Project acronym EDIP
Project Evolution of Development In Plants
Researcher (PI) Jane Alison Langdale
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), LS3, ERC-2008-AdG
Summary Different morphologies evolve in different organisms in response to changing environments. As land plants evolved, developmental mechanisms were either generated de novo, or were recruited from existing toolkits and adapted to facilitate changes in form. Some of these changes occurred once, others on multiple occasions, and others were gained and then subsequently lost in a subset of lineages. Why have certain forms survived and others not? Why does a fern look different from a flowering plant, and why should developmental biologists care? By determining how many different ways there are to generate a particular morphology, we gain an understanding of whether a particular transition is constrained. This basic information allows an assessment of the extent to which genetic variation can modify developmental mechanisms and an indication of the degree of developmental plasticity that is possible and/or tolerated both within and between species. This proposal aims to characterize the developmental mechanisms that underpin the diverse shoot forms seen in extant plant species. The main goal is to compare developmental mechanisms that operate in vegetative shoots of bryophytes, lycophytes, ferns and angiosperms, with a view to understanding the constraints that limit morphological variation. Specifically, we will investigate the developmental basis of three major innovations that altered the morphology of vegetative shoots during land plant evolution: 1) formation of a multi-cellular embryo; 2) organization of apical growth centres and 3) patterning of leaves in distinct spatial arrangements along the shoot. To facilitate progress we also aim to develop transgenic methods, create mutant populations and generate digital transcriptomes for model species at key phylogenetic nodes. The proposed work will generate scenarios to explain how land plant form evolved and perhaps more importantly, how it could change in the future.
Summary
Different morphologies evolve in different organisms in response to changing environments. As land plants evolved, developmental mechanisms were either generated de novo, or were recruited from existing toolkits and adapted to facilitate changes in form. Some of these changes occurred once, others on multiple occasions, and others were gained and then subsequently lost in a subset of lineages. Why have certain forms survived and others not? Why does a fern look different from a flowering plant, and why should developmental biologists care? By determining how many different ways there are to generate a particular morphology, we gain an understanding of whether a particular transition is constrained. This basic information allows an assessment of the extent to which genetic variation can modify developmental mechanisms and an indication of the degree of developmental plasticity that is possible and/or tolerated both within and between species. This proposal aims to characterize the developmental mechanisms that underpin the diverse shoot forms seen in extant plant species. The main goal is to compare developmental mechanisms that operate in vegetative shoots of bryophytes, lycophytes, ferns and angiosperms, with a view to understanding the constraints that limit morphological variation. Specifically, we will investigate the developmental basis of three major innovations that altered the morphology of vegetative shoots during land plant evolution: 1) formation of a multi-cellular embryo; 2) organization of apical growth centres and 3) patterning of leaves in distinct spatial arrangements along the shoot. To facilitate progress we also aim to develop transgenic methods, create mutant populations and generate digital transcriptomes for model species at key phylogenetic nodes. The proposed work will generate scenarios to explain how land plant form evolved and perhaps more importantly, how it could change in the future.
Max ERC Funding
2 230 732 €
Duration
Start date: 2009-07-01, End date: 2015-06-30
Project acronym MAMMASTEM
Project Molecular mechanisms of the regulation of mammary stem cell homeostasis and their subversion in cancer
Researcher (PI) Pier Paolo Di Fiore
Host Institution (HI) IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE
Call Details Advanced Grant (AdG), LS3, ERC-2008-AdG
Summary Stem cells (SCs) are thought to be integral to the development and progression of cancer, and their eradication may be essential for the cure of cancer. Yet, direct proof is lacking due to our poor understanding of the molecular differences between normal and cancer SCs. We will investigate normal and cancer mammary stem cells (MSCs) by focusing on the role of the cell fate determinant Numb in two signaling axes: Numb:Notch and Numb:p53. Numb is a tumor suppressor in human breast cancer. Its expression is lost, through increased degradation, in ~50% of breast cancers. These Numbneg cancers display overall poorer prognosis. Mechanistically, loss of Numb causes increased Notch signaling and decreased p53 signaling. Thus, Numb controls both an oncogenic pathway (the Numb:Notch axis) and a tumor suppressor one (the Numb:p53 axis). We showed that Numb is asymmetrically partitioned at the first division of normal MSCs and hypothesize that loss of Numb affects the kinetics of division and MSC fate. Our specific aims are to: 1. Define the role of the Numb:Notch and Numb:p53 axes in normal and cancer MSCs. We will exploit our capacity to propagate and isolate MSCs to near-purity, for biological, biochemical and omics approaches. In this task, we will integrate knowledge derived from the analysis of real human cancers and of genetically-defined mouse models. 2. Define the broader biological context of Numb impact in stem cell biology, by analyzing the role of endocytosis in MSC fate determination. This is justified by the fact that Numb is an endocytic protein and that data in Drosophila indicate a complex role of endocytosis in cell fate specification. 3. Identify the E3 ligase responsible for Numb degradation in Numbneg breast tumors, in order to obtain druggable targets to restore Numb levels in these tumors. If successful, our work will elucidate major mechanisms of normal and cancer stem cell regulation, and provide tools for SC-specific therapeutic intervention.
Summary
Stem cells (SCs) are thought to be integral to the development and progression of cancer, and their eradication may be essential for the cure of cancer. Yet, direct proof is lacking due to our poor understanding of the molecular differences between normal and cancer SCs. We will investigate normal and cancer mammary stem cells (MSCs) by focusing on the role of the cell fate determinant Numb in two signaling axes: Numb:Notch and Numb:p53. Numb is a tumor suppressor in human breast cancer. Its expression is lost, through increased degradation, in ~50% of breast cancers. These Numbneg cancers display overall poorer prognosis. Mechanistically, loss of Numb causes increased Notch signaling and decreased p53 signaling. Thus, Numb controls both an oncogenic pathway (the Numb:Notch axis) and a tumor suppressor one (the Numb:p53 axis). We showed that Numb is asymmetrically partitioned at the first division of normal MSCs and hypothesize that loss of Numb affects the kinetics of division and MSC fate. Our specific aims are to: 1. Define the role of the Numb:Notch and Numb:p53 axes in normal and cancer MSCs. We will exploit our capacity to propagate and isolate MSCs to near-purity, for biological, biochemical and omics approaches. In this task, we will integrate knowledge derived from the analysis of real human cancers and of genetically-defined mouse models. 2. Define the broader biological context of Numb impact in stem cell biology, by analyzing the role of endocytosis in MSC fate determination. This is justified by the fact that Numb is an endocytic protein and that data in Drosophila indicate a complex role of endocytosis in cell fate specification. 3. Identify the E3 ligase responsible for Numb degradation in Numbneg breast tumors, in order to obtain druggable targets to restore Numb levels in these tumors. If successful, our work will elucidate major mechanisms of normal and cancer stem cell regulation, and provide tools for SC-specific therapeutic intervention.
Max ERC Funding
2 274 862 €
Duration
Start date: 2009-03-01, End date: 2014-02-28
Project acronym MOBILE
Project Modelling, Optimization and Control of Biomedical Systems
Researcher (PI) Efstratios Pistikopoulos
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary The main aim of the proposed project is to develop models and model based control and optimization methods and tools for drug delivery systems, which would ensure: (i) Reliable and fast calculation of the optimal drug dosage without the need for an on-line computer while taking into account the specifics and constraints of the patient model (personalised health care) (ii) Flexibility to adapt to changing patient characteristics, (iii) Incorporation of the physician s performance criteria (iv) Safety of the patients (v) Reduced size effects by optimising the drug infusion rates The overall control and optimisation approach will rely on the novel multi-parametric model-based control technology developed by the PI over the past 15 years, which will be further extended and implemented in the context of the following biomedical systems (a) insulin delivery (b) control of anaesthesia and hemodynamic variables, (c) optimal chemotherapy design for anti-cancer (d) optimal control of the chemotherapy for HIV.
Summary
The main aim of the proposed project is to develop models and model based control and optimization methods and tools for drug delivery systems, which would ensure: (i) Reliable and fast calculation of the optimal drug dosage without the need for an on-line computer while taking into account the specifics and constraints of the patient model (personalised health care) (ii) Flexibility to adapt to changing patient characteristics, (iii) Incorporation of the physician s performance criteria (iv) Safety of the patients (v) Reduced size effects by optimising the drug infusion rates The overall control and optimisation approach will rely on the novel multi-parametric model-based control technology developed by the PI over the past 15 years, which will be further extended and implemented in the context of the following biomedical systems (a) insulin delivery (b) control of anaesthesia and hemodynamic variables, (c) optimal chemotherapy design for anti-cancer (d) optimal control of the chemotherapy for HIV.
Max ERC Funding
1 782 925 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym NOTES
Project New Opportunities in Terahertz Engineering and Science
Researcher (PI) Alexander Giles Davies
Host Institution (HI) UNIVERSITY OF LEEDS
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary Over the last 20 years, the study of mesoscopic quantum-confined electronic systems has revealed a wealth of exciting physics. The characteristic energy scale in many important mesoscopic devices such as two-dimensional electron systems, layered semiconductor structures, semiconductor quantum dots, and laterally-confined wires, dots, and other geometries, corresponds to the terahertz (THz) frequency range, which until recently has been difficult to access. Furthermore, invaluable information on the states and dynamics of carriers in condensed matter systems, not obtainable by other techniques, can potentially be accessed though the dynamic (high frequency) electronic response. My vision is to create a step-change in the study of mesoscopic electronic systems by developing and exploiting THz frequency technology to probe the THz frequency/picosecond response of quantum-confined electronic systems. I will develop quasi-optical guided-wave techniques to generate (and detect) single-cycle THz/picosecond electronic pulses adjacent to the mesoscopic system in a cryostat, avoiding the RC bandwidth-limiting problems inherent in previous high frequency (up to the GHz range) electrical measurements. In parallel, I will develop a series of original imaging and spectroscopy technologies based on the THz quantum cascade laser, including continuous wave coherent detection. These will be exploited in a range of proving projects, including phase-stepping interferometry, coherence-gated imaging and, ultimately, depth-resolved THz holography. This programme, comprising the symbiotic development of THz engineering and science, will be unique internationally and will open new opportunities and directions in the study and exploitation of THz frequency electronics and photonics.
Summary
Over the last 20 years, the study of mesoscopic quantum-confined electronic systems has revealed a wealth of exciting physics. The characteristic energy scale in many important mesoscopic devices such as two-dimensional electron systems, layered semiconductor structures, semiconductor quantum dots, and laterally-confined wires, dots, and other geometries, corresponds to the terahertz (THz) frequency range, which until recently has been difficult to access. Furthermore, invaluable information on the states and dynamics of carriers in condensed matter systems, not obtainable by other techniques, can potentially be accessed though the dynamic (high frequency) electronic response. My vision is to create a step-change in the study of mesoscopic electronic systems by developing and exploiting THz frequency technology to probe the THz frequency/picosecond response of quantum-confined electronic systems. I will develop quasi-optical guided-wave techniques to generate (and detect) single-cycle THz/picosecond electronic pulses adjacent to the mesoscopic system in a cryostat, avoiding the RC bandwidth-limiting problems inherent in previous high frequency (up to the GHz range) electrical measurements. In parallel, I will develop a series of original imaging and spectroscopy technologies based on the THz quantum cascade laser, including continuous wave coherent detection. These will be exploited in a range of proving projects, including phase-stepping interferometry, coherence-gated imaging and, ultimately, depth-resolved THz holography. This programme, comprising the symbiotic development of THz engineering and science, will be unique internationally and will open new opportunities and directions in the study and exploitation of THz frequency electronics and photonics.
Max ERC Funding
1 542 600 €
Duration
Start date: 2008-11-01, End date: 2013-10-31
Project acronym NSYS
Project Nonlinear System Identification and Analysis in the Time, Frequency, and Spatio-Temporal Domains
Researcher (PI) Stephen Alec Billings
Host Institution (HI) THE UNIVERSITY OF SHEFFIELD
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary Recent advances in biology, neuro-imaging, the observation of space by satellites, and many other disciplines has lead to an explosion of data and it is now absolutely imperative that a theoretical framework is developed that can be used to analyse this data to identify system dynamic behaviours in a transparent manner to reveal core dynamic behaviours and features. Complex nonlinear behaviours are ubiquitous in the life sciences, neuro-imaging and many other domains but the problems that these challenges raise are also fundamental in many other disciplines and problem domains. The study of complex systems that evolve as a function of time has received enormous attention over the last century and many important results have been established. While there is still much work to do to fully understand this class of systems recent results demonstrate that there is now a unique opportunity to significantly enhance and extend this purely temporal focus both to include nonlinear frequency domain analysis, and to derive results for the important class of spatio-temporal complex systems. The main aim of this proposal is to develop methods for the identification and analysis of the class of severely nonlinear systems, to develop complimentary nonlinear frequency domain identification and analysis methods, and to study the large class of systems that are defined by both spatial and temporal dynamics. In each case the aim is to develop core generic systems approaches that allow the construction of transparent models from recorded data sets that can be related back and analysed in terms of the components of the underlying system. Exemplars will be used throughout as case studies; these will include modelling the magnetosphere, stem cell dynamics, understanding the visual processing in drosophila or fruit fly brain, modelling the link between the recorded fmri signals and neural activity in brain, and the modelling of chemical systems and crystal growth far from equilibrium.
Summary
Recent advances in biology, neuro-imaging, the observation of space by satellites, and many other disciplines has lead to an explosion of data and it is now absolutely imperative that a theoretical framework is developed that can be used to analyse this data to identify system dynamic behaviours in a transparent manner to reveal core dynamic behaviours and features. Complex nonlinear behaviours are ubiquitous in the life sciences, neuro-imaging and many other domains but the problems that these challenges raise are also fundamental in many other disciplines and problem domains. The study of complex systems that evolve as a function of time has received enormous attention over the last century and many important results have been established. While there is still much work to do to fully understand this class of systems recent results demonstrate that there is now a unique opportunity to significantly enhance and extend this purely temporal focus both to include nonlinear frequency domain analysis, and to derive results for the important class of spatio-temporal complex systems. The main aim of this proposal is to develop methods for the identification and analysis of the class of severely nonlinear systems, to develop complimentary nonlinear frequency domain identification and analysis methods, and to study the large class of systems that are defined by both spatial and temporal dynamics. In each case the aim is to develop core generic systems approaches that allow the construction of transparent models from recorded data sets that can be related back and analysed in terms of the components of the underlying system. Exemplars will be used throughout as case studies; these will include modelling the magnetosphere, stem cell dynamics, understanding the visual processing in drosophila or fruit fly brain, modelling the link between the recorded fmri signals and neural activity in brain, and the modelling of chemical systems and crystal growth far from equilibrium.
Max ERC Funding
1 947 104 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym SILAMPS
Project Silicon integrated lasers and optical amplifiers
Researcher (PI) Kevin Peter Homewood
Host Institution (HI) UNIVERSITY OF SURREY
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary "This project is a six year programme of work to develop fully integrated optical emitters, lasers and optical amplifiers in silicon. Recent years have seen tremendous advances in the development of silicon photonic devices. However, the last hurdle to full silicon photonic systems and optical data transfer on and between integrated circuits are electrically pumped optical amplifiers and lasers in silicon using a CMOS compatible technology. Consequently, there have been massive efforts worldwide to search for efficient light emission from silicon. Our team made a major initial breakthrough producing the first LED in bulk silicon - published in NATURE (1997). Although a world first, this device only operated efficiently at low temperatures. This problem was solved using a new nanotechnology - dislocation engineering - reported in NATURE (2001) - and crucially uses only conventional CMOS technology. The development of this into a silicon injection laser and optical amplifiers is the essential next step for high technology high value applications. We have recently made a further breakthrough by obtaining extraordinary optical gain in erbium doped silicon that now offers a realistic route to this goal. Currently the incorporation of lasers and amplifiers on silicon platforms can only be achieved hybridizations of active devices based on III-V materials ""pasted"" on to silicon waveguides and cavities. Gain has been reported using four-wave-mixing and Intel has recently demonstrated a Raman laser in silicon but both rely on purely optical-to-optical transitions and are fundamentally unable to be electrically pumped. We believe we have the only route that has the potential to produce electrically pumped amplifiers and lasers with room and higher temperature operation and that is capable of genuinely being fully integrated into silicon using standard silicon process technology."
Summary
"This project is a six year programme of work to develop fully integrated optical emitters, lasers and optical amplifiers in silicon. Recent years have seen tremendous advances in the development of silicon photonic devices. However, the last hurdle to full silicon photonic systems and optical data transfer on and between integrated circuits are electrically pumped optical amplifiers and lasers in silicon using a CMOS compatible technology. Consequently, there have been massive efforts worldwide to search for efficient light emission from silicon. Our team made a major initial breakthrough producing the first LED in bulk silicon - published in NATURE (1997). Although a world first, this device only operated efficiently at low temperatures. This problem was solved using a new nanotechnology - dislocation engineering - reported in NATURE (2001) - and crucially uses only conventional CMOS technology. The development of this into a silicon injection laser and optical amplifiers is the essential next step for high technology high value applications. We have recently made a further breakthrough by obtaining extraordinary optical gain in erbium doped silicon that now offers a realistic route to this goal. Currently the incorporation of lasers and amplifiers on silicon platforms can only be achieved hybridizations of active devices based on III-V materials ""pasted"" on to silicon waveguides and cavities. Gain has been reported using four-wave-mixing and Intel has recently demonstrated a Raman laser in silicon but both rely on purely optical-to-optical transitions and are fundamentally unable to be electrically pumped. We believe we have the only route that has the potential to produce electrically pumped amplifiers and lasers with room and higher temperature operation and that is capable of genuinely being fully integrated into silicon using standard silicon process technology."
Max ERC Funding
1 928 021 €
Duration
Start date: 2009-01-01, End date: 2014-12-31
