Project acronym 3D-VIEW
Project Seeing the invisible: Light-based 3D imaging of opaque nanostructures
Researcher (PI) Stefan WITTE
Host Institution (HI) STICHTING NEDERLANDSE WETENSCHAPPELIJK ONDERZOEK INSTITUTEN
Country Netherlands
Call Details Consolidator Grant (CoG), PE7, ERC-2019-COG
Summary Nanostructures drive the world around us. Every modern electronic device contains integrated circuits and nano-electronics to provide its functionality. Advances in nanotechnology directly impact society by enabling smartphones, autonomous devices, the internet of things, data storage, and essentially all forms of advanced technology. Fabricating such nanostructures crucially depends on having the tools to make them visible without destroying them. Modern nanodevices often have complex three-dimensional architectures with small features in all dimensions. While imaging methods that achieve nanometer-scale resolution exist, there are currently no compact tools that can look inside 3D nanostructures made out of metals and semiconductors without damaging their delicate internal structure. I will address this challenge by developing compact tools to image 3D nanostructures in a non-invasive way. Even though most nanostructures are completely opaque to visible light, I will develop light-based methods, combined with computational imaging techniques developed in my previous ERC project, to look inside them with unprecedented resolution and contrast. Light-based imaging is unparalleled in speed and versatility, and allows contact-free detection. My proposal is to: 1) Use compact laser-produced soft-X-ray sources to image nanostructures with high 3D resolution and element-sensitive contrast; 2) Use laser-induced ultrasound pulses to image complex 3D nanostructures, even through strongly absorbing materials; 3) Employ computational imaging methods to reconstruct high-resolution 3D object images from the resulting complex diffraction signals. I will forge a coordinated research program to bring these concepts to reality. This program provides exciting prospects for fundamental science and industrial metrology. I will go beyond the state-of-the-art in nano-imaging, to extend our vision into the complex interior of the smallest structures found in science and technology.
Summary
Nanostructures drive the world around us. Every modern electronic device contains integrated circuits and nano-electronics to provide its functionality. Advances in nanotechnology directly impact society by enabling smartphones, autonomous devices, the internet of things, data storage, and essentially all forms of advanced technology. Fabricating such nanostructures crucially depends on having the tools to make them visible without destroying them. Modern nanodevices often have complex three-dimensional architectures with small features in all dimensions. While imaging methods that achieve nanometer-scale resolution exist, there are currently no compact tools that can look inside 3D nanostructures made out of metals and semiconductors without damaging their delicate internal structure. I will address this challenge by developing compact tools to image 3D nanostructures in a non-invasive way. Even though most nanostructures are completely opaque to visible light, I will develop light-based methods, combined with computational imaging techniques developed in my previous ERC project, to look inside them with unprecedented resolution and contrast. Light-based imaging is unparalleled in speed and versatility, and allows contact-free detection. My proposal is to: 1) Use compact laser-produced soft-X-ray sources to image nanostructures with high 3D resolution and element-sensitive contrast; 2) Use laser-induced ultrasound pulses to image complex 3D nanostructures, even through strongly absorbing materials; 3) Employ computational imaging methods to reconstruct high-resolution 3D object images from the resulting complex diffraction signals. I will forge a coordinated research program to bring these concepts to reality. This program provides exciting prospects for fundamental science and industrial metrology. I will go beyond the state-of-the-art in nano-imaging, to extend our vision into the complex interior of the smallest structures found in science and technology.
Max ERC Funding
2 000 000 €
Duration
Start date: 2020-10-01, End date: 2025-09-30
Project acronym A.L.I.B.I.
Project Helping Children to Make the Best of their Transition to High School
Researcher (PI) Pol VAN LIER
Host Institution (HI) STICHTING VU
Country Netherlands
Call Details Proof of Concept (PoC), ERC-2019-PoC
Summary Poor social experiences with peers, such as peer rejection or peer victimization, and with teachers, such as receiving low support or having conflictual relations with teachers during elementary school impede children’s self- and stress-regulation. The affected self- and stress-regulation places these children at risk of developing similar troublesome relations with teachers and peers after the transition to high school.
We propose to develop a serious game named A.L.I.B.I. to help children make a successful transition from elementary school to high school. In A.L.I.B.I. children play in a virtual high school environment. The objective of A.L.I.B.I. is to uncover an alien, who is disguised as a teacher or peer. By engaging in prosocial interactions with teachers and peers, by taking the perspective of others, by learning to overthink multiple response options before acting, and by valuing long term perspectives over short term goals, children will receive clues that will help them to uncover the alien.
The advantage of A.L.I.B.I. is that through the use of a virtual school environment, it provides children a realistic yet safe environment to learn and rehearse prosocial behaviors, to prepare them for the new social environment. In addition, A.L.I.B.I. is intuitively attractive for children, through its use of game elements and presentation on a tablet computer. The proposed ERC PoC grant has the goal to (1) develop A.L.I.B.I. into a stand-alone serious game that will be ready for implementation, (2) to test the effectiveness of A.L.I.B.I., (3) to integrate A.L.I.B.I. in ongoing school transition trainings as provided by three school counseling organizations in three regions in The Netherlands, and (4) to develop a marketing strategy for broader Dutch and European implementation.
Summary
Poor social experiences with peers, such as peer rejection or peer victimization, and with teachers, such as receiving low support or having conflictual relations with teachers during elementary school impede children’s self- and stress-regulation. The affected self- and stress-regulation places these children at risk of developing similar troublesome relations with teachers and peers after the transition to high school.
We propose to develop a serious game named A.L.I.B.I. to help children make a successful transition from elementary school to high school. In A.L.I.B.I. children play in a virtual high school environment. The objective of A.L.I.B.I. is to uncover an alien, who is disguised as a teacher or peer. By engaging in prosocial interactions with teachers and peers, by taking the perspective of others, by learning to overthink multiple response options before acting, and by valuing long term perspectives over short term goals, children will receive clues that will help them to uncover the alien.
The advantage of A.L.I.B.I. is that through the use of a virtual school environment, it provides children a realistic yet safe environment to learn and rehearse prosocial behaviors, to prepare them for the new social environment. In addition, A.L.I.B.I. is intuitively attractive for children, through its use of game elements and presentation on a tablet computer. The proposed ERC PoC grant has the goal to (1) develop A.L.I.B.I. into a stand-alone serious game that will be ready for implementation, (2) to test the effectiveness of A.L.I.B.I., (3) to integrate A.L.I.B.I. in ongoing school transition trainings as provided by three school counseling organizations in three regions in The Netherlands, and (4) to develop a marketing strategy for broader Dutch and European implementation.
Max ERC Funding
150 000 €
Duration
Start date: 2020-08-01, End date: 2022-01-31
Project acronym ACQUIRE
Project Assessing cardiac Contractility and Quantification of Underlying mechanisms In vitro via Response in Excitation-contraction coupling
Researcher (PI) Christine MUMMERY
Host Institution (HI) ACADEMISCH ZIEKENHUIS LEIDEN
Country Netherlands
Call Details Proof of Concept (PoC), ERC-2019-PoC
Summary "Academia and industry urgently needs reliable models to study heart failure and toxic effects of drugs on the heart. While new models based on human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are now emerging, accurate readouts of cardiomyocyte function fall short of needs. Apart from improving the models biologically, more sensitive, informative and accurate readouts are needed to detect abnormal cardiomyocyte behaviour. Several tools have proven their ability to assess electrical changes or calcium handling in hiPSC-CMs, but they are typically incompatible with 3D tissue models and moreover, there is paucity of appropriate tools to quantify the most important function of myocardium: contraction. Our ERC Advanced Grant STEMCARDIOVASC entailed the development of improved tools for cardiac functionality. One of the most important bioassays developed as an outcome of STEMCARDIOVASC was the Triple Transient Measurement (TTM) System. The TTM System quantifies electrical activity, intracellular calcium flux and contractility simultaneously and is our answer to the challenge of pharma in understanding when and how drugs or diseases affect cardiac contractility using hiPSC-CM models. In this ERC Proof of Concept project “ACQUIRE”, we strive to bring the TTM to a commercial applicable service, and later product. To reach this goal we have set out four aims to come to a Minimum Viable Product: i) increase the flexibility of the system to accommodate a larger variety of optical probes, ii) increase the throughput of the system to compete with current measurement systems, iii) increase user friendliness by integrating software modules for running and analysing measurements and iv) define a route for commercialisation.
Resulting from ""ACQUIRE"" the TTM System can be commercialized as a human cardiac based 3-in-1 assay for cardiotoxicity testing and a novel tool for providing mechanistic insight in the EC coupling for disease modelling and drug discovery."
Summary
"Academia and industry urgently needs reliable models to study heart failure and toxic effects of drugs on the heart. While new models based on human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are now emerging, accurate readouts of cardiomyocyte function fall short of needs. Apart from improving the models biologically, more sensitive, informative and accurate readouts are needed to detect abnormal cardiomyocyte behaviour. Several tools have proven their ability to assess electrical changes or calcium handling in hiPSC-CMs, but they are typically incompatible with 3D tissue models and moreover, there is paucity of appropriate tools to quantify the most important function of myocardium: contraction. Our ERC Advanced Grant STEMCARDIOVASC entailed the development of improved tools for cardiac functionality. One of the most important bioassays developed as an outcome of STEMCARDIOVASC was the Triple Transient Measurement (TTM) System. The TTM System quantifies electrical activity, intracellular calcium flux and contractility simultaneously and is our answer to the challenge of pharma in understanding when and how drugs or diseases affect cardiac contractility using hiPSC-CM models. In this ERC Proof of Concept project “ACQUIRE”, we strive to bring the TTM to a commercial applicable service, and later product. To reach this goal we have set out four aims to come to a Minimum Viable Product: i) increase the flexibility of the system to accommodate a larger variety of optical probes, ii) increase the throughput of the system to compete with current measurement systems, iii) increase user friendliness by integrating software modules for running and analysing measurements and iv) define a route for commercialisation.
Resulting from ""ACQUIRE"" the TTM System can be commercialized as a human cardiac based 3-in-1 assay for cardiotoxicity testing and a novel tool for providing mechanistic insight in the EC coupling for disease modelling and drug discovery."
Max ERC Funding
150 000 €
Duration
Start date: 2020-09-01, End date: 2022-02-28
Project acronym AEONS
Project Advancing the Equation of state of Neutron Stars
Researcher (PI) Anna WATTS
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Consolidator Grant (CoG), PE9, ERC-2019-COG
Summary Densities in neutron star (NS) cores can reach up to ten times the density of a normal atomic nucleus, and the stabilising effect of gravitational confinement permits long-timescale weak interactions. This generates nucleonic matter that is extremely neutron-rich, and the exciting possibility of stable states of strange matter (hyperons or deconfined quarks). Our uncertainty about the nature of cold ultradense matter is encoded in the Equation of State (EOS), which can be mapped via the stellar structure equations to quantities like mass M and radius R that determine the exterior space-time.
One very promising technique for measuring the EOS exploits hotspots that form on the NS surface due to the pulsar mechanism, accretion streams, or during thermonuclear explosions in the stellar ocean. As the NS rotates, the hotspot gives rise to a pulsation and relativistic effects encode information about the EOS into the pulse profile. Pulse Profile Modelling (PPM), which employs relativistic ray-tracing and Bayesian inference codes to measure M-R and the EOS, is being pioneered by NASA’s NICER telescope, which is poised to deliver its first results in 2019.
Complexities, that have only become apparent with exposure to real data, mean that there is work to be done if we are to have confidence in the nominal 5-10% accuracy of NICER’s M-R results. AEONS will deliver this. The project will also look ahead to the next generation of large-area X-ray timing telescopes, since it is only then that PPM will place tight constraints on dense matter models. The sources these missions target, accreting neutron stars, pose challenges for PPM such as variability, surface pattern uncertainty, and polarimetric signatures. AEONS will develop a robust pipeline for accreting NS PPM and embed it in a multi-messenger EOS inference framework with radio and gravitational wave constraints. This will ensure that PPM delivers major advances in our understanding of the nature of matter.
Summary
Densities in neutron star (NS) cores can reach up to ten times the density of a normal atomic nucleus, and the stabilising effect of gravitational confinement permits long-timescale weak interactions. This generates nucleonic matter that is extremely neutron-rich, and the exciting possibility of stable states of strange matter (hyperons or deconfined quarks). Our uncertainty about the nature of cold ultradense matter is encoded in the Equation of State (EOS), which can be mapped via the stellar structure equations to quantities like mass M and radius R that determine the exterior space-time.
One very promising technique for measuring the EOS exploits hotspots that form on the NS surface due to the pulsar mechanism, accretion streams, or during thermonuclear explosions in the stellar ocean. As the NS rotates, the hotspot gives rise to a pulsation and relativistic effects encode information about the EOS into the pulse profile. Pulse Profile Modelling (PPM), which employs relativistic ray-tracing and Bayesian inference codes to measure M-R and the EOS, is being pioneered by NASA’s NICER telescope, which is poised to deliver its first results in 2019.
Complexities, that have only become apparent with exposure to real data, mean that there is work to be done if we are to have confidence in the nominal 5-10% accuracy of NICER’s M-R results. AEONS will deliver this. The project will also look ahead to the next generation of large-area X-ray timing telescopes, since it is only then that PPM will place tight constraints on dense matter models. The sources these missions target, accreting neutron stars, pose challenges for PPM such as variability, surface pattern uncertainty, and polarimetric signatures. AEONS will develop a robust pipeline for accreting NS PPM and embed it in a multi-messenger EOS inference framework with radio and gravitational wave constraints. This will ensure that PPM delivers major advances in our understanding of the nature of matter.
Max ERC Funding
2 425 000 €
Duration
Start date: 2020-06-01, End date: 2025-05-31
Project acronym ALPHA
Project Assessing Legacies of Past Human Activities in Amazonia
Researcher (PI) Crystal MCMICHAEL
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Starting Grant (StG), LS8, ERC-2019-STG
Summary Amazon forests contribute vital ecosystem services, including maintaining biodiversity (>10,000 tree species) and storing large amounts of carbon. Amazonia also features prominently in global climate, carbon, and vegetation models, which assume tropical forests are effectively pristine and that past human disturbance mimicked natural processes. It is now evident that recurrent human disturbance of Amazonia, like fire and deforestation, were significant in some areas. Since those disturbances likely modify subsequent vegetation dynamics - including temporarily increasing forest capacity to absorb carbon - the emerging paradigm of human disturbance is a challenge to global ecological understanding. The focus of my project is thus to reliably determine whether human disturbances occurred in locations that form the basis of global models. A key expected outcome is to either legitimize or force revision to these models of carbon sequestration potential in Amazonia.
I will innovatively integrate ecological, paleoecological, archaeological, chemical and biogeographic analyses to assess the degree to which past human disturbance drives the diversity patterns and carbon dynamics observed in modern Amazonian forests. For key long-term sites across Amazonia, I will quantify the: i) time since the last fire, ii) past fire frequency, extent and intensity, iii) past vegetation change in the presence and absence of human activity, and iv) continuity of past human activity over the last 1000 years. My results will provide the first quantification of local-scale recovery processes exceeding 100 years in tropical forests, and will determine if observed forest dynamics are driven by disturbances that occurred before modern ecological surveys began. I will then quantify the extent to which past disturbances create an overestimation of carbon storage potential, driving a profound reexamination of carbon sequestration and biodiversity patterns in Amazonia.
Summary
Amazon forests contribute vital ecosystem services, including maintaining biodiversity (>10,000 tree species) and storing large amounts of carbon. Amazonia also features prominently in global climate, carbon, and vegetation models, which assume tropical forests are effectively pristine and that past human disturbance mimicked natural processes. It is now evident that recurrent human disturbance of Amazonia, like fire and deforestation, were significant in some areas. Since those disturbances likely modify subsequent vegetation dynamics - including temporarily increasing forest capacity to absorb carbon - the emerging paradigm of human disturbance is a challenge to global ecological understanding. The focus of my project is thus to reliably determine whether human disturbances occurred in locations that form the basis of global models. A key expected outcome is to either legitimize or force revision to these models of carbon sequestration potential in Amazonia.
I will innovatively integrate ecological, paleoecological, archaeological, chemical and biogeographic analyses to assess the degree to which past human disturbance drives the diversity patterns and carbon dynamics observed in modern Amazonian forests. For key long-term sites across Amazonia, I will quantify the: i) time since the last fire, ii) past fire frequency, extent and intensity, iii) past vegetation change in the presence and absence of human activity, and iv) continuity of past human activity over the last 1000 years. My results will provide the first quantification of local-scale recovery processes exceeding 100 years in tropical forests, and will determine if observed forest dynamics are driven by disturbances that occurred before modern ecological surveys began. I will then quantify the extent to which past disturbances create an overestimation of carbon storage potential, driving a profound reexamination of carbon sequestration and biodiversity patterns in Amazonia.
Max ERC Funding
1 481 378 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym Bac2MUC
Project Bacteria-mucin interactions – Shaping intestinal epithelial responses in health and disease
Researcher (PI) Karin STRIJBIS
Host Institution (HI) UNIVERSITEIT UTRECHT
Country Netherlands
Call Details Starting Grant (StG), LS6, ERC-2019-STG
Summary The intestinal microbiota consists of beneficial commensal bacteria and pathobionts that cause inflammation. The intestinal mucus layer dictates how specific members of the microbiota affect health and disease. The mucus layer consists of soluble mucins and epithelial transmembrane (TM) mucins that regulate host responses. The molecular mechanisms as to how the intestinal microbiota affect the functions of TM mucins is largely unknown. My recent work shows that TM mucin MUC1 is a key receptor for Salmonella invasion into polarized epithelial cells. We also discovered that MUC13 is a central regulator of epithelial barrier formation. I hypothesize that bacteria-mucin interactions shape epithelial responses by stimulating healthy barrier formation, driving inflammation or mediating bacterial invasion. My aim is to unravel molecular mechanisms via which distinct bacterial species regulate the functions of TM mucins MUC1 and MUC13 in the intestine. The key objectives of Bac2MUC are to: 1. Identify commensal and pathogenic bacteria that target TM mucins 2. Elucidate TM mucin signaling pathways activated by commensal and pathogenic bacteria 3. Determine the function of TM mucins during inflammation and invasion 4. Utilize bacteria-TM mucin interactions to unravel healthy epithelial barrier regulation I will use an innovative large-scale screening platform to identify novel bacteria-mucin interactions. TM mucin signaling pathways during bacterial interaction will be characterized by sortase technology. Cutting-edge technologies such as CRISPR/Cas9 genome editing and advanced microscopy will be applied in established bacterial infection assays with intestinal cell lines and organoids. Bac2MUC is an ambitious and ground-breaking project that will address, for the first time, the complex interplay between intestinal bacteria and TM mucins. This project will contribute to clinical strategies that prevent intestinal inflammation and improve mucosal barrier function.
Summary
The intestinal microbiota consists of beneficial commensal bacteria and pathobionts that cause inflammation. The intestinal mucus layer dictates how specific members of the microbiota affect health and disease. The mucus layer consists of soluble mucins and epithelial transmembrane (TM) mucins that regulate host responses. The molecular mechanisms as to how the intestinal microbiota affect the functions of TM mucins is largely unknown. My recent work shows that TM mucin MUC1 is a key receptor for Salmonella invasion into polarized epithelial cells. We also discovered that MUC13 is a central regulator of epithelial barrier formation. I hypothesize that bacteria-mucin interactions shape epithelial responses by stimulating healthy barrier formation, driving inflammation or mediating bacterial invasion. My aim is to unravel molecular mechanisms via which distinct bacterial species regulate the functions of TM mucins MUC1 and MUC13 in the intestine. The key objectives of Bac2MUC are to: 1. Identify commensal and pathogenic bacteria that target TM mucins 2. Elucidate TM mucin signaling pathways activated by commensal and pathogenic bacteria 3. Determine the function of TM mucins during inflammation and invasion 4. Utilize bacteria-TM mucin interactions to unravel healthy epithelial barrier regulation I will use an innovative large-scale screening platform to identify novel bacteria-mucin interactions. TM mucin signaling pathways during bacterial interaction will be characterized by sortase technology. Cutting-edge technologies such as CRISPR/Cas9 genome editing and advanced microscopy will be applied in established bacterial infection assays with intestinal cell lines and organoids. Bac2MUC is an ambitious and ground-breaking project that will address, for the first time, the complex interplay between intestinal bacteria and TM mucins. This project will contribute to clinical strategies that prevent intestinal inflammation and improve mucosal barrier function.
Max ERC Funding
1 500 000 €
Duration
Start date: 2020-03-01, End date: 2025-02-28
Project acronym BOOTCAMP
Project Boosting metabolism in T cells: a tool to improve T cell therapy for chronic lymphocytic leukemia patients
Researcher (PI) Aron Philip KATER
Host Institution (HI) ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Consolidator Grant (CoG), LS7, ERC-2019-COG
Summary Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Novel targeted drugs are effective, but not curative. Moreover, prolonged use is associated with development of resistance, toxicity, and high economic cost. Allogeneic stem cell transplantation, which evokes a T cell mediated response, is potentially curative yet is associated with high graft-vs-host-related mortality. Therefore, an autologous T cell-based approach, e.g. chimeric antigen receptor T cells (CAR-T), is a highly promising strategy. However, in contrast to the success of CAR-T cells in aggressive leukemia, their effect in CLL is limited owing to a largely unexplained acquired T cell dysfunction in this disease setting.
I recently found that CLL cells impose a reduction in mitochondrial fitness and altered glucose metabolism on T cells, which may underlie the acquired T cell dysfunction. Lending clinical significance to this finding, I observed that the success of CAR-T treatment in CLL patients is highly associated with their mitochondrial biogenic capacity. I therefore hypothesize that improving mitochondrial fitness of CAR-T cells may offer a path to cure CLL.
I aim to:
1. Characterize the molecular mechanisms of metabolic alterations in CLL-derived T cells
2. Elucidate how CLL cells reprogram T cells metabolism
3. Increase mitochondrial biogenesis and fitness in CAR-T cells to improve therapeutic efficacy
To achieve these goals, I will conduct an array of complementary molecular, metabolic, and genetic assays using patient samples and a murine model of CLL. To address therapeutic potential I will study murine and human CAR-T cells in which metabolic processes will be manipulated.
This project provides crucial insight into the interplay between CLL and T cells, and the underlying failure of cancer immune surveillance. This may lead to metabolism-based curative autologous T cell based therapies in CLL, which may also be relevant for other malignancies.
Summary
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Novel targeted drugs are effective, but not curative. Moreover, prolonged use is associated with development of resistance, toxicity, and high economic cost. Allogeneic stem cell transplantation, which evokes a T cell mediated response, is potentially curative yet is associated with high graft-vs-host-related mortality. Therefore, an autologous T cell-based approach, e.g. chimeric antigen receptor T cells (CAR-T), is a highly promising strategy. However, in contrast to the success of CAR-T cells in aggressive leukemia, their effect in CLL is limited owing to a largely unexplained acquired T cell dysfunction in this disease setting.
I recently found that CLL cells impose a reduction in mitochondrial fitness and altered glucose metabolism on T cells, which may underlie the acquired T cell dysfunction. Lending clinical significance to this finding, I observed that the success of CAR-T treatment in CLL patients is highly associated with their mitochondrial biogenic capacity. I therefore hypothesize that improving mitochondrial fitness of CAR-T cells may offer a path to cure CLL.
I aim to:
1. Characterize the molecular mechanisms of metabolic alterations in CLL-derived T cells
2. Elucidate how CLL cells reprogram T cells metabolism
3. Increase mitochondrial biogenesis and fitness in CAR-T cells to improve therapeutic efficacy
To achieve these goals, I will conduct an array of complementary molecular, metabolic, and genetic assays using patient samples and a murine model of CLL. To address therapeutic potential I will study murine and human CAR-T cells in which metabolic processes will be manipulated.
This project provides crucial insight into the interplay between CLL and T cells, and the underlying failure of cancer immune surveillance. This may lead to metabolism-based curative autologous T cell based therapies in CLL, which may also be relevant for other malignancies.
Max ERC Funding
1 997 662 €
Duration
Start date: 2020-08-01, End date: 2025-07-31
Project acronym BREAST4D
Project 4D Breast Imaging for Personalized Breast Cancer Treatment
Researcher (PI) Ioannis SECHOPOULOS
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Country Netherlands
Call Details Consolidator Grant (CoG), LS7, ERC-2019-COG
Summary The next major step forward in the fight against breast cancer will be the introduction of personalized treatment. Such a precision medicine approach would maximize the rate of complete response, minimize ineffective therapy and morbidity, and eliminate the need for localized breast cancer surgery.
To achieve this, I will create a novel functional imaging modality, 4D dynamic contrast enhanced dedicated breast computed tomography (4D DCE-BCT), capable of characterizing every different genomic, molecular, and physiologic region present in a breast tumor. 4D DCE-BCT will involve putting together the hardware necessary for the continuous acquisition of x-ray breast projections with advanced techniques, for a period of minutes. Combined with new image reconstruction, correction, and processing algorithms, these acquisitions will result in quantitatively accurate 4D images of breast perfusion, with voxels thousands of times smaller, and a temporal resolution 27x and a limiting spatial resolution 6x higher than those in current imaging modalities. Radiomics-based analysis of these images will allow me to fully identify and characterize the tumor heterogeneity, known to result in regions with different therapy resistance.
Complete characterization of the tumor will allow for optimal neoadjuvant treatment planning, maximizing the probability of achieving pathologic complete response (pCR) and minimizing the risk of recurrence. Due to its relative affordability and safety, the use of 4D DCE-BCT for treatment response monitoring throughout treatment will be possible, making treatment adjustments possible, if needed. Finally, I envision that 4D DCE-BCT will be able to predict and determine that pCR is achieved, making surgery to excise any remnant viable tumor cells unnecessary.
The next era in breast cancer treatment is patient-specific care. The advanced imaging developed and introduced in this project will usher in this new era.
Summary
The next major step forward in the fight against breast cancer will be the introduction of personalized treatment. Such a precision medicine approach would maximize the rate of complete response, minimize ineffective therapy and morbidity, and eliminate the need for localized breast cancer surgery.
To achieve this, I will create a novel functional imaging modality, 4D dynamic contrast enhanced dedicated breast computed tomography (4D DCE-BCT), capable of characterizing every different genomic, molecular, and physiologic region present in a breast tumor. 4D DCE-BCT will involve putting together the hardware necessary for the continuous acquisition of x-ray breast projections with advanced techniques, for a period of minutes. Combined with new image reconstruction, correction, and processing algorithms, these acquisitions will result in quantitatively accurate 4D images of breast perfusion, with voxels thousands of times smaller, and a temporal resolution 27x and a limiting spatial resolution 6x higher than those in current imaging modalities. Radiomics-based analysis of these images will allow me to fully identify and characterize the tumor heterogeneity, known to result in regions with different therapy resistance.
Complete characterization of the tumor will allow for optimal neoadjuvant treatment planning, maximizing the probability of achieving pathologic complete response (pCR) and minimizing the risk of recurrence. Due to its relative affordability and safety, the use of 4D DCE-BCT for treatment response monitoring throughout treatment will be possible, making treatment adjustments possible, if needed. Finally, I envision that 4D DCE-BCT will be able to predict and determine that pCR is achieved, making surgery to excise any remnant viable tumor cells unnecessary.
The next era in breast cancer treatment is patient-specific care. The advanced imaging developed and introduced in this project will usher in this new era.
Max ERC Funding
2 308 393 €
Duration
Start date: 2020-06-01, End date: 2025-05-31
Project acronym BuBble Gun
Project Penetrating microjets in soft substrates: towards controlled needle-free injections
Researcher (PI) David FERNANDEZ RIVAS
Host Institution (HI) UNIVERSITEIT TWENTE
Country Netherlands
Call Details Starting Grant (StG), PE8, ERC-2019-STG
Summary The needle-free delivery of liquid jets into soft and heterogeneous substrates, e.g. human tissue, has been hindered by (1) the need to reach specific penetration depths with energy efficient means, (2) the break-up of jets that impedes control over the dose delivery, and (3) liquid splash-back after impacting the substrate that cause cross-contamination between injections. BuBble Gun is aimed at overcoming these challenges. My team and I have recently uncovered new operational regimes of cavitation with continuous-wave lasers. My next goal is to study the energy partition between the creation of bubbles, the formation of liquid jets, and the penetration of these jets into soft substrates. Fundamental insights on energy partitioning will then be applied to achieve major breakthroughs in jet injection, by (1) controlling cavitation within microfluidic confinement, (2) tuning the rheology of jets emerging from confined cavitation, and (3) deriving the relationships between fluid dynamics and material properties governing jet injection into soft substrates. I expect to advance the knowledge at the intersection of microfluidics, physics, and bioengineering, to enable unprecedented control over cavitation, jetting, and injection phenomena. We will develop a portable energy- efficient injection platform by using ultra-high-speed imaging, and quantifying injections with experimental resolutions below the microsecond and micrometer scales. The rheological properties of the jets will be tuned with biocompatible additives to ensure cohesion, before injecting them into in-vitro targets and ex-vivo skin. Numerical models will assist untangling the influence of microfluidic configuration and material properties on the injection outcomes. The ultimate result will be the predictable, reproducible, and efficient injection of liquids that will enable a wide-range of technologies, such as additive manufacturing, coating modifications, the delivery of drugs and vaccinations.
Summary
The needle-free delivery of liquid jets into soft and heterogeneous substrates, e.g. human tissue, has been hindered by (1) the need to reach specific penetration depths with energy efficient means, (2) the break-up of jets that impedes control over the dose delivery, and (3) liquid splash-back after impacting the substrate that cause cross-contamination between injections. BuBble Gun is aimed at overcoming these challenges. My team and I have recently uncovered new operational regimes of cavitation with continuous-wave lasers. My next goal is to study the energy partition between the creation of bubbles, the formation of liquid jets, and the penetration of these jets into soft substrates. Fundamental insights on energy partitioning will then be applied to achieve major breakthroughs in jet injection, by (1) controlling cavitation within microfluidic confinement, (2) tuning the rheology of jets emerging from confined cavitation, and (3) deriving the relationships between fluid dynamics and material properties governing jet injection into soft substrates. I expect to advance the knowledge at the intersection of microfluidics, physics, and bioengineering, to enable unprecedented control over cavitation, jetting, and injection phenomena. We will develop a portable energy- efficient injection platform by using ultra-high-speed imaging, and quantifying injections with experimental resolutions below the microsecond and micrometer scales. The rheological properties of the jets will be tuned with biocompatible additives to ensure cohesion, before injecting them into in-vitro targets and ex-vivo skin. Numerical models will assist untangling the influence of microfluidic configuration and material properties on the injection outcomes. The ultimate result will be the predictable, reproducible, and efficient injection of liquids that will enable a wide-range of technologies, such as additive manufacturing, coating modifications, the delivery of drugs and vaccinations.
Max ERC Funding
1 500 000 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym BuildingTomorrow
Project Building a Better Tomorrow: Development Knowledge and Practice in Central Asia and Beyond, 1970-2017
Researcher (PI) Artemy KALINOVSKY
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Consolidator Grant (CoG), SH6, ERC-2019-COG
Summary The landscape of post-Soviet Central Asia (Tajikistan, Uzbekistan, Kyrygzstan, Kazakhstan, Turkmenistan) is littered with the physical remnants of Soviet development, both positive –health clinics and schools – and negative - decaying factories, polluted soil, and dried out rivers. Less visible are Soviet development’s political, intellectual, and institutional legacies. Yet just as post-socialist states and international development organizations have been forced to deal with the physical legacies of socialism, their approaches to economic development, welfare provision, and governance has been shaped by the socialist past. After the collapse of the USSR in 1991, the newly independent states of Central Asia invited international institutions and foreign donors to help them achieve prosperity and transition to a market economy. At the time, most development institutions and national governments subscribed to the so-called “Washington Consensus” which emphasized financial discipline, minimum state regulation, and open borders. This project proposes to study the influence of Central Asian economists, activists, specialists, and government officials who straddled the Soviet/post-Soviet divide by going to work in national and international development institutions after independence. By studying these individuals and the legacies of their work will allow us to investigate how ideas and practices of economic development and welfare provision were shaped and reshaped at the local and international level. The project will uncover how international development transformed post-Soviet Central Asia, and how the encounter with post-socialist states transformed paradigms and practices of international development. The research will thus make an innovative scholarly contribution to understanding the legacy of socialism, the history of economic development, and the the global history of development.
Summary
The landscape of post-Soviet Central Asia (Tajikistan, Uzbekistan, Kyrygzstan, Kazakhstan, Turkmenistan) is littered with the physical remnants of Soviet development, both positive –health clinics and schools – and negative - decaying factories, polluted soil, and dried out rivers. Less visible are Soviet development’s political, intellectual, and institutional legacies. Yet just as post-socialist states and international development organizations have been forced to deal with the physical legacies of socialism, their approaches to economic development, welfare provision, and governance has been shaped by the socialist past. After the collapse of the USSR in 1991, the newly independent states of Central Asia invited international institutions and foreign donors to help them achieve prosperity and transition to a market economy. At the time, most development institutions and national governments subscribed to the so-called “Washington Consensus” which emphasized financial discipline, minimum state regulation, and open borders. This project proposes to study the influence of Central Asian economists, activists, specialists, and government officials who straddled the Soviet/post-Soviet divide by going to work in national and international development institutions after independence. By studying these individuals and the legacies of their work will allow us to investigate how ideas and practices of economic development and welfare provision were shaped and reshaped at the local and international level. The project will uncover how international development transformed post-Soviet Central Asia, and how the encounter with post-socialist states transformed paradigms and practices of international development. The research will thus make an innovative scholarly contribution to understanding the legacy of socialism, the history of economic development, and the the global history of development.
Max ERC Funding
1 997 605 €
Duration
Start date: 2020-05-01, End date: 2025-04-30
