales aerosol particles are among the main pollutants deteriorating air quality. Capturing the impact of aerosols is one of the main challenges in understanding the driving forces behind changing climate and air quality.
Atmospheric aerosol numbers are governed by the ultrafine (< 100 nm in diameter) particles. Most of these particles have been formed from atmospheric vapours, and their fate and impacts are governed by the mass transport processes between the gas and particulate phases. These transport processes are currently poorly understood. Correct representation of the aerosol growth/shrinkage by condensation/evaporation of atmospheric vapours is thus a prerequisite for capturing the evolution and impacts of aerosols.
I propose to start a research group that will address the major current unknowns in atmospheric ultrafine particle growth and evaporation. First, we will develop a unified theoretical framework to describe the mass accommodation processes at aerosol surfaces, aiming to resolve the current ambiguity with respect to the uptake of atmospheric vapours by aerosols. Second, we will study the condensational properties of selected organic compounds and their mixtures. Organic compounds are known to contribute significantly to atmospheric aerosol growth, but the properties that govern their condensation, such as saturation vapour pressures and activities, are largely unknown. Third, we aim to resolve the gas and particulate phase processes that govern the growth of realistic atmospheric aerosol. Fourth, we will parameterize ultrafine aerosol growth, implement the parameterizations to chemical transport models, and quantify the impact of these condensation and evaporation processes on global and regional aerosol budgets.
Summary
Atmospheric aerosol particles are a major player in the earth system: they impact the climate by scattering and absorbing solar radiation, as well as regulating the properties of clouds. On regional scales aerosol particles are among the main pollutants deteriorating air quality. Capturing the impact of aerosols is one of the main challenges in understanding the driving forces behind changing climate and air quality.
Atmospheric aerosol numbers are governed by the ultrafine (< 100 nm in diameter) particles. Most of these particles have been formed from atmospheric vapours, and their fate and impacts are governed by the mass transport processes between the gas and particulate phases. These transport processes are currently poorly understood. Correct representation of the aerosol growth/shrinkage by condensation/evaporation of atmospheric vapours is thus a prerequisite for capturing the evolution and impacts of aerosols.
I propose to start a research group that will address the major current unknowns in atmospheric ultrafine particle growth and evaporation. First, we will develop a unified theoretical framework to describe the mass accommodation processes at aerosol surfaces, aiming to resolve the current ambiguity with respect to the uptake of atmospheric vapours by aerosols. Second, we will study the condensational properties of selected organic compounds and their mixtures. Organic compounds are known to contribute significantly to atmospheric aerosol growth, but the properties that govern their condensation, such as saturation vapour pressures and activities, are largely unknown. Third, we aim to resolve the gas and particulate phase processes that govern the growth of realistic atmospheric aerosol. Fourth, we will parameterize ultrafine aerosol growth, implement the parameterizations to chemical transport models, and quantify the impact of these condensation and evaporation processes on global and regional aerosol budgets.
Max ERC Funding
1 498 099 €
Duration
Start date: 2011-09-01, End date: 2016-08-31
Project acronym B-DOMINANCE
Project B Cell Immunodominance in Antiviral Immunity
Researcher (PI) Davide Angeletti
Host Institution (HI) GOETEBORGS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS6, ERC-2019-STG
Summary This proposal aims at understanding how B cell specificity and immunodominance shape primary and secondary humoral responses to influenza A virus. Influenza A virus is a relevant human pathogen causing a considerable yearly death toll and economic burden to society. Immunodominance is a major driving force of adaptive immunity and defines the hierarchical recognition of epitopes on the same antigen. Previous studies analysing B cell dynamics in primary and secondary responses have been mainly focusing on simple antigens and competition between B cell clones of the same family. Investigation using complex antigens and examining interclonal competition are surprisingly scarce. Influenza hemagglutinin (HA) is a prime candidate to study immunodominance in B cells. I have generated a set of mutant viruses that will allow for an unprecedented investigation into immunodominance and B cell interclonal competition in primary and secondary responses. These viruses can be used to isolate and enumerate antibody and B cells specific for different epitopes on the same complex antigen (HA). I will use these unique tools in combination with state-of-the-art immunological methods, multi-colour flow cytometry and single cells RNA sequencing paired with B cell receptor sequencing to gain fundamental insights into B cell regulation and anti-viral humoral responses. I will i) study the link between B cell receptor characteristics, specificity and B cell fate decisions in primary responses, ii) characterize the relative contribution of pre-existing B cells, serum antibodies and CD4 T cells for immunodominance of secondary responses, iii) define immunodominance in human individuals, repeatedly exposed to influenza virus. I expect this project to critically improve our understanding of basic B cell biology with the long-term benefit of improving current vaccination against variable viral pathogens.
Summary
This proposal aims at understanding how B cell specificity and immunodominance shape primary and secondary humoral responses to influenza A virus. Influenza A virus is a relevant human pathogen causing a considerable yearly death toll and economic burden to society. Immunodominance is a major driving force of adaptive immunity and defines the hierarchical recognition of epitopes on the same antigen. Previous studies analysing B cell dynamics in primary and secondary responses have been mainly focusing on simple antigens and competition between B cell clones of the same family. Investigation using complex antigens and examining interclonal competition are surprisingly scarce. Influenza hemagglutinin (HA) is a prime candidate to study immunodominance in B cells. I have generated a set of mutant viruses that will allow for an unprecedented investigation into immunodominance and B cell interclonal competition in primary and secondary responses. These viruses can be used to isolate and enumerate antibody and B cells specific for different epitopes on the same complex antigen (HA). I will use these unique tools in combination with state-of-the-art immunological methods, multi-colour flow cytometry and single cells RNA sequencing paired with B cell receptor sequencing to gain fundamental insights into B cell regulation and anti-viral humoral responses. I will i) study the link between B cell receptor characteristics, specificity and B cell fate decisions in primary responses, ii) characterize the relative contribution of pre-existing B cells, serum antibodies and CD4 T cells for immunodominance of secondary responses, iii) define immunodominance in human individuals, repeatedly exposed to influenza virus. I expect this project to critically improve our understanding of basic B cell biology with the long-term benefit of improving current vaccination against variable viral pathogens.
Max ERC Funding
1 481 697 €
Duration
Start date: 2019-12-01, End date: 2024-11-30
Project acronym BIOFINDER
Project New biomarkers for Alzheimer’s & Parkinson’s diseases - key tools for early diagnosis and drug development
Researcher (PI) Oskar Hansson
Host Institution (HI) MAX IV Laboratory, Lund University
Country Sweden
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
Summary Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity.
AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets.
We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays.
New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging
Summary
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity.
AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets.
We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays.
New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging
Max ERC Funding
1 500 000 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
