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 BioMNP
Project Understanding the interaction between metal nanoparticles and biological membranes
Researcher (PI) Giulia Rossi
Host Institution (HI) UNIVERSITA DEGLI STUDI DI GENOVA
Country Italy
Call Details Starting Grant (StG), PE3, ERC-2015-STG
Summary The BioMNP objective is the molecular-level understanding of the interactions between surface functionalized metal nanoparticles and biological membranes, by means of cutting-edge computational techniques and new molecular models.
Metal nanoparticles (NP) play more and more important roles in pharmaceutical and medical technology as diagnostic or therapeutic devices. Metal NPs can nowadays be engineered in a multitude of shapes, sizes and compositions, and they can be decorated with an almost infinite variety of functionalities. Despite such technological advances, there is still poor understanding of the molecular processes that drive the interactions of metal NPs with cells. Cell membranes are the first barrier encountered by NPs entering living organisms. The understanding and control of the interaction of nanoparticles with biological membranes is therefore of paramount importance to understand the molecular basis of the NP biological effects.
BioMNP will go beyond the state of the art by rationalizing the complex interplay of NP size, composition, functionalization and aggregation state during the interaction with model biomembranes. Membranes, in turn, will be modelled at an increasing level of complexity in terms of lipid composition and phase. BioMNP will rely on cutting-edge simulation techniques and facilities, and develop new coarse-grained models grounded on finer-level atomistic simulations, to study the NP-membrane interactions on an extremely large range of length and time scales.
BioMNP will benefit from important and complementary experimental collaborations, will propose interpretations of the available experimental data and make predictions to guide the design of functional, non-toxic metal nanoparticles for biomedical applications. BioMNP aims at answering fundamental questions at the crossroads of physics, biology and chemistry. Its results will have an impact on nanomedicine, toxicology, nanotechnology and material sciences.
Summary
The BioMNP objective is the molecular-level understanding of the interactions between surface functionalized metal nanoparticles and biological membranes, by means of cutting-edge computational techniques and new molecular models.
Metal nanoparticles (NP) play more and more important roles in pharmaceutical and medical technology as diagnostic or therapeutic devices. Metal NPs can nowadays be engineered in a multitude of shapes, sizes and compositions, and they can be decorated with an almost infinite variety of functionalities. Despite such technological advances, there is still poor understanding of the molecular processes that drive the interactions of metal NPs with cells. Cell membranes are the first barrier encountered by NPs entering living organisms. The understanding and control of the interaction of nanoparticles with biological membranes is therefore of paramount importance to understand the molecular basis of the NP biological effects.
BioMNP will go beyond the state of the art by rationalizing the complex interplay of NP size, composition, functionalization and aggregation state during the interaction with model biomembranes. Membranes, in turn, will be modelled at an increasing level of complexity in terms of lipid composition and phase. BioMNP will rely on cutting-edge simulation techniques and facilities, and develop new coarse-grained models grounded on finer-level atomistic simulations, to study the NP-membrane interactions on an extremely large range of length and time scales.
BioMNP will benefit from important and complementary experimental collaborations, will propose interpretations of the available experimental data and make predictions to guide the design of functional, non-toxic metal nanoparticles for biomedical applications. BioMNP aims at answering fundamental questions at the crossroads of physics, biology and chemistry. Its results will have an impact on nanomedicine, toxicology, nanotechnology and material sciences.
Max ERC Funding
1 131 250 €
Duration
Start date: 2016-04-01, End date: 2021-11-30
Project acronym CFS modelling
Project Chromosomal Common Fragile Sites: Unravelling their biological functions and the basis of their instability
Researcher (PI) Andres Joaquin Lopez-Contreras
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Country Spain
Call Details Starting Grant (StG), LS4, ERC-2015-STG
Summary Cancer and other diseases are driven by genomic alterations initiated by DNA breaks. Within our genomes, some regions are particularly prone to breakage, and these are known as common fragile sites (CFSs). CFSs are present in every person and are frequently sites of oncogenic chromosomal rearrangements. Intriguingly, despite their fragility, many CFSs are well conserved through evolution, suggesting that these regions have important physiological functions that remain elusive. My previous background in genome editing, proteomics and replication-born DNA damage has given me the tools to propose an ambitious and comprehensive plan that tackles fundamental questions on the biology of CFSs. First, we will perform a systematic analysis of the function of CFSs. Most of the CFSs contain very large genes, which has made technically difficult to dissect whether the CFS role is due to the locus itself or to the encoded gene product. However, the emergence of the CRISPR/Cas9 technology now enables the study of CFSs on a more systematic basis. We will pioneer the engineering of mammalian models harbouring large deletions at CFS loci to investigate their physiological functions at the cellular and organism levels. For those CFSs that contain genes, the cDNAs will be re-introduced at a distal locus. Using this strategy, we will be able to achieve the first comprehensive characterization of CFS roles. Second, we will develop novel targeted approaches to interrogate the chromatin-bound proteome of CFSs and its dynamics during DNA replication. Finally, and given that CFS fragility is influenced both by cell cycle checkpoints and dNTP availability, we will use mouse models to study the impact of ATR/CHK1 pathway and dNTP levels on CFS instability and cancer. Taken together, I propose an ambitious, yet feasible, project to functionally annotate and characterise these poorly understood regions of the human genome, with important potential implications for improving human health.
Summary
Cancer and other diseases are driven by genomic alterations initiated by DNA breaks. Within our genomes, some regions are particularly prone to breakage, and these are known as common fragile sites (CFSs). CFSs are present in every person and are frequently sites of oncogenic chromosomal rearrangements. Intriguingly, despite their fragility, many CFSs are well conserved through evolution, suggesting that these regions have important physiological functions that remain elusive. My previous background in genome editing, proteomics and replication-born DNA damage has given me the tools to propose an ambitious and comprehensive plan that tackles fundamental questions on the biology of CFSs. First, we will perform a systematic analysis of the function of CFSs. Most of the CFSs contain very large genes, which has made technically difficult to dissect whether the CFS role is due to the locus itself or to the encoded gene product. However, the emergence of the CRISPR/Cas9 technology now enables the study of CFSs on a more systematic basis. We will pioneer the engineering of mammalian models harbouring large deletions at CFS loci to investigate their physiological functions at the cellular and organism levels. For those CFSs that contain genes, the cDNAs will be re-introduced at a distal locus. Using this strategy, we will be able to achieve the first comprehensive characterization of CFS roles. Second, we will develop novel targeted approaches to interrogate the chromatin-bound proteome of CFSs and its dynamics during DNA replication. Finally, and given that CFS fragility is influenced both by cell cycle checkpoints and dNTP availability, we will use mouse models to study the impact of ATR/CHK1 pathway and dNTP levels on CFS instability and cancer. Taken together, I propose an ambitious, yet feasible, project to functionally annotate and characterise these poorly understood regions of the human genome, with important potential implications for improving human health.
Max ERC Funding
1 499 711 €
Duration
Start date: 2016-05-01, End date: 2022-07-31
Project acronym ChemBioAP
Project Elucidation of autophagy using novel chemical probes
Researcher (PI) Yaowen Wu
Host Institution (HI) UMEA UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS1, ERC-2015-STG
Summary The interest on autophagy, an evolutionarily conserved process in eukaryotes, has enormously increased in the last years, since autophagy is involved in many diseases such as cancer and neurodegenerative disorders. Autophagosome formation is the key process in autophagy. Despite extensive work, the model of autophagosome formation is not yet well established. Some important questions on autophagosome biogenesis remain to be elusive, such as where the bona fide marker protein of autophagosome, LC3, is lipidated, how lipidated LC3 functions in autophagosome formation, and how the proteins for LC3 lipidation and delipidation are involved in autophagosome formation. Although genetic approaches have been useful to identify genes involved in autophagy, they are chronic and thereby the dynamics of phenotypic change cannot be followed, making them not suited for study highly dynamic process such as autophagosome formation. Herein, I propose to develop and use novel chemical probes to address these issues. First, I plan to prepare semi-synthetic caged LC3 proteins and apply them to monitor dynamics of autophagosome formation in the cell in order to address those questions on autophagosome formation. The semi-synthetic LC3 proteins are expected to confer a temporal control and to realize manipulation of protein structure, which renders such studies possible. Second, I intend to develop a versatile approach targeting specific endogenous proteins using a reversible chemically induced dimerization (CID) system, termed as “knock on and off” strategy. I plan to use this approach to elucidate the function of two distinct PI3K complexes in autophagosome formation. On one hand, the establishment of novel approaches will open up a new avenue for studying biological processes. On the other hand, the use of the tool will reveal the mechanism of autophagy.
Summary
The interest on autophagy, an evolutionarily conserved process in eukaryotes, has enormously increased in the last years, since autophagy is involved in many diseases such as cancer and neurodegenerative disorders. Autophagosome formation is the key process in autophagy. Despite extensive work, the model of autophagosome formation is not yet well established. Some important questions on autophagosome biogenesis remain to be elusive, such as where the bona fide marker protein of autophagosome, LC3, is lipidated, how lipidated LC3 functions in autophagosome formation, and how the proteins for LC3 lipidation and delipidation are involved in autophagosome formation. Although genetic approaches have been useful to identify genes involved in autophagy, they are chronic and thereby the dynamics of phenotypic change cannot be followed, making them not suited for study highly dynamic process such as autophagosome formation. Herein, I propose to develop and use novel chemical probes to address these issues. First, I plan to prepare semi-synthetic caged LC3 proteins and apply them to monitor dynamics of autophagosome formation in the cell in order to address those questions on autophagosome formation. The semi-synthetic LC3 proteins are expected to confer a temporal control and to realize manipulation of protein structure, which renders such studies possible. Second, I intend to develop a versatile approach targeting specific endogenous proteins using a reversible chemically induced dimerization (CID) system, termed as “knock on and off” strategy. I plan to use this approach to elucidate the function of two distinct PI3K complexes in autophagosome formation. On one hand, the establishment of novel approaches will open up a new avenue for studying biological processes. On the other hand, the use of the tool will reveal the mechanism of autophagy.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym COMPASS
Project Control for Orbit Manoeuvring through Perturbations for Application to Space Systems
Researcher (PI) Camilla Colombo
Host Institution (HI) POLITECNICO DI MILANO
Country Italy
Call Details Starting Grant (StG), PE8, ERC-2015-STG
Summary Space benefits mankind through the services it provides to Earth. Future space activities progress thanks to space transfer and are safeguarded by space situation awareness. Natural orbit perturbations are responsible for the trajectory divergence from the nominal two-body problem, increasing the requirements for orbit control; whereas, in space situation awareness, they influence the orbit evolution of space debris that could cause hazard to operational spacecraft and near Earth objects that may intersect the Earth. However, this project proposes to leverage the dynamics of natural orbit perturbations to significantly reduce current extreme high mission cost and create new opportunities for space exploration and exploitation.
The COMPASS project will bridge over the disciplines of orbital dynamics, dynamical systems theory, optimisation and space mission design by developing novel techniques for orbit manoeuvring by “surfing” through orbit perturbations. The use of semi-analytical techniques and tools of dynamical systems theory will lay the foundation for a new understanding of the dynamics of orbit perturbations. We will develop an optimiser that progressively explores the phase space and, though spacecraft parameters and propulsion manoeuvres, governs the effect of perturbations to reach the desired orbit. It is the ambition of COMPASS to radically change the current space mission design philosophy: from counteracting disturbances, to exploiting natural and artificial perturbations.
COMPASS will benefit from the extensive international network of the PI, including the ESA, NASA, JAXA, CNES, and the UK space agency. Indeed, the proposed idea of optimal navigation through orbit perturbations will address various major engineering challenges in space situation awareness, for application to space debris evolution and mitigation, missions to asteroids for their detection, exploration and deflection, and in space transfers, for perturbation-enhanced trajectory design.
Summary
Space benefits mankind through the services it provides to Earth. Future space activities progress thanks to space transfer and are safeguarded by space situation awareness. Natural orbit perturbations are responsible for the trajectory divergence from the nominal two-body problem, increasing the requirements for orbit control; whereas, in space situation awareness, they influence the orbit evolution of space debris that could cause hazard to operational spacecraft and near Earth objects that may intersect the Earth. However, this project proposes to leverage the dynamics of natural orbit perturbations to significantly reduce current extreme high mission cost and create new opportunities for space exploration and exploitation.
The COMPASS project will bridge over the disciplines of orbital dynamics, dynamical systems theory, optimisation and space mission design by developing novel techniques for orbit manoeuvring by “surfing” through orbit perturbations. The use of semi-analytical techniques and tools of dynamical systems theory will lay the foundation for a new understanding of the dynamics of orbit perturbations. We will develop an optimiser that progressively explores the phase space and, though spacecraft parameters and propulsion manoeuvres, governs the effect of perturbations to reach the desired orbit. It is the ambition of COMPASS to radically change the current space mission design philosophy: from counteracting disturbances, to exploiting natural and artificial perturbations.
COMPASS will benefit from the extensive international network of the PI, including the ESA, NASA, JAXA, CNES, and the UK space agency. Indeed, the proposed idea of optimal navigation through orbit perturbations will address various major engineering challenges in space situation awareness, for application to space debris evolution and mitigation, missions to asteroids for their detection, exploration and deflection, and in space transfers, for perturbation-enhanced trajectory design.
Max ERC Funding
1 499 021 €
Duration
Start date: 2016-08-01, End date: 2021-07-31
Project acronym ComplexSwimmers
Project Biocompatible and Interactive Artificial Micro- and Nanoswimmers and Their Applications
Researcher (PI) Giovanni Volpe
Host Institution (HI) GOETEBORGS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE4, ERC-2015-STG
Summary Microswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equilibrium physics underlying the adaptive and collective behavior of biological entities such as chemotactic bacteria and eukaryotic cells. From the more applied side, they provide tantalizing options to perform tasks not easily achievable with other available techniques, such as the targeted localization, pick-up and delivery of microscopic and nanoscopic cargoes, e.g., in drug delivery, bioremediation and chemical sensing.
However, there are still several open challenges that need to be tackled in order to achieve the full scientific and technological potential of microswimmers in real-life settings. The main challenges are: (1) to identify a biocompatible propulstion mechanism and energy supply capable of lasting for the whole particle life-cycle; (2) to understand their behavior in complex and crowded environments; (3) to learn how to engineer emergent behaviors; and (4) to scale down their dimensions towards the nanoscale.
This project aims at tackling these challenges by developing biocompatible microswimmers capable of elaborate behaviors, by engineering their performance when interacting with other particles and with a complex environment, and by developing working nanoswimmers.
To achieve these goals, we have laid out a roadmap that will lead us to push the frontiers of the current understanding of active matter both at the mesoscopic and at the nanoscopic scale, and will permit us to develop some technologically disruptive techniques, namely, targeted delivery of cargoes within complex environments, which is of interest for drug delivery and bioremediation, and efficient sorting of chiral nanoparticles, which is of interest for biomedical and pharmaceutical applications.
Summary
Microswimmers, i.e., biological and artificial microscopic objects capable of self-propulsion, have been attracting a growing interest from the biological and physical communities. From the fundamental side, their study can shed light on the far-from-equilibrium physics underlying the adaptive and collective behavior of biological entities such as chemotactic bacteria and eukaryotic cells. From the more applied side, they provide tantalizing options to perform tasks not easily achievable with other available techniques, such as the targeted localization, pick-up and delivery of microscopic and nanoscopic cargoes, e.g., in drug delivery, bioremediation and chemical sensing.
However, there are still several open challenges that need to be tackled in order to achieve the full scientific and technological potential of microswimmers in real-life settings. The main challenges are: (1) to identify a biocompatible propulstion mechanism and energy supply capable of lasting for the whole particle life-cycle; (2) to understand their behavior in complex and crowded environments; (3) to learn how to engineer emergent behaviors; and (4) to scale down their dimensions towards the nanoscale.
This project aims at tackling these challenges by developing biocompatible microswimmers capable of elaborate behaviors, by engineering their performance when interacting with other particles and with a complex environment, and by developing working nanoswimmers.
To achieve these goals, we have laid out a roadmap that will lead us to push the frontiers of the current understanding of active matter both at the mesoscopic and at the nanoscopic scale, and will permit us to develop some technologically disruptive techniques, namely, targeted delivery of cargoes within complex environments, which is of interest for drug delivery and bioremediation, and efficient sorting of chiral nanoparticles, which is of interest for biomedical and pharmaceutical applications.
Max ERC Funding
1 497 500 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym DARKJETS
Project Discovery strategies for Dark Matter and new phenomena in hadronic signatures with the ATLAS detector at the Large Hadron Collider
Researcher (PI) Caterina Doglioni
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), PE2, ERC-2015-STG
Summary The Standard Model of Particle Physics describes the fundamental components of ordinary matter and their interactions. Despite its success in predicting many experimental results, the Standard Model fails to account for a number of interesting phenomena. One phenomenon of particular interest is the large excess of unobservable (Dark) matter in the Universe. This excess cannot be explained by Standard Model particles. A compelling hypothesis is that Dark Matter is comprised of particles that can be produced in the proton-proton collisions from the Large Hadron Collider (LHC) at CERN.
Within this project, I will build a team of researchers at Lund University dedicated to searches for signals of the presence of Dark Matter particles. The discovery strategies employed seek the decays of particles that either mediate the interactions between Dark and Standard Model particles or are produced in association with Dark Matter. These new particles manifest in detectors as two, three, or four collimated jets of particles (hadronic jets).
The LHC will resume delivery of proton-proton collisions to the ATLAS detector in 2015. Searches for new, rare, low mass particles such as Dark Matter mediators have so far been hindered by constraints on the rates of data that can be stored. These constraints will be overcome through the implementation of a novel real-time data analysis technique and a new search signature, both introduced to ATLAS by this project. The coincidence of this project with the upcoming LHC runs and the software and hardware improvements within the ATLAS detector is a unique opportunity to increase the sensitivity to hadronically decaying new particles by a large margin with respect to any previous searches. The results of these searches will be interpreted within a comprehensive and coherent set of theoretical benchmarks, highlighting the strengths of collider experiments in the global quest for Dark Matter.
Summary
The Standard Model of Particle Physics describes the fundamental components of ordinary matter and their interactions. Despite its success in predicting many experimental results, the Standard Model fails to account for a number of interesting phenomena. One phenomenon of particular interest is the large excess of unobservable (Dark) matter in the Universe. This excess cannot be explained by Standard Model particles. A compelling hypothesis is that Dark Matter is comprised of particles that can be produced in the proton-proton collisions from the Large Hadron Collider (LHC) at CERN.
Within this project, I will build a team of researchers at Lund University dedicated to searches for signals of the presence of Dark Matter particles. The discovery strategies employed seek the decays of particles that either mediate the interactions between Dark and Standard Model particles or are produced in association with Dark Matter. These new particles manifest in detectors as two, three, or four collimated jets of particles (hadronic jets).
The LHC will resume delivery of proton-proton collisions to the ATLAS detector in 2015. Searches for new, rare, low mass particles such as Dark Matter mediators have so far been hindered by constraints on the rates of data that can be stored. These constraints will be overcome through the implementation of a novel real-time data analysis technique and a new search signature, both introduced to ATLAS by this project. The coincidence of this project with the upcoming LHC runs and the software and hardware improvements within the ATLAS detector is a unique opportunity to increase the sensitivity to hadronically decaying new particles by a large margin with respect to any previous searches. The results of these searches will be interpreted within a comprehensive and coherent set of theoretical benchmarks, highlighting the strengths of collider experiments in the global quest for Dark Matter.
Max ERC Funding
1 268 076 €
Duration
Start date: 2016-02-01, End date: 2021-07-31
Project acronym DIALOY
Project Mosaic loss of chromosome Y (LOY) in blood cells - a new biomarker for risk of cancer and Alzheimer’s disease in men
Researcher (PI) Lars Anders Forsberg
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Starting Grant (StG), LS7, ERC-2015-STG
Summary My recent discoveries show that mosaic loss of chromosome Y (LOY) in peripheral blood is associated with increased risks of cancer and Alzheimer’s disease (AD). These conditions are responsible for >50% of morbidity/mortality in aging men. More than 15% of men older than 70 show some degree of LOY and these men survive on average only half as long as men without LOY. Smoking is strongly associated with LOY and remarkably, the fraction of cells with LOY decreases after cessation of smoking. Cells with LOY can be detected, and disease risks predicted, many years before clinical manifestation of disease. These results of associations between LOY, cancer and smoking have been published in Nature Genetics and Science during 2014.
The overall objective of the proposal is to develop LOY as a new, strong and predictive biomarker. To this end, the research program focuses on three objectives: 1) expanding the study of LOY and associations with disease risks in still larger cohorts; 2) investigating functional aspects of LOY; and 3) develop improved technology for LOY-detection. The successful execution of the project is essential before LOY-testing in clinics can be realized.
Diagnosis of cancer and AD in modern medicine is based on clinical symptoms of disease. Through earlier identification of individuals at increased risk for disease, preventive strategies could be applied, before the severe stages appear. Preliminary results affirm the feasibility of the project and provide proof-of-concept that LOY-tests can be used for early identification of men with increased risks for these diseases. In addition to improving diagnostics and therapeutics; implementation of LOY-testing could prevent smoking-related disease and reduce the health care costs. In the end, LOY-testing could decrease male mortality rates and possibly eliminate the sex-difference in life expectancy. The project will therefore benefit individual patients as well as healthcare systems and society at large.
Summary
My recent discoveries show that mosaic loss of chromosome Y (LOY) in peripheral blood is associated with increased risks of cancer and Alzheimer’s disease (AD). These conditions are responsible for >50% of morbidity/mortality in aging men. More than 15% of men older than 70 show some degree of LOY and these men survive on average only half as long as men without LOY. Smoking is strongly associated with LOY and remarkably, the fraction of cells with LOY decreases after cessation of smoking. Cells with LOY can be detected, and disease risks predicted, many years before clinical manifestation of disease. These results of associations between LOY, cancer and smoking have been published in Nature Genetics and Science during 2014.
The overall objective of the proposal is to develop LOY as a new, strong and predictive biomarker. To this end, the research program focuses on three objectives: 1) expanding the study of LOY and associations with disease risks in still larger cohorts; 2) investigating functional aspects of LOY; and 3) develop improved technology for LOY-detection. The successful execution of the project is essential before LOY-testing in clinics can be realized.
Diagnosis of cancer and AD in modern medicine is based on clinical symptoms of disease. Through earlier identification of individuals at increased risk for disease, preventive strategies could be applied, before the severe stages appear. Preliminary results affirm the feasibility of the project and provide proof-of-concept that LOY-tests can be used for early identification of men with increased risks for these diseases. In addition to improving diagnostics and therapeutics; implementation of LOY-testing could prevent smoking-related disease and reduce the health care costs. In the end, LOY-testing could decrease male mortality rates and possibly eliminate the sex-difference in life expectancy. The project will therefore benefit individual patients as well as healthcare systems and society at large.
Max ERC Funding
1 525 000 €
Duration
Start date: 2016-03-01, End date: 2021-02-28
Project acronym DMAP
Project Data Mining Algorithms in Practice
Researcher (PI) Flavio Chierichetti
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Country Italy
Call Details Starting Grant (StG), PE6, ERC-2015-STG
Summary Data Mining algorithms are a cornerstone of today's Internet-related services and products. We aim to tackle some of the most important problems in Data Mining --- our goal is to develop a systematic theoretical understanding of certain simple algorithms that, in spite of being at the core of today's web industry, are not yet well understood in terms of their properties and performances, and to develop new simple algorithms for fundamental problems in this domain that have so far escaped a satisfactory solution.
Summary
Data Mining algorithms are a cornerstone of today's Internet-related services and products. We aim to tackle some of the most important problems in Data Mining --- our goal is to develop a systematic theoretical understanding of certain simple algorithms that, in spite of being at the core of today's web industry, are not yet well understood in terms of their properties and performances, and to develop new simple algorithms for fundamental problems in this domain that have so far escaped a satisfactory solution.
Max ERC Funding
1 137 500 €
Duration
Start date: 2016-02-01, End date: 2021-01-31
Project acronym DYNAP
Project Dynamic Penetrating Peptide Adaptamers
Researcher (PI) Javier Montenegro Garcia
Host Institution (HI) UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Country Spain
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary The aim of this proposal is to identify, at the molecular level, the minimal topological and structural motifs that govern the membrane translocation of short peptides. A covalent reversible bond strategy will be developed for the synthesis of self-adaptive penetrating peptides (adaptamers) for targeted delivery.
It is known that the recently developed therapeutic technologies (i.e. gene therapy, chemotherapy, hyperthermia, etc.) cannot reach their expected potential due to limitations in the current delivery strategies, which hinder the efficient targeting of the appropriate tissues, cells and organelles. Despite the enormous therapeutic potential of short penetrating peptides, these molecules suffer from drawbacks such as toxicity, instability to protease digestion and lack of specificity.
Dynamic covalent chemistry has significant synthetic advantages. In the proposed research, peptide scaffolds with clickable reversible groups (e.g. hydrazide) will be conjugated with collections of aldehydes to afford self-adaptive biomimetic transporters, whose secondary structure and penetrating properties will be systematically characterized by biophysical, cell-biology and pattern recognition techniques.
The versatility of dynamic supramolecular “peptide adaptamers” with precisely positioned protein ligands will be explored for multivalent specific recognition, protein transport, cell targeting of drugs and probes and membrane epitoping.
Additionally, we propose to synthesise dynamic and environmentally sensitive fluorescent probes for biocompatible membrane labelling and uptake signalling.
The resulting discoveries of this research will allow the formulation of novel transfecting reagents for gene therapy, selective platforms for drug-delivery and the development of dynamic fluorescent membrane probes. The potential results of this proposal will shake the fields of drug-delivery and non-viral gene transfection and will resolve the limitations of the current approaches.
Summary
The aim of this proposal is to identify, at the molecular level, the minimal topological and structural motifs that govern the membrane translocation of short peptides. A covalent reversible bond strategy will be developed for the synthesis of self-adaptive penetrating peptides (adaptamers) for targeted delivery.
It is known that the recently developed therapeutic technologies (i.e. gene therapy, chemotherapy, hyperthermia, etc.) cannot reach their expected potential due to limitations in the current delivery strategies, which hinder the efficient targeting of the appropriate tissues, cells and organelles. Despite the enormous therapeutic potential of short penetrating peptides, these molecules suffer from drawbacks such as toxicity, instability to protease digestion and lack of specificity.
Dynamic covalent chemistry has significant synthetic advantages. In the proposed research, peptide scaffolds with clickable reversible groups (e.g. hydrazide) will be conjugated with collections of aldehydes to afford self-adaptive biomimetic transporters, whose secondary structure and penetrating properties will be systematically characterized by biophysical, cell-biology and pattern recognition techniques.
The versatility of dynamic supramolecular “peptide adaptamers” with precisely positioned protein ligands will be explored for multivalent specific recognition, protein transport, cell targeting of drugs and probes and membrane epitoping.
Additionally, we propose to synthesise dynamic and environmentally sensitive fluorescent probes for biocompatible membrane labelling and uptake signalling.
The resulting discoveries of this research will allow the formulation of novel transfecting reagents for gene therapy, selective platforms for drug-delivery and the development of dynamic fluorescent membrane probes. The potential results of this proposal will shake the fields of drug-delivery and non-viral gene transfection and will resolve the limitations of the current approaches.
Max ERC Funding
1 492 525 €
Duration
Start date: 2016-02-01, End date: 2022-07-31
