Project acronym BIOFORCE
Project Simultaneous multi-pathway engineering in crop plants through combinatorial genetic transformation: Creating nutritionally biofortified cereal grains for food security
Researcher (PI) Paul Christou
Host Institution (HI) UNIVERSIDAD DE LLEIDA
Call Details Advanced Grant (AdG), LS9, ERC-2008-AdG
Summary BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways
Summary
BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways
Max ERC Funding
2 290 046 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym CELLDOCTOR
Project Quantitative understanding of a living system and its engineering as a cellular organelle
Researcher (PI) Luis Serrano
Host Institution (HI) FUNDACIO CENTRE DE REGULACIO GENOMICA
Call Details Advanced Grant (AdG), LS2, ERC-2008-AdG
Summary The idea of harnessing living organisms for treating human diseases is not new but, so far, the majority of the living vectors used in human therapy are viruses which have the disadvantage of the limited number of genes and networks that can contain. Bacteria allow the cloning of complex networks and the possibility of making a large plethora of compounds, naturally or through careful redesign. One of the main limitations for the use of bacteria to treat human diseases is their complexity, the existence of a cell wall that difficult the communication with the target cells, the lack of control over its growth and the immune response that will elicit on its target. Ideally one would like to have a very small bacterium (of a mitochondria size), with no cell wall, which could be grown in Vitro, be genetically manipulated, for which we will have enough data to allow a complete understanding of its behaviour and which could live as a human cell parasite. Such a microorganism could in principle be used as a living vector in which genes of interests, or networks producing organic molecules of medical relevance, could be introduced under in Vitro conditions and then inoculated on extracted human cells or in the organism, and then become a new organelle in the host. Then, it could produce and secrete into the host proteins which will be needed to correct a genetic disease, or drugs needed by the patient. To do that, we need to understand in excruciating detail the Biology of the target bacterium and how to interface with the host cell cycle (Systems biology aspect). Then we need to have engineering tools (network design, protein design, simulations) to modify the target bacterium to behave like an organelle once inside the cell (Synthetic biology aspect). M.pneumoniae could be such a bacterium. It is one of the smallest free-living bacterium known (680 genes), has no cell wall, can be cultivated in Vitro, can be genetically manipulated and can enter inside human cells.
Summary
The idea of harnessing living organisms for treating human diseases is not new but, so far, the majority of the living vectors used in human therapy are viruses which have the disadvantage of the limited number of genes and networks that can contain. Bacteria allow the cloning of complex networks and the possibility of making a large plethora of compounds, naturally or through careful redesign. One of the main limitations for the use of bacteria to treat human diseases is their complexity, the existence of a cell wall that difficult the communication with the target cells, the lack of control over its growth and the immune response that will elicit on its target. Ideally one would like to have a very small bacterium (of a mitochondria size), with no cell wall, which could be grown in Vitro, be genetically manipulated, for which we will have enough data to allow a complete understanding of its behaviour and which could live as a human cell parasite. Such a microorganism could in principle be used as a living vector in which genes of interests, or networks producing organic molecules of medical relevance, could be introduced under in Vitro conditions and then inoculated on extracted human cells or in the organism, and then become a new organelle in the host. Then, it could produce and secrete into the host proteins which will be needed to correct a genetic disease, or drugs needed by the patient. To do that, we need to understand in excruciating detail the Biology of the target bacterium and how to interface with the host cell cycle (Systems biology aspect). Then we need to have engineering tools (network design, protein design, simulations) to modify the target bacterium to behave like an organelle once inside the cell (Synthetic biology aspect). M.pneumoniae could be such a bacterium. It is one of the smallest free-living bacterium known (680 genes), has no cell wall, can be cultivated in Vitro, can be genetically manipulated and can enter inside human cells.
Max ERC Funding
2 400 000 €
Duration
Start date: 2009-03-01, End date: 2015-02-28
Project acronym IDRICA
Project Improving Drought Resistance in Crops and Arabidopsis
Researcher (PI) Ana Isabel Caño Delgado
Host Institution (HI) CENTRE DE RECERCA EN AGRIGENOMICA CSIC-IRTA-UAB-UB
Call Details Consolidator Grant (CoG), LS9, ERC-2015-CoG
Summary Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.
Summary
Drought is the first cause of agricultural losses globally, and represents a major threat to food security. Currently, plant biotechnology stands as the most promising strategy to produce crops capable of producing high yields in fed rain conditions. From the study of whole-plants, the main underlying mechanism for responses to drought stress has been uncovered, and multiple drought resistance genes have been engineered into crops. So far, plants with enhanced drought resistance displayed reduced crop yield, which imposes the search of novel approaches to uncouple drought resistance from plant growth. Our laboratory has recently shown, for the first time, that the receptors of Brassinosteroid hormones use cell-specific pathways to allocate different developmental responses during root growth. In particular, we have found that cell-specific components of the stem cell niche have the ability to control cellular responses to stress to promote stem renewal to ensure root growth. Additionally, we have also found that BR mutants are resistant to drought, together opening an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this project, we will use Brassinosteroid signaling in the Arabidopsis root to investigate the mechanism for drought stress resistance in plant and to design novel molecules able to confer resistance to the drought stress. Finally, we will translate our research results and tools into Sorghum bicolor (Sorghum), a crop cereal of paramount importance in fed rain regions of the planet. Our research will impact in science, providing new avenues for the study of hormone signaling in plants, and in society, by providing sustainable solutions for enhance crop production in limiting water environments.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym NONCODRIVERS
Project Finding noncoding cancer drivers
Researcher (PI) Nuria Lopez Bigas
Host Institution (HI) FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Call Details Consolidator Grant (CoG), LS2, ERC-2015-CoG
Summary Finding the mutations, genes and pathways directly involved in cancer is of paramount importance to understand the mechanisms of tumour development and devise therapeutic strategies to overcome the disease. Due to their role in cancer development and maintenance, the proteins encoded by cancer genes are candidate therapeutic targets. Indeed, in recent years we have witnessed the development of successful cancer-targeting therapies to counteract the effect of driver mutations. Although the coding part of the human genome has now largely been explored in the search for cancer driver mutations in most frequent cancer types, the extent of involvement of noncoding mutations in cancer development remains a mystery. The main challenges faced are: 1) the functional role of most noncoding regions is unknown, and 2) tumours often have thousands of somatic mutations, so that distinguishing cancer driver mutations from bystanders is like finding the proverbial needle in a haystack. To overcome these two challenges I propose to analyse the pattern of somatic mutations across thousands of tumours in noncoding regions to identify signals of positive selection. These signals are an indication that mutations in the region have been positively selected during tumour evolution and are thus directly involved in the tumour phenotype. The large scale analysis proposed here will allow us to create a catalogue of noncoding elements involved in different types of cancer upon mutations. We will study in detail a selected set of driver elements to uncover their specific function and role in the tumourigenic process. Furthermore, we will explore possibilities of counteracting their driver effect with targeted drugs. The results of this project may boost our understanding of the biological role of noncoding regions, help to unravel novel molecular causes of cancer and provide novel targeted therapeutic opportunities for cancer patients.
Summary
Finding the mutations, genes and pathways directly involved in cancer is of paramount importance to understand the mechanisms of tumour development and devise therapeutic strategies to overcome the disease. Due to their role in cancer development and maintenance, the proteins encoded by cancer genes are candidate therapeutic targets. Indeed, in recent years we have witnessed the development of successful cancer-targeting therapies to counteract the effect of driver mutations. Although the coding part of the human genome has now largely been explored in the search for cancer driver mutations in most frequent cancer types, the extent of involvement of noncoding mutations in cancer development remains a mystery. The main challenges faced are: 1) the functional role of most noncoding regions is unknown, and 2) tumours often have thousands of somatic mutations, so that distinguishing cancer driver mutations from bystanders is like finding the proverbial needle in a haystack. To overcome these two challenges I propose to analyse the pattern of somatic mutations across thousands of tumours in noncoding regions to identify signals of positive selection. These signals are an indication that mutations in the region have been positively selected during tumour evolution and are thus directly involved in the tumour phenotype. The large scale analysis proposed here will allow us to create a catalogue of noncoding elements involved in different types of cancer upon mutations. We will study in detail a selected set of driver elements to uncover their specific function and role in the tumourigenic process. Furthermore, we will explore possibilities of counteracting their driver effect with targeted drugs. The results of this project may boost our understanding of the biological role of noncoding regions, help to unravel novel molecular causes of cancer and provide novel targeted therapeutic opportunities for cancer patients.
Max ERC Funding
1 995 829 €
Duration
Start date: 2016-12-01, End date: 2021-11-30
