Project acronym COGATIMABIO
Project Combined time domain and spectral domain coherence gating for imaging and biosensing
Researcher (PI) Adrian Podoleanu
Host Institution (HI) UNIVERSITY OF KENT
Call Details Advanced Grant (AdG), LS7, ERC-2009-AdG
Summary Revolutionary combination of principles of spectral domain and time domain coherence gating will be researched. The present proposal puts forward: (i) a novel class of optical interferometers, (ii) a novel class of wavefront sensors and (iii) combinations of imaging channels with the novel wavefront sensors. All these are driven by the needs to address the limitations in terms of speed of the time domain (TD) optical coherence tomography (OCT), in terms of range, resolution and focus of the spectral (SD) OCT methods and in terms of spatial resolution of wavefront sensors. A new class of OCT systems is researched, as a marriage between the TD-OCT and SD-OCT methods. The novel methods present the generality of being compatible with both TD-OCT and SD-OCT. It is envisaged that the research results will revolutionise the field of high resolution imaging and high sensitive sensing and open applications not currently possible with the present OCT, confocal microscopy or multiphoton microscopy technology. The method to be researched will allow versatile functionality in measurements, in 3D imaging of moving tissue and functional/low noise imaging by making use of angular compounding or polarisation. Novel directions are opened in the tracking of the axial position of objects (cornea or retina), automatic dispersion compensation as well as improvement in the synchronism between the coherence gate and the focus in axial scanning. Simultaneous measurements over multiple path lengths becomes feasible, with potential applications in high throughput sensing. The methods proposed open novel avenues in biosensing by amplification of tiny frequency shifts or tiny changes in the optical paths. Possible outcome are high sensitive biosensors, multiple imaging at different depths, fast and long range tracking, long axial scanning, coherence gated wavefront sensors with applications in vision sciences and microscopy, protein identification and contrast agents developments.
Summary
Revolutionary combination of principles of spectral domain and time domain coherence gating will be researched. The present proposal puts forward: (i) a novel class of optical interferometers, (ii) a novel class of wavefront sensors and (iii) combinations of imaging channels with the novel wavefront sensors. All these are driven by the needs to address the limitations in terms of speed of the time domain (TD) optical coherence tomography (OCT), in terms of range, resolution and focus of the spectral (SD) OCT methods and in terms of spatial resolution of wavefront sensors. A new class of OCT systems is researched, as a marriage between the TD-OCT and SD-OCT methods. The novel methods present the generality of being compatible with both TD-OCT and SD-OCT. It is envisaged that the research results will revolutionise the field of high resolution imaging and high sensitive sensing and open applications not currently possible with the present OCT, confocal microscopy or multiphoton microscopy technology. The method to be researched will allow versatile functionality in measurements, in 3D imaging of moving tissue and functional/low noise imaging by making use of angular compounding or polarisation. Novel directions are opened in the tracking of the axial position of objects (cornea or retina), automatic dispersion compensation as well as improvement in the synchronism between the coherence gate and the focus in axial scanning. Simultaneous measurements over multiple path lengths becomes feasible, with potential applications in high throughput sensing. The methods proposed open novel avenues in biosensing by amplification of tiny frequency shifts or tiny changes in the optical paths. Possible outcome are high sensitive biosensors, multiple imaging at different depths, fast and long range tracking, long axial scanning, coherence gated wavefront sensors with applications in vision sciences and microscopy, protein identification and contrast agents developments.
Max ERC Funding
1 999 241 €
Duration
Start date: 2010-05-01, End date: 2015-10-31
Project acronym ONCOGENOMICS
Project Development of high throughput in vivo oncogenomic screening strategies in acute leukaemia
Researcher (PI) Christine Britch
Host Institution (HI) UNIVERSITY OF NEWCASTLE UPON TYNE
Call Details Advanced Grant (AdG), LS7, ERC-2009-AdG
Summary Within a highly successful research environment, we will develop a state-of the-art high throughput functional in vivo oncogenicity assay, using mouse bone marrow transplant models of leukaemia to conclusively identify the important genetic changes involved in the development and progression of cancer. This study will focus on B-lineage acute lymphoblastic leukaemia (ALL), for which there is a wealth of knowledge on the biology of the disease. Our aim will be to differentiate between driver and passenger genes, when other techniques have implicated large numbers of candidates. Initial areas of focus will be 1) to determine the gene(s) involved in patients with the poor risk subtype of ALL, iAMP21, so that these may be specifically targeted by molecular therapy. This is important to reduce the high level of toxic treatment required to prevent relapse in these patients; 2) to definitively identify tumour suppressor genes within the deleted region of chromosome 6. Patients with this abnormality comprise a high proportion of ALL and non Hodgkin s lymphoma (NHL), particularly childhood T-lineage NHL, where it is linked to a poor prognosis; 3) to identify and characterise those genes involved in drug resistance leading to relapse. Candidate tumour suppressor genes associated with relapse have already been implicated. Comprehensive sequencing of further samples will identify additional mutated genes. The ultimate aim is to determine the clinical relevance of these abnormalities and develop molecular genetic assays suitable for routine clinical detection, with a view to validating their role as molecular targets for therapy; a particular strength of my group. In the future this methodology will be extended to the detection of genes in other haematological malignancies.
Summary
Within a highly successful research environment, we will develop a state-of the-art high throughput functional in vivo oncogenicity assay, using mouse bone marrow transplant models of leukaemia to conclusively identify the important genetic changes involved in the development and progression of cancer. This study will focus on B-lineage acute lymphoblastic leukaemia (ALL), for which there is a wealth of knowledge on the biology of the disease. Our aim will be to differentiate between driver and passenger genes, when other techniques have implicated large numbers of candidates. Initial areas of focus will be 1) to determine the gene(s) involved in patients with the poor risk subtype of ALL, iAMP21, so that these may be specifically targeted by molecular therapy. This is important to reduce the high level of toxic treatment required to prevent relapse in these patients; 2) to definitively identify tumour suppressor genes within the deleted region of chromosome 6. Patients with this abnormality comprise a high proportion of ALL and non Hodgkin s lymphoma (NHL), particularly childhood T-lineage NHL, where it is linked to a poor prognosis; 3) to identify and characterise those genes involved in drug resistance leading to relapse. Candidate tumour suppressor genes associated with relapse have already been implicated. Comprehensive sequencing of further samples will identify additional mutated genes. The ultimate aim is to determine the clinical relevance of these abnormalities and develop molecular genetic assays suitable for routine clinical detection, with a view to validating their role as molecular targets for therapy; a particular strength of my group. In the future this methodology will be extended to the detection of genes in other haematological malignancies.
Max ERC Funding
2 249 440 €
Duration
Start date: 2010-05-01, End date: 2016-04-30
Project acronym OPTIMISE
Project Optical Platform for Therapy and diagnostic Imaging in Minimally Invasive Surgical Endoscopy
Researcher (PI) Daniel Stuart Elson
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), LS7, ERC-2009-StG
Summary With the clinical drive for earlier detection of disease and minimally invasive treatment, there is a paradigm shift of imaging and therapy towards in vivo, in situ surgery. One major effort towards this goal is the translation of emerging optical diagnostic imaging and therapy techniques into minimally invasive surgery (MIS) and cancer screening. This proposal will develop a novel multimodal platform that can be deployed in flexible endoscopy and robotic assisted MIS devices. This is timely in that recently there have been advances in the optical detection of diseased tissue states and also in nanotechnology that allows photothermal therapies based on focused optical energy delivery to gold nanoparticles. The clinical integration of these two strands of research offers significant promise for optical adjuvant cancer therapies and for image-guided tissue fusion, but the study of the therapeutic effect of these techniques has been limited due to the lack of a common platform for image-guided optical follow-up of the therapy. The purpose of this proposal is to develop a programmable light source for simultaneous multimodal screening and image-guided nanoparticle-mediated thermal therapy. The platform will be validated by studying of diseases of the colon to enable detection and treatment of flat polyps that may develop into invasive cancers. As a young lecturer, Dr Elson has extensive multidisciplinary experience in laser technology, biophotonics, optical imaging, microscope technique development, minimally invasive surgery and robotic-assisted surgery. He will bring together new technology with a mix of engineering, biochemistry and biophotonics skills. The proposed work will be carried out in state-of-the-art facilities with access to the clinic for translation.
Summary
With the clinical drive for earlier detection of disease and minimally invasive treatment, there is a paradigm shift of imaging and therapy towards in vivo, in situ surgery. One major effort towards this goal is the translation of emerging optical diagnostic imaging and therapy techniques into minimally invasive surgery (MIS) and cancer screening. This proposal will develop a novel multimodal platform that can be deployed in flexible endoscopy and robotic assisted MIS devices. This is timely in that recently there have been advances in the optical detection of diseased tissue states and also in nanotechnology that allows photothermal therapies based on focused optical energy delivery to gold nanoparticles. The clinical integration of these two strands of research offers significant promise for optical adjuvant cancer therapies and for image-guided tissue fusion, but the study of the therapeutic effect of these techniques has been limited due to the lack of a common platform for image-guided optical follow-up of the therapy. The purpose of this proposal is to develop a programmable light source for simultaneous multimodal screening and image-guided nanoparticle-mediated thermal therapy. The platform will be validated by studying of diseases of the colon to enable detection and treatment of flat polyps that may develop into invasive cancers. As a young lecturer, Dr Elson has extensive multidisciplinary experience in laser technology, biophotonics, optical imaging, microscope technique development, minimally invasive surgery and robotic-assisted surgery. He will bring together new technology with a mix of engineering, biochemistry and biophotonics skills. The proposed work will be carried out in state-of-the-art facilities with access to the clinic for translation.
Max ERC Funding
1 616 146 €
Duration
Start date: 2009-12-01, End date: 2015-09-30
Project acronym SCINSCEF
Project Repair Spinal Cord Injury by Controlling Migration of Neural Stem Cells - multidiciplinary approaches of electric stimulation and nanotechnology
Researcher (PI) Bing Song
Host Institution (HI) CARDIFF UNIVERSITY
Call Details Starting Grant (StG), LS7, ERC-2009-StG
Summary Millions of people worldwide suffer from spinal cord injury (SCI), with devastating consequences and costs. Various clinical approaches have been attempted to treat SCI with little satisfaction due to the limitation of self-regeneration of axons. Neural stem cell transplantation is an alternative approach with great potential to treat SCI, but the mechanisms controlling migration of implanted stem cells are unclear. A recent SCI clinical trial using implanted electric stimulators to promote axon regeneration showed promising results. However, the mechanism underpinning this technique also remains elusive. We shall investigate genes and molecules regulating the electric fields controlled neural stem cells migration. We have shown before that electric signals play essential roles in directing cell migration during wound healing, and that PI3K and PTEN are critical in the regulation of this event (Zhao, Song et al. Nature 2006). Pax6 and ephrin are also proved to be important in guiding cell migration, however the interactions between PI3K, PTEN and Pax6, Eph-ephrin pathways are unknown. We shall further investigate their potential interactions in this project.. Apart from electric signals, neural stem cell migration can be also regulated by chemical, physical, and haptotactic guidance cues. This project shall use multidisciplinary approaches to combine neural stem cells transplantation with electric stimulation and nanotechnology, to optimize a novel stem cell replacement therapy. We shall use multiple peptide structures to engineer diverse adhesion peptide motifs on the nanofibers, and embed EGF/bFGF into 3D nanofibers scaffold to encapsulate neural stem cells for the transplantation study. These shall be tested in both 2D / 3D in vitro and in SCI animal models in vivo.
Summary
Millions of people worldwide suffer from spinal cord injury (SCI), with devastating consequences and costs. Various clinical approaches have been attempted to treat SCI with little satisfaction due to the limitation of self-regeneration of axons. Neural stem cell transplantation is an alternative approach with great potential to treat SCI, but the mechanisms controlling migration of implanted stem cells are unclear. A recent SCI clinical trial using implanted electric stimulators to promote axon regeneration showed promising results. However, the mechanism underpinning this technique also remains elusive. We shall investigate genes and molecules regulating the electric fields controlled neural stem cells migration. We have shown before that electric signals play essential roles in directing cell migration during wound healing, and that PI3K and PTEN are critical in the regulation of this event (Zhao, Song et al. Nature 2006). Pax6 and ephrin are also proved to be important in guiding cell migration, however the interactions between PI3K, PTEN and Pax6, Eph-ephrin pathways are unknown. We shall further investigate their potential interactions in this project.. Apart from electric signals, neural stem cell migration can be also regulated by chemical, physical, and haptotactic guidance cues. This project shall use multidisciplinary approaches to combine neural stem cells transplantation with electric stimulation and nanotechnology, to optimize a novel stem cell replacement therapy. We shall use multiple peptide structures to engineer diverse adhesion peptide motifs on the nanofibers, and embed EGF/bFGF into 3D nanofibers scaffold to encapsulate neural stem cells for the transplantation study. These shall be tested in both 2D / 3D in vitro and in SCI animal models in vivo.
Max ERC Funding
1 759 613 €
Duration
Start date: 2010-01-01, End date: 2015-12-31
Project acronym TREATSKIN
Project Tissue engineering to evaluate novel treatments for skin cancer and genetic disease
Researcher (PI) Irene May Leigh
Host Institution (HI) UNIVERSITY OF DUNDEE
Call Details Advanced Grant (AdG), LS7, ERC-2009-AdG
Summary As our understanding of disease translates from basic science to clinical application there is a need for robust preclinical models to test interventions and therapies, which mirror the clinical situation and likely outcomes. This will assist key stage decision making before costly clinical trials are commenced. Skin diseases represent a significant health burden. Non-melanoma skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common human malignancies. Genetic skin diseases, or genodermatoses, are heritable conditions comprising nearly 300 distinct often rare clinical entities, which affect ~30M people in Europe i.e. ~7% of the entire population (http://geneskin.idi.it/homepgs/rareg.php). Thus, genodermatoses have important medical and social implications and have very limited therapeutic possibilities. This proposal will develop preclinical models which can be used to identify therapeutic targets for the treatment of skin cancer and to explore novel approaches to gene and cell therapy. Organotypical tissue engineered skin constructs combining normal, malignant and diseased epithelial, mesenchymal and connective tissue elements will first be used to examine the effect of tumour microenvironment on cancer cell invasion. Then constructs mimicking 1. intraepithelial, 2. well and 3. poorly differentiated SCCs will be used as surface xenotransplants. Optimisation will examine the contribution of adipocyte and mesenchymal stem cells. A set of genes identified as a characteristic SCC signature by extensive previous studies will then be genetically manipulated to examine the effects of up and down regulation of these genes in tumour progression and invasion. The effects of novel small molecules will also be tested. Surface xenotransplants of organotypical cultures of genetically diseased keratinocytes will be established to assess the long term outcomes of comparing ex vivo gene therapy with protein and cell therapy.
Summary
As our understanding of disease translates from basic science to clinical application there is a need for robust preclinical models to test interventions and therapies, which mirror the clinical situation and likely outcomes. This will assist key stage decision making before costly clinical trials are commenced. Skin diseases represent a significant health burden. Non-melanoma skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common human malignancies. Genetic skin diseases, or genodermatoses, are heritable conditions comprising nearly 300 distinct often rare clinical entities, which affect ~30M people in Europe i.e. ~7% of the entire population (http://geneskin.idi.it/homepgs/rareg.php). Thus, genodermatoses have important medical and social implications and have very limited therapeutic possibilities. This proposal will develop preclinical models which can be used to identify therapeutic targets for the treatment of skin cancer and to explore novel approaches to gene and cell therapy. Organotypical tissue engineered skin constructs combining normal, malignant and diseased epithelial, mesenchymal and connective tissue elements will first be used to examine the effect of tumour microenvironment on cancer cell invasion. Then constructs mimicking 1. intraepithelial, 2. well and 3. poorly differentiated SCCs will be used as surface xenotransplants. Optimisation will examine the contribution of adipocyte and mesenchymal stem cells. A set of genes identified as a characteristic SCC signature by extensive previous studies will then be genetically manipulated to examine the effects of up and down regulation of these genes in tumour progression and invasion. The effects of novel small molecules will also be tested. Surface xenotransplants of organotypical cultures of genetically diseased keratinocytes will be established to assess the long term outcomes of comparing ex vivo gene therapy with protein and cell therapy.
Max ERC Funding
1 999 999 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
