Project acronym BONDS
Project Bilayered ON-Demand Scaffolds: On-Demand Delivery from induced Pluripotent Stem Cell Derived Scaffolds for Diabetic Foot Ulcers
Researcher (PI) Cathal KEARNEY
Host Institution (HI) ROYAL COLLEGE OF SURGEONS IN IRELAND
Country Ireland
Call Details Starting Grant (StG), PE8, ERC-2017-STG
Summary This program’s goal is to develop a scaffold using a new biomaterial source that is functionalised with on-demand delivery of genes for coordinated healing of diabetic foot ulcers (DFUs). DFUs are chronic wounds that are often recalcitrant to treatment, which devastatingly results in lower leg amputation. This project builds on the PI’s experience growing matrix from induced-pluripotent stem cell derived (iPS)-fibroblasts and in developing on-demand drug delivery technologies. The aim of this project is to first develop a SiPS: a scaffold from iPS-fibroblast grown matrix, which has never been tested as a source material for scaffolds. iPS-fibroblasts grow a more pro-repair and angiogenic matrix than (non-iPS) adult fibroblasts. The SiPS structure will be bilayered to mimic native skin: dermis made mostly by fibroblasts and epidermis made by keratinocytes. The dermal layer will consist of a porous scaffold with optimised pore size and mechanical properties and the epidermal layer will be film-like, optimised for keratinisation.
Second, the SiPS will be functionalised with delivery of plasmid-DNA (platelet derived growth factor gene, pPDGF) to direct angiogenesis on-demand. As DFUs undergo uncoordinated healing, timed pPDGF delivery will guide them through angiogenesis and healing. To achieve this, alginate microparticles, designed to respond to ultrasound by releasing pPDGF, will be interspersed throughout the SiPS. This BONDS will be tested in an in vivo pre-clinical DFU model to confirm its ability to heal wounds by providing cells with the appropriate biomimetic scaffold environment and timed directions for healing. With >100 million current diabetics expected to get a DFU, the BONDS would have a powerful clinical impact.
This research program combines a disruptive technology, the SiPS, with a new platform for on-demand delivery of pDNA to heal DFUs. The PI will build his lab around these innovative platforms, adapting them for treatment of diverse complex wounds.
Summary
This program’s goal is to develop a scaffold using a new biomaterial source that is functionalised with on-demand delivery of genes for coordinated healing of diabetic foot ulcers (DFUs). DFUs are chronic wounds that are often recalcitrant to treatment, which devastatingly results in lower leg amputation. This project builds on the PI’s experience growing matrix from induced-pluripotent stem cell derived (iPS)-fibroblasts and in developing on-demand drug delivery technologies. The aim of this project is to first develop a SiPS: a scaffold from iPS-fibroblast grown matrix, which has never been tested as a source material for scaffolds. iPS-fibroblasts grow a more pro-repair and angiogenic matrix than (non-iPS) adult fibroblasts. The SiPS structure will be bilayered to mimic native skin: dermis made mostly by fibroblasts and epidermis made by keratinocytes. The dermal layer will consist of a porous scaffold with optimised pore size and mechanical properties and the epidermal layer will be film-like, optimised for keratinisation.
Second, the SiPS will be functionalised with delivery of plasmid-DNA (platelet derived growth factor gene, pPDGF) to direct angiogenesis on-demand. As DFUs undergo uncoordinated healing, timed pPDGF delivery will guide them through angiogenesis and healing. To achieve this, alginate microparticles, designed to respond to ultrasound by releasing pPDGF, will be interspersed throughout the SiPS. This BONDS will be tested in an in vivo pre-clinical DFU model to confirm its ability to heal wounds by providing cells with the appropriate biomimetic scaffold environment and timed directions for healing. With >100 million current diabetics expected to get a DFU, the BONDS would have a powerful clinical impact.
This research program combines a disruptive technology, the SiPS, with a new platform for on-demand delivery of pDNA to heal DFUs. The PI will build his lab around these innovative platforms, adapting them for treatment of diverse complex wounds.
Max ERC Funding
1 372 135 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym ODYSSEY
Project Open dynamics of interacting and disordered quantum systems
Researcher (PI) John GOOLD
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Country Ireland
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary This research proposal focuses on the open quantum system dynamics of disordered and interacting many- body systems coupled to external baths. The dynamics of systems which contain both disorder and interactions are currently under intense theoretical investigation in condensed matter physics due to the discovery of a new phase of matter known as many-body localization. With the experimental realization of such systems in mind, this proposal addresses an essential issue which is to understand how coupling to external degrees of freedom influences dynamics. These systems are intrinsically complex and lie beyond the unitary closed system paradigm, so the research proposed here contains interdisciplinary methodology beyond the mainstream in condensed matter physics ranging from quantum information to quantum optics. The project has three principal objectives each of which would represent a major contribution to the field:
O1. To describe the dynamics of a interacting, disordered many-body systems when coupled to external baths.
O2. To perform a full characterization of spin and energy transport in their non-equilibrium steady state.
O3. To explore the system capabilities as steady state thermal machine from a systematic microscopic perspective.
This will be the first comprehensive study of the open system phenomenology of disordered interacting many-body
systems. It will also allow for the systematic study of energy and spin transport and the exploration of the potential of these systems as steady state thermal machines. In order to successfully carry out the work proposed here, the applicant will build a world class team at Trinity College Dublin. Due to his track record and interdisciplinary background in many-body physics, quantum information and statistical mechanics combined with his personal drive and ambition the applicant is in a formidable position to successfully undertake this task with the platform provided by this ERC Starting Grant.
Summary
This research proposal focuses on the open quantum system dynamics of disordered and interacting many- body systems coupled to external baths. The dynamics of systems which contain both disorder and interactions are currently under intense theoretical investigation in condensed matter physics due to the discovery of a new phase of matter known as many-body localization. With the experimental realization of such systems in mind, this proposal addresses an essential issue which is to understand how coupling to external degrees of freedom influences dynamics. These systems are intrinsically complex and lie beyond the unitary closed system paradigm, so the research proposed here contains interdisciplinary methodology beyond the mainstream in condensed matter physics ranging from quantum information to quantum optics. The project has three principal objectives each of which would represent a major contribution to the field:
O1. To describe the dynamics of a interacting, disordered many-body systems when coupled to external baths.
O2. To perform a full characterization of spin and energy transport in their non-equilibrium steady state.
O3. To explore the system capabilities as steady state thermal machine from a systematic microscopic perspective.
This will be the first comprehensive study of the open system phenomenology of disordered interacting many-body
systems. It will also allow for the systematic study of energy and spin transport and the exploration of the potential of these systems as steady state thermal machines. In order to successfully carry out the work proposed here, the applicant will build a world class team at Trinity College Dublin. Due to his track record and interdisciplinary background in many-body physics, quantum information and statistical mechanics combined with his personal drive and ambition the applicant is in a formidable position to successfully undertake this task with the platform provided by this ERC Starting Grant.
Max ERC Funding
1 333 325 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym REACT
Project REsponsive theranostic nanosystems for Advanced Cancer Treatment
Researcher (PI) Eduardo RUIZ-HERNANDEZ
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Country Ireland
Call Details Starting Grant (StG), PE8, ERC-2017-STG
Summary REACT aims to dramatically impact the targeted release of diagnostic agents and drugs with nanomedicines that respond to biological cues or changing pathophysiological conditions, thus enabling ultrasensitive diagnosis and exquisite therapy selectivity. Nanomedicine research against cancer focuses on the local targeted delivery of chemotherapeutics to enhance drug efficacy and reduce side effects. Despite all the efforts in the design of chemotherapeutic agents as nanomedicines, hardly any improvement has been translated into benefits for patients’ survival. There is an urgent need for improved carrier systems able to deliver high doses of diagnostic agents and anti-cancer drugs to the tumor. Stimuli responsive carriers are promising candidates since the release of the cargo can be triggered locally in the tumor environment. Currently, there exists an unparalleled effort to identify genes, proteins and metabolites implicated in human disease and utilize systems biology and mathematical approaches in order to develop new prognostic tools for the treatment of cancer and develop more targeted therapies for patients. As an expert in drug delivery systems, the PI intends to bring all these efforts and advances into the design of stimuli responsive organic-inorganic hybrid nanoparticles that can adapt their response to the biological milieu. The novel engineered delivery systems will consist of an inorganic porous matrix surface-modified with tumor-specific molecules with the ability to sense changes in the environmental conditions and react by providing a proportional release. These nanosystems can potentially be employed for early in vitro diagnosis through effective screening of deadly tumors, such as neuroblastoma and glioblastoma. Moreover, through the sustained delivery of the nanosystems from injectable gels that can be locally implanted in patients at risk of developing a tumor, a clinically relevant tool for in vivo diagnosis and targeted therapy can be achieved.
Summary
REACT aims to dramatically impact the targeted release of diagnostic agents and drugs with nanomedicines that respond to biological cues or changing pathophysiological conditions, thus enabling ultrasensitive diagnosis and exquisite therapy selectivity. Nanomedicine research against cancer focuses on the local targeted delivery of chemotherapeutics to enhance drug efficacy and reduce side effects. Despite all the efforts in the design of chemotherapeutic agents as nanomedicines, hardly any improvement has been translated into benefits for patients’ survival. There is an urgent need for improved carrier systems able to deliver high doses of diagnostic agents and anti-cancer drugs to the tumor. Stimuli responsive carriers are promising candidates since the release of the cargo can be triggered locally in the tumor environment. Currently, there exists an unparalleled effort to identify genes, proteins and metabolites implicated in human disease and utilize systems biology and mathematical approaches in order to develop new prognostic tools for the treatment of cancer and develop more targeted therapies for patients. As an expert in drug delivery systems, the PI intends to bring all these efforts and advances into the design of stimuli responsive organic-inorganic hybrid nanoparticles that can adapt their response to the biological milieu. The novel engineered delivery systems will consist of an inorganic porous matrix surface-modified with tumor-specific molecules with the ability to sense changes in the environmental conditions and react by providing a proportional release. These nanosystems can potentially be employed for early in vitro diagnosis through effective screening of deadly tumors, such as neuroblastoma and glioblastoma. Moreover, through the sustained delivery of the nanosystems from injectable gels that can be locally implanted in patients at risk of developing a tumor, a clinically relevant tool for in vivo diagnosis and targeted therapy can be achieved.
Max ERC Funding
1 498 346 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym SUPERSTARS
Project Type Ia supernovae: from explosions to cosmology
Researcher (PI) Kate MAGUIRE
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Country Ireland
Call Details Starting Grant (StG), PE9, ERC-2017-STG
Summary Type Ia supernovae (SNe Ia) are the incredibly luminous deaths of white dwarfs in binaries. They play a vital role in chemical enrichment, galaxy feedback, stellar evolution, and were instrumental in the discovery of dark energy. However, what are the progenitor systems of SNe Ia, and how they explode remains a mystery. My recent work has concluded the controversial result that there may be more than one way to produce SNe Ia. As SN Ia cosmology samples reach higher precision, understanding subtle differences in their properties becomes increasingly important. A surprising diversity in white-dwarf explosions has also been uncovered, with a much wider-than-expected range in luminosities, light-curve timescales and spectral properties. A key open question is ‘What explosion mechanisms result in normal SNe Ia compared to more exotic transients?’
My team will use novel early-time observations (within hours of explosion) of 100 SNe Ia in a volume-limited search (<75 Mpc). The targets will come from the ATLAS and Pan-STARRS surveys that will provide unprecedented sky coverage and cadence (>20000 square degrees, up to four times a night). These data will be combined with key progenitor diagnostics of each SN (companion interaction, circumstellar material, central density studies). The observed zoo of transients predicted to result from white-dwarf explosions (He-shell explosions, tidal-disruption events, violent mergers) will also be investigated, with the goal of constraining the mechanisms by which white dwarfs can explode. My access to ATLAS/Pan-STARRS and my previous experience puts me in a unique position to obtain ‘day-zero’ light curves, rapid spectroscopic follow-up, and late-time observations. The data will be analysed with detailed spectral modelling to unveil the progenitors and diversity of SNe Ia. This project is timely with the potential for significant breakthroughs to be made before the start of the next-generation ‘transient machine’, LSST in ~2021.
Summary
Type Ia supernovae (SNe Ia) are the incredibly luminous deaths of white dwarfs in binaries. They play a vital role in chemical enrichment, galaxy feedback, stellar evolution, and were instrumental in the discovery of dark energy. However, what are the progenitor systems of SNe Ia, and how they explode remains a mystery. My recent work has concluded the controversial result that there may be more than one way to produce SNe Ia. As SN Ia cosmology samples reach higher precision, understanding subtle differences in their properties becomes increasingly important. A surprising diversity in white-dwarf explosions has also been uncovered, with a much wider-than-expected range in luminosities, light-curve timescales and spectral properties. A key open question is ‘What explosion mechanisms result in normal SNe Ia compared to more exotic transients?’
My team will use novel early-time observations (within hours of explosion) of 100 SNe Ia in a volume-limited search (<75 Mpc). The targets will come from the ATLAS and Pan-STARRS surveys that will provide unprecedented sky coverage and cadence (>20000 square degrees, up to four times a night). These data will be combined with key progenitor diagnostics of each SN (companion interaction, circumstellar material, central density studies). The observed zoo of transients predicted to result from white-dwarf explosions (He-shell explosions, tidal-disruption events, violent mergers) will also be investigated, with the goal of constraining the mechanisms by which white dwarfs can explode. My access to ATLAS/Pan-STARRS and my previous experience puts me in a unique position to obtain ‘day-zero’ light curves, rapid spectroscopic follow-up, and late-time observations. The data will be analysed with detailed spectral modelling to unveil the progenitors and diversity of SNe Ia. This project is timely with the potential for significant breakthroughs to be made before the start of the next-generation ‘transient machine’, LSST in ~2021.
Max ERC Funding
1 876 496 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
