Project acronym ARMOR-T
Project Armoring multifunctional T cells for cancer therapy
Researcher (PI) Sebastian Kobold
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Adoptive T cell therapy (ACT) is a powerful approach to treat even advanced cancer diseases where poor prognosis calls for innovative treatments. However ACT is critically limited by insufficient T cell infiltration into the tumor, T cell activation at the tumor site and local T cell suppression. Few advances have been made in the field to tackle these limitations besides increasing T cell activation. My group has focussed on these unaddressed issues but came to realise that tackling these one by one will not be sufficient. I have developed a panel of unpublished chemokine receptors and innovative modular antibody-activated receptors which have the potential to overcome the limitations of ACT against solid tumors. This ground-breaking portfolio places my group in the unique position to address combination of synergistic receptors and enable cellular therapies in previously unsuccessful indications. My project will provide the rationale for provision of an effective cancer treatment. The goal is to develop the next generation of ACT through T cell engineering both by forced expression of migratory and activating receptors and simultaneous deletion of immune suppressive molecules by gene editing. ARMOR-T will provide the basis for further preclinical and clinical development of a pioneering cellular product devoid of the limitations of available products to date. I will prove 1) synergy between migratory and modular activating receptors, 2) feasibility to integrate gene editing into a T cell expansion protocol, 3) synergy between gene editing, migratory and modular receptors and 4) efficacy, safety and mode of action. The main work of the project will be carried out in models of pancreatic cancer. The ARMOR-T platform will subsequently be translated to other cancer entities where response to ACT is likely such as melanoma, breast or colon cancer, providing less toxic and more effective therapies to otherwise untreatable disease.
Summary
Adoptive T cell therapy (ACT) is a powerful approach to treat even advanced cancer diseases where poor prognosis calls for innovative treatments. However ACT is critically limited by insufficient T cell infiltration into the tumor, T cell activation at the tumor site and local T cell suppression. Few advances have been made in the field to tackle these limitations besides increasing T cell activation. My group has focussed on these unaddressed issues but came to realise that tackling these one by one will not be sufficient. I have developed a panel of unpublished chemokine receptors and innovative modular antibody-activated receptors which have the potential to overcome the limitations of ACT against solid tumors. This ground-breaking portfolio places my group in the unique position to address combination of synergistic receptors and enable cellular therapies in previously unsuccessful indications. My project will provide the rationale for provision of an effective cancer treatment. The goal is to develop the next generation of ACT through T cell engineering both by forced expression of migratory and activating receptors and simultaneous deletion of immune suppressive molecules by gene editing. ARMOR-T will provide the basis for further preclinical and clinical development of a pioneering cellular product devoid of the limitations of available products to date. I will prove 1) synergy between migratory and modular activating receptors, 2) feasibility to integrate gene editing into a T cell expansion protocol, 3) synergy between gene editing, migratory and modular receptors and 4) efficacy, safety and mode of action. The main work of the project will be carried out in models of pancreatic cancer. The ARMOR-T platform will subsequently be translated to other cancer entities where response to ACT is likely such as melanoma, breast or colon cancer, providing less toxic and more effective therapies to otherwise untreatable disease.
Max ERC Funding
1 636 710 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym ATOM
Project Advanced Holographic Tomographies for Nanoscale Materials: Revealing Electromagnetic and Deformation Fields, Chemical Composition and Quantum States at Atomic Resolution.
Researcher (PI) Axel LUBK
Host Institution (HI) LEIBNIZ-INSTITUT FUER FESTKOERPER- UND WERKSTOFFFORSCHUNG DRESDEN E.V.
Call Details Starting Grant (StG), PE3, ERC-2016-STG
Summary The ongoing miniaturization in nanotechnology and functional materials puts an ever increasing focus on the development of three-dimensional (3D) nanostructures, such as quantum dot arrays, structured nanowires, or non-trivial topological magnetic textures such as skyrmions, which permit a better performance of logical or memory devices in terms of speed and energy efficiency. To develop and advance such technologies and to improve the understanding of the underlying fundamental solid state physics effects, the nondestructive and quantitative 3D characterization of physical, e.g., electric or magnetic, fields down to atomic resolution is indispensable. Current nanoscale metrology methods only inadequately convey this information, e.g., because they probe surfaces, record projections, or lack resolution. AToM will provide a ground-breaking tomographic methodology for current nanotechnology by mapping electric and magnetic fields as well as crucial properties of the underlying atomic structure in solids, such as the chemical composition, mechanical strain or spin configuration in 3D down to atomic resolution. To achieve that goal, advanced holographic and tomographic setups in the Transmission Electron Microscope (TEM) are combined with novel computational methods, e.g., taking into account the ramifications of electron diffraction. Moreover, fundamental application limits are overcome (A) by extending the holographic principle, requiring coherent electron beams, to quantum state reconstructions applicable to electrons of any (in)coherence; and (B) by adapting a unique in-situ TEM with a very large sample chamber to facilitate holographic field sensing down to very low temperatures (6 K) under application of external, e.g., electric, stimuli. The joint development of AToM in response to current problems of nanotechnology, including the previously mentioned ones, is anticipated to immediately and sustainably advance nanotechnology in its various aspects.
Summary
The ongoing miniaturization in nanotechnology and functional materials puts an ever increasing focus on the development of three-dimensional (3D) nanostructures, such as quantum dot arrays, structured nanowires, or non-trivial topological magnetic textures such as skyrmions, which permit a better performance of logical or memory devices in terms of speed and energy efficiency. To develop and advance such technologies and to improve the understanding of the underlying fundamental solid state physics effects, the nondestructive and quantitative 3D characterization of physical, e.g., electric or magnetic, fields down to atomic resolution is indispensable. Current nanoscale metrology methods only inadequately convey this information, e.g., because they probe surfaces, record projections, or lack resolution. AToM will provide a ground-breaking tomographic methodology for current nanotechnology by mapping electric and magnetic fields as well as crucial properties of the underlying atomic structure in solids, such as the chemical composition, mechanical strain or spin configuration in 3D down to atomic resolution. To achieve that goal, advanced holographic and tomographic setups in the Transmission Electron Microscope (TEM) are combined with novel computational methods, e.g., taking into account the ramifications of electron diffraction. Moreover, fundamental application limits are overcome (A) by extending the holographic principle, requiring coherent electron beams, to quantum state reconstructions applicable to electrons of any (in)coherence; and (B) by adapting a unique in-situ TEM with a very large sample chamber to facilitate holographic field sensing down to very low temperatures (6 K) under application of external, e.g., electric, stimuli. The joint development of AToM in response to current problems of nanotechnology, including the previously mentioned ones, is anticipated to immediately and sustainably advance nanotechnology in its various aspects.
Max ERC Funding
1 499 602 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym AUTO-EVO
Project Autonomous DNA Evolution in a Molecule Trap
Researcher (PI) Dieter Braun
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), PE3, ERC-2010-StG_20091028
Summary How can we create molecular life in the lab?
That is, can we drive evolvable DNA/RNA-machines under a simple nonequilibrium setting? We will trigger basic forms
of autonomous Darwinian evolution by implementing replication, mutation and selection on the molecular level in a single
micro-chamber? We will explore protein-free replication schemes to tackle the Eigen-Paradox of replication and translation
under archaic nonequilibrium settings. The conditions mimic thermal gradients in porous rock near hydrothermal vents on the
early earth. We are in a unique position to pursue these questions due to our previous inventions of convective replication,
optothermal molecule traps and light driven microfluidics. Four interconnected strategies are pursued ranging from basic
replication using tRNA-like hairpins, entropic cooling or UV degradation down to protein-based DNA evolution in a trap, all
with biotechnological applications. The approach is risky, however very interesting physics and biology on the way. We will:
(i) Replicate DNA with continuous, convective PCR in the selection of a thermal molecule trap
(ii) Replicate sequences with metastable, tRNA-like hairpins exponentially
(iii) Build DNA complexes by structure-selective trapping to replicate by entropic decay
(iv) Drive replication by Laser-based UV degradation
Both replication and trapping are exponential processes, yielding in combination a highly nonlinear dynamics. We proceed
along publishable steps and implement highly efficient modes of continuous molecular evolution. As shown in the past, we
will create biotechnological applications from basic scientific questions (see our NanoTemper Startup). The starting grant will
allow us to compete with Jack Szostak who very recently picked up our approach [JACS 131, 9628 (2009)].
Summary
How can we create molecular life in the lab?
That is, can we drive evolvable DNA/RNA-machines under a simple nonequilibrium setting? We will trigger basic forms
of autonomous Darwinian evolution by implementing replication, mutation and selection on the molecular level in a single
micro-chamber? We will explore protein-free replication schemes to tackle the Eigen-Paradox of replication and translation
under archaic nonequilibrium settings. The conditions mimic thermal gradients in porous rock near hydrothermal vents on the
early earth. We are in a unique position to pursue these questions due to our previous inventions of convective replication,
optothermal molecule traps and light driven microfluidics. Four interconnected strategies are pursued ranging from basic
replication using tRNA-like hairpins, entropic cooling or UV degradation down to protein-based DNA evolution in a trap, all
with biotechnological applications. The approach is risky, however very interesting physics and biology on the way. We will:
(i) Replicate DNA with continuous, convective PCR in the selection of a thermal molecule trap
(ii) Replicate sequences with metastable, tRNA-like hairpins exponentially
(iii) Build DNA complexes by structure-selective trapping to replicate by entropic decay
(iv) Drive replication by Laser-based UV degradation
Both replication and trapping are exponential processes, yielding in combination a highly nonlinear dynamics. We proceed
along publishable steps and implement highly efficient modes of continuous molecular evolution. As shown in the past, we
will create biotechnological applications from basic scientific questions (see our NanoTemper Startup). The starting grant will
allow us to compete with Jack Szostak who very recently picked up our approach [JACS 131, 9628 (2009)].
Max ERC Funding
1 487 827 €
Duration
Start date: 2010-08-01, End date: 2015-07-31
Project acronym BILUM
Project Novel applications based on organic biluminescence
Researcher (PI) Sebastian Reineke
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Call Details Starting Grant (StG), PE3, ERC-2015-STG
Summary Organic semiconducting molecules often make for very good luminescent materials. Fundamental excitations are localized on single molecules, which is in stark contrast to inorganic semiconductors, such that exchange interactions lead to energetically distinct singlet and triplet states. The singlet-excited state is the origin of conventional fluorescence. However, once an excitation is in the molecular triplet state, emission of photons is very unlikely, because spin conservation needs to be broken. Here, non-radiative recombination outcompetes the radiative.
Recent research efforts led to the discovery of highly efficient biluminescence. Here, in addition to the fluorescence from the singlet state, the phosphorescence (triplet state emission) is unlocked by suppression of non-radiative channels at room temperature. The dynamics of both states is vastly different with nanosecond fluorescence and millisecond phosphorescence. If both channels are highly luminescent, then there is no room for loss channels.
Within BILUM, the virtually unexplored phenomenon of biluminescence will be the central point: On the basic science side, efforts will be focussed on the detailed understanding of structure-property relationships that are key for efficient dual state emission. At the same time, with a curiosity driven engineering approach, known bilumophores will be carefully tested in different scenarios to set the ground for future applications. Biluminescence has the potential to access non-radiative triplet states that are in many cases system limiting, to serve as ultra-broadband emitters, to introduce persistent (ultra long-lived) emission, to store photonic energy, and to allow optical sensing with internal reference emission – all on the molecular level. New bilumophores will be identified through systematic screening that will employ quantum chemical calculations and developed through organic synthesis.
Summary
Organic semiconducting molecules often make for very good luminescent materials. Fundamental excitations are localized on single molecules, which is in stark contrast to inorganic semiconductors, such that exchange interactions lead to energetically distinct singlet and triplet states. The singlet-excited state is the origin of conventional fluorescence. However, once an excitation is in the molecular triplet state, emission of photons is very unlikely, because spin conservation needs to be broken. Here, non-radiative recombination outcompetes the radiative.
Recent research efforts led to the discovery of highly efficient biluminescence. Here, in addition to the fluorescence from the singlet state, the phosphorescence (triplet state emission) is unlocked by suppression of non-radiative channels at room temperature. The dynamics of both states is vastly different with nanosecond fluorescence and millisecond phosphorescence. If both channels are highly luminescent, then there is no room for loss channels.
Within BILUM, the virtually unexplored phenomenon of biluminescence will be the central point: On the basic science side, efforts will be focussed on the detailed understanding of structure-property relationships that are key for efficient dual state emission. At the same time, with a curiosity driven engineering approach, known bilumophores will be carefully tested in different scenarios to set the ground for future applications. Biluminescence has the potential to access non-radiative triplet states that are in many cases system limiting, to serve as ultra-broadband emitters, to introduce persistent (ultra long-lived) emission, to store photonic energy, and to allow optical sensing with internal reference emission – all on the molecular level. New bilumophores will be identified through systematic screening that will employ quantum chemical calculations and developed through organic synthesis.
Max ERC Funding
1 462 500 €
Duration
Start date: 2016-04-01, End date: 2021-03-31
Project acronym BIO-IRT
Project Biologically individualized, model-based radiotherapy on the basis of multi-parametric molecular tumour profiling
Researcher (PI) Daniela Thorwarth
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Call Details Starting Grant (StG), LS7, ERC-2013-StG
Summary High precision radiotherapy (RT) allows extremely flexible tumour treatments achieving highly conformal radiation doses while sparing surrounding organs at risk. Nevertheless, failure rates of up to 50% are reported for head and neck cancer (HNC) due to radiation resistance induced by pathophysiologic factors such as hypoxia and other clinical factors as HPV-status, stage and tumour volume.
This project aims at developing a multi-parametric model for individualized RT (iRT) dose prescriptions in HNC based on biological markers and functional PET/MR imaging. This project goes far beyond current research standards and clinical practice as it aims for establishing hypoxia PET and f-MRI as well as biological markers in HNC as a role model for a novel concept from anatomy-based to biologically iRT.
During this project, a multi-parametric model will be developed on a preclinical basis that combines biological markers such as different oncogenes and hypoxia gene classifier with functional PET/MR imaging, such as FMISO PET in combination with different f-MRI techniques, like DW-, DCE- and BOLD-MRI in addition to MR spectroscopy. The ultimate goal of this project is a multi-parametric model to predict therapy outcome and guide iRT.
In a second part, a clinical study will be carried out to validate the preclinical model in patients. Based on the most informative radiobiological and imaging parameters as identified during the pre-clinical phase, biological markers and advanced PET/MR imaging will be evaluated in terms of their potential for iRT dose prescription.
Successful development of a model for biologically iRT prescription on the basis of multi-parametric molecular profiling would provide a unique basis for personalized cancer treatment. A validated multi-parametric model for RT outcome would represent a paradigm shift from anatomy-based to biologically iRT concepts with the ultimate goal of improving cancer cure rates.
Summary
High precision radiotherapy (RT) allows extremely flexible tumour treatments achieving highly conformal radiation doses while sparing surrounding organs at risk. Nevertheless, failure rates of up to 50% are reported for head and neck cancer (HNC) due to radiation resistance induced by pathophysiologic factors such as hypoxia and other clinical factors as HPV-status, stage and tumour volume.
This project aims at developing a multi-parametric model for individualized RT (iRT) dose prescriptions in HNC based on biological markers and functional PET/MR imaging. This project goes far beyond current research standards and clinical practice as it aims for establishing hypoxia PET and f-MRI as well as biological markers in HNC as a role model for a novel concept from anatomy-based to biologically iRT.
During this project, a multi-parametric model will be developed on a preclinical basis that combines biological markers such as different oncogenes and hypoxia gene classifier with functional PET/MR imaging, such as FMISO PET in combination with different f-MRI techniques, like DW-, DCE- and BOLD-MRI in addition to MR spectroscopy. The ultimate goal of this project is a multi-parametric model to predict therapy outcome and guide iRT.
In a second part, a clinical study will be carried out to validate the preclinical model in patients. Based on the most informative radiobiological and imaging parameters as identified during the pre-clinical phase, biological markers and advanced PET/MR imaging will be evaluated in terms of their potential for iRT dose prescription.
Successful development of a model for biologically iRT prescription on the basis of multi-parametric molecular profiling would provide a unique basis for personalized cancer treatment. A validated multi-parametric model for RT outcome would represent a paradigm shift from anatomy-based to biologically iRT concepts with the ultimate goal of improving cancer cure rates.
Max ERC Funding
1 370 799 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym BIOSENSORIMAGING
Project Hyperpolarized Biosensors in Molecular Imaging
Researcher (PI) Leif Schröder
Host Institution (HI) FORSCHUNGSVERBUND BERLIN EV
Call Details Starting Grant (StG), LS7, ERC-2009-StG
Summary Xenon biosensors have an outstanding potential to increase the significance of magnetic resonance imaging (MRI) in molecular imaging and to combine the advantages of MRI with the high sensitivity of hyperpolarized Xe-129 and the specificity of a functionalized contrast agent. Based on new detection schemes (Hyper-CEST method) in Xe MRI, this novel concept in molecular diagnostics will be made available for biomedical applications. The advancement focuses on high-sensitivity in vitro diagnostics for localization of tumour cells in cell cultures and first demonstrations on animal models based on a transferrin-functionalized biosensor. Such a sensor will enable detection of subcutaneous tumours at high sensitivity without any background signal. More detailed work on the different available Hyper-CEST contrast parameters focuses on an absolute quantification of new molecular markers that will improve non-invasive tumour diagnostics significantly. NMR detection of functionalized Xe biosensors have the potential to close the sensitivity gap between modalities of nuclear medicine like PET/SPECT and MRI without using ionizing radiation or making compromises in penetration depth like in optical methods.
Summary
Xenon biosensors have an outstanding potential to increase the significance of magnetic resonance imaging (MRI) in molecular imaging and to combine the advantages of MRI with the high sensitivity of hyperpolarized Xe-129 and the specificity of a functionalized contrast agent. Based on new detection schemes (Hyper-CEST method) in Xe MRI, this novel concept in molecular diagnostics will be made available for biomedical applications. The advancement focuses on high-sensitivity in vitro diagnostics for localization of tumour cells in cell cultures and first demonstrations on animal models based on a transferrin-functionalized biosensor. Such a sensor will enable detection of subcutaneous tumours at high sensitivity without any background signal. More detailed work on the different available Hyper-CEST contrast parameters focuses on an absolute quantification of new molecular markers that will improve non-invasive tumour diagnostics significantly. NMR detection of functionalized Xe biosensors have the potential to close the sensitivity gap between modalities of nuclear medicine like PET/SPECT and MRI without using ionizing radiation or making compromises in penetration depth like in optical methods.
Max ERC Funding
1 848 600 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym BREATHE
Project Biochemically modified messenger RNA encoding nucleases for in vivo gene correction of severe inherited lung diseases
Researcher (PI) Michael Kormann
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Call Details Starting Grant (StG), LS7, ERC-2014-STG
Summary Surfactant Protein B (SP-B) deficiency and Cystic Fibrosis (CF) are severe, fatal inherited diseases affecting the lungs of ten thousands of people, for which there is currently no available cure. Although gene therapy is a promising therapeutic approach, various technical problems, including numerous physical and immune-mediated barriers, have prevented successful application to date. My recent studies were the first to demonstrate the life-saving efficacy of repeated pulmonary delivery of chemically modified messenger RNA (mRNA) in a mouse model of congenital SP-B deficiency. By incorporating balanced amounts of modified nucleotides to mimic endogenous transcripts, I developed a safe and therapeutically efficient vehicle for lung transfection that eliminates the risk of genomic integration commonly associated with DNA-based vectors. I also assessed the delivery of mRNA-encoded site-specific nucleases to the lung to facilitate targeted gene correction of the underlying disease-causing mutations. In comprehensive studies, we show that a single application of nucleases encoded by nucleotide-modified RNA (nec-mRNA) can generate in vivo correction of terminally differentiated alveolar type II cells, which more than quadrupled the life span of SP-B deficient mice. Together with my working group, I aim to further develop this technology to enhance the efficiency and safety of nec-mRNA-mediated in vivo lung stem cell targeting, providing an ultimate cure by permanent correction. Specifically, we will test this approach in humanized mouse models of SP-B deficiency and CF. Developing and genetically engineering humanized models in vivo will be a critical step towards the safe translation of mRNA based nuclease technology to the clinic. With my competitive edge in lung-transfection technology and strong data, I feel that my group is uniquely suited to achieve these goals and to make a highly valuable contribution to the development of an efficient treatment.
Summary
Surfactant Protein B (SP-B) deficiency and Cystic Fibrosis (CF) are severe, fatal inherited diseases affecting the lungs of ten thousands of people, for which there is currently no available cure. Although gene therapy is a promising therapeutic approach, various technical problems, including numerous physical and immune-mediated barriers, have prevented successful application to date. My recent studies were the first to demonstrate the life-saving efficacy of repeated pulmonary delivery of chemically modified messenger RNA (mRNA) in a mouse model of congenital SP-B deficiency. By incorporating balanced amounts of modified nucleotides to mimic endogenous transcripts, I developed a safe and therapeutically efficient vehicle for lung transfection that eliminates the risk of genomic integration commonly associated with DNA-based vectors. I also assessed the delivery of mRNA-encoded site-specific nucleases to the lung to facilitate targeted gene correction of the underlying disease-causing mutations. In comprehensive studies, we show that a single application of nucleases encoded by nucleotide-modified RNA (nec-mRNA) can generate in vivo correction of terminally differentiated alveolar type II cells, which more than quadrupled the life span of SP-B deficient mice. Together with my working group, I aim to further develop this technology to enhance the efficiency and safety of nec-mRNA-mediated in vivo lung stem cell targeting, providing an ultimate cure by permanent correction. Specifically, we will test this approach in humanized mouse models of SP-B deficiency and CF. Developing and genetically engineering humanized models in vivo will be a critical step towards the safe translation of mRNA based nuclease technology to the clinic. With my competitive edge in lung-transfection technology and strong data, I feel that my group is uniquely suited to achieve these goals and to make a highly valuable contribution to the development of an efficient treatment.
Max ERC Funding
1 497 125 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym CATALIGHT
Project Exploiting Energy Flow in Plasmonic-Catalytic Colloids
Researcher (PI) Emiliano CORTÉS
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), PE3, ERC-2018-STG
Summary The aim of CATALIGHT is to use sunlight as a source of energy in order to trigger chemical reactions by harvesting photons with plasmonic nanoparticles and channelling the energy into catalytic materials. Plasmonic-catalytic devices would allow efficient harvest, transport, and injection of solar energy into molecules. To achieve this, imaging the energy flow at the nanoscale will be crucial for establishing the true potential of plasmonics, both in the context of yielding fundamental knowledge about the light-into-chemical energy conversion processes, and for moving from active towards efficient reactive devices within nanoscale environments.
CATALIGHT has roots in three underlying components, making this project an interwoven effort to break new grounds in a crucial field for the further development of nanoscale energy manipulation: A) Super-resolution imaging of the energy-flow at the nanoscale – with a view to unravel the most efficient mechanisms to guide solar energy into catalytic materials using plasmonic structures as photon harvesters. B) Scaling-up this process through the fabrication of hierarchical photocatalytic colloids – using image-learning for the design of colloidal sources for energy manipulation. C) Light-into-chemical energy conversion – boosting efficiencies in environmental and industrial catalytic processes using tailored photocatalysts.
The outcomes of this project will not only yield a substantial amount of fundamental knowledge in these crucial areas for the further development of the field, but also provide directly exploitable results for the applied sciences, particularly photocatalysis and fuel cells.
Summary
The aim of CATALIGHT is to use sunlight as a source of energy in order to trigger chemical reactions by harvesting photons with plasmonic nanoparticles and channelling the energy into catalytic materials. Plasmonic-catalytic devices would allow efficient harvest, transport, and injection of solar energy into molecules. To achieve this, imaging the energy flow at the nanoscale will be crucial for establishing the true potential of plasmonics, both in the context of yielding fundamental knowledge about the light-into-chemical energy conversion processes, and for moving from active towards efficient reactive devices within nanoscale environments.
CATALIGHT has roots in three underlying components, making this project an interwoven effort to break new grounds in a crucial field for the further development of nanoscale energy manipulation: A) Super-resolution imaging of the energy-flow at the nanoscale – with a view to unravel the most efficient mechanisms to guide solar energy into catalytic materials using plasmonic structures as photon harvesters. B) Scaling-up this process through the fabrication of hierarchical photocatalytic colloids – using image-learning for the design of colloidal sources for energy manipulation. C) Light-into-chemical energy conversion – boosting efficiencies in environmental and industrial catalytic processes using tailored photocatalysts.
The outcomes of this project will not only yield a substantial amount of fundamental knowledge in these crucial areas for the further development of the field, but also provide directly exploitable results for the applied sciences, particularly photocatalysis and fuel cells.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym CellInspired
Project Mechanotransduction mediating cell adhesion - towards cell-inspired adaptive materials
Researcher (PI) Christine Johanna Maria Selhuber-Unkel
Host Institution (HI) CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL
Call Details Starting Grant (StG), PE3, ERC-2013-StG
Summary Adhesion is a key event for eukaryotic cells to establish contact with the extracellular matrix and other cells. It allows cells to quickly adapt to mechanical changes in their environment by either adhesion reinforcement or release. Understanding and mimicking the interplay between adhesion reinforcement and release could result in novel cell-inspired adaptive materials. In order to ultimately be able to transfer functional principles of cell adhesion to a next generation of biomimetic materials, we will elucidate the biophysics of cell adhesion in response to external force. We have already obtained important results that have provided new insights into cell adhesion. For example, we have found that the nanoscale spacing of adhesion sites controls cell adhesion reinforcement. With the project proposed here I want to advance our understanding of cell adhesion by generating a comprehensive model of mechanotransduction-mediated cell adhesion. Therefore, my group will develop new force measurement methods based on atomic force microscopy and 2D force sensor arrays that allow for a systematic investigation of key parameters in the cell adhesion system, including the concept of cellular mechanosensing. My hypothesis is that there is a transition between adhesion reinforcement and release as a function of external mechanical stress, stress history, and the biofunctionalization of the adhesive surface. Transferring our biophysical knowledge into materials science promises new materials with a dynamic adaptive mechanical and adhesion response. This transfer of biological concepts into cell-inspired materials will follow the construction principles of cells: the proposed material will be based on polymer fibers that are reversibly cross-linked and reinforce adhesion upon mechanical stress. The ultimate goal of the proposed project is to develop an intelligent polymer material with an adaptive adhesive and mechanical response similar to that found in living cells.
Summary
Adhesion is a key event for eukaryotic cells to establish contact with the extracellular matrix and other cells. It allows cells to quickly adapt to mechanical changes in their environment by either adhesion reinforcement or release. Understanding and mimicking the interplay between adhesion reinforcement and release could result in novel cell-inspired adaptive materials. In order to ultimately be able to transfer functional principles of cell adhesion to a next generation of biomimetic materials, we will elucidate the biophysics of cell adhesion in response to external force. We have already obtained important results that have provided new insights into cell adhesion. For example, we have found that the nanoscale spacing of adhesion sites controls cell adhesion reinforcement. With the project proposed here I want to advance our understanding of cell adhesion by generating a comprehensive model of mechanotransduction-mediated cell adhesion. Therefore, my group will develop new force measurement methods based on atomic force microscopy and 2D force sensor arrays that allow for a systematic investigation of key parameters in the cell adhesion system, including the concept of cellular mechanosensing. My hypothesis is that there is a transition between adhesion reinforcement and release as a function of external mechanical stress, stress history, and the biofunctionalization of the adhesive surface. Transferring our biophysical knowledge into materials science promises new materials with a dynamic adaptive mechanical and adhesion response. This transfer of biological concepts into cell-inspired materials will follow the construction principles of cells: the proposed material will be based on polymer fibers that are reversibly cross-linked and reinforce adhesion upon mechanical stress. The ultimate goal of the proposed project is to develop an intelligent polymer material with an adaptive adhesive and mechanical response similar to that found in living cells.
Max ERC Funding
1 467 483 €
Duration
Start date: 2013-09-01, End date: 2018-08-31
Project acronym COMBIOSCOPY
Project Computational Biophotonics for Endoscopic Cancer Diagnosis and Therapy
Researcher (PI) Lena Maier-Hein
Host Institution (HI) DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Call Details Starting Grant (StG), LS7, ERC-2014-STG
Summary Key challenges in endoscopic tumor diagnosis and therapy consist of the detection and discrimination of malignant tissue as well as the precise navigation of medical instruments. Currently, a low level of sensitivity and specificity in tumor detection and lack of global orientation lead to both over- and undertreatment, tumor recurrence, intra-operative complications, and high costs. The goal of this multidisciplinary project is to revolutionize clinical endoscopic imaging based on the systematic integration of two new but independant fields of research up until this point: Biophotonics and computer-assisted interventions (COMputational BIOphotonics in endoSCOPY).
For the first time, quantitative multi-modal imaging biomarkers based on structural and functional data are being developed to enhance the physician’s view by providing information that cannot be seen with the naked eye. To this extent, white light images co-registered with multispectral optical and photoacoustic images will be processed in a combined manner to dynamically reconstruct not only the visible surface in 3D but also subsurface anatomical and functional detail such as 3D vessel topology, blood volume and oxygenation. Spatio-temporal registration of multi-modal data acquired before and during the procedure will enable (1) the highly specific local tissue classification and discrimination based on tissue shape, texture, function and radiological contrast imagery as well as (2) global context-aware instrument guidance.
This innovative approach to radiation-free real-time imaging will be implemented and evaluated by means of computer-assisted colonoscopy and laparoscopy. The potential socioeconomic impact of providing high precision minimally-invasive tumor diagnosis and therapy at low cost is extremely high.
Summary
Key challenges in endoscopic tumor diagnosis and therapy consist of the detection and discrimination of malignant tissue as well as the precise navigation of medical instruments. Currently, a low level of sensitivity and specificity in tumor detection and lack of global orientation lead to both over- and undertreatment, tumor recurrence, intra-operative complications, and high costs. The goal of this multidisciplinary project is to revolutionize clinical endoscopic imaging based on the systematic integration of two new but independant fields of research up until this point: Biophotonics and computer-assisted interventions (COMputational BIOphotonics in endoSCOPY).
For the first time, quantitative multi-modal imaging biomarkers based on structural and functional data are being developed to enhance the physician’s view by providing information that cannot be seen with the naked eye. To this extent, white light images co-registered with multispectral optical and photoacoustic images will be processed in a combined manner to dynamically reconstruct not only the visible surface in 3D but also subsurface anatomical and functional detail such as 3D vessel topology, blood volume and oxygenation. Spatio-temporal registration of multi-modal data acquired before and during the procedure will enable (1) the highly specific local tissue classification and discrimination based on tissue shape, texture, function and radiological contrast imagery as well as (2) global context-aware instrument guidance.
This innovative approach to radiation-free real-time imaging will be implemented and evaluated by means of computer-assisted colonoscopy and laparoscopy. The potential socioeconomic impact of providing high precision minimally-invasive tumor diagnosis and therapy at low cost is extremely high.
Max ERC Funding
1 499 699 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
