ERC FUNDED PROJECTS

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

2 290 046 €

Start date: 2009-04-01, End date: 2014-03-31

Man and man-made electronic systems share the same ecosystem, and yet work radically differently. Human metabolism uses ion gradients across insulated membranes to simultaneously process slow analog chemical reactions and communicate information in multicellular systems via soluble/volatile molecular signals. By contrast, electronic systems use multicore central processing units to control the flow of electrons through insulated metal wires with gigahertz frequency and communicate information across networks via wired/wireless connections. With the advent of the internet of things, networks of interconnected electronic devices will reach the processing complexity of living systems, yet they remain largely incompatible with biological systems. Wearable electronics can profile physical parameters such as steps and heartbeat, and Google’s proposal to develop glucose-monitoring contact lenses has triggered a wave of interest in harnessing the full potential of bioelectronics for medical applications. Yet this vision remains limited to diagnostics. Capitalizing on our mind-controlled and smartphone-adjustable optogenetic drug-dosing devices, ElectroGene will establish the foundations of electrogenetics, the science of creating electro-genetic interfaces that enable direct two-way communication between electronic devices and living cells. ElectroGene consists of three pillars, (i) voltage-triggered gene expression, (ii) genetically programmed electronics and (iii) wireless-powered implants providing closed-loop bioelectronic control, which allow real-time monitoring of metabolic conditions (diagnosis), enable remote-controlled production and dosing of protein therapeutics by implanted designer cells (treatment), and manage closed-loop control between cells and electronics, thus linking diagnosis and therapy to block disease onset (prevention). ElectroGene design principles and devices will be validated in proof-of-concept preclinical studies for the treatment of diabetes.

2 500 000 €

Start date: 2018-11-01, End date: 2023-10-31

Engineering bacteria to deliver therapeutic agents or to present antigens for vaccination is an emerging area of research with great clinical potential. The most challenging issue in this field is the selection of the right bacteria to engineer, commonly known as “chassis”. The best chassis depends on the application but there is a common drawback in bacteria used nowadays: their complexity and the lack of quantitative information for many reactions which limits genome engineering to classical trial and error approaches. In this project, we want to engineer the genome-reduced bacterium M. pneumoniae using a whole-cell model that will drive the rational to create a chassis for human and animal therapy. Its small size (816 Kbases), the lack of cell wall, and the vast amount of comprehensive quantitative –omics datasets makes this bacterium one of the best candidates for chassis design. By combining bioinformatics, -omics, and biochemistry approaches with genome engineering tools, systems biology analyses, and computational whole-cell models, MYCOCHASSIS aims to: i) develop a whole cell-model based on organism-specific experimental data that will be validated experimentally and that can predict the impact of genome modifications; ii) implement genome engineering tools to delete non-essential pathogenic and virulent elements predicted by the whole-cell model to engineer a therapeutical chassis; iii) using the whole-cell model design and engineer genes and circuits to improve growth rate in a defined medium. iv) as a proof of concept introduce orthogonal gene circuits to secrete peptides and enzymes capable of dissolving in vitro biofilms made by the lung pathogens Pseudomonas aeruginosa and Staphylococus aureus. This project will validate the usefulness of whole-cell models for synthetic biology by modelling multiple genomic modifications orientated to facilitate engineering of biological systems.

2 454 522 €

Start date: 2015-11-01, End date: 2020-10-31

Since living memory, the basic treatment strategies for the therapy of human diseases has not much changed conceptually. Although the molecular understanding of metabolic disorders continues to progress significantly the therapeutic strategy is still based on specific, often heterologous compounds which interfere with critical disease targets, trigger a metabolic bypass reaction or complement a molecular deficiency. As systems biology is revealing gene-function correlations and metabolic network dynamics at great pace and synthetic biology enables bottom-up de-novo design of genetic devices with predictable behaviour, time has now come to develop novel treatment strategies. Prosthetic genetic networks are expected to play a central part of such future treatment strategies. Prosthetic networks are synthetic sensor/effector devices or molecular prostheses which, upon integration into cells and functional connection to their metabolism, monitor disease-relevant metabolites, process off-level concentrations and coordinate adjusted diagnostic, preventive or therapeutic responses in a seamless, automatic and self-sufficient manner. Using a synthetic biology approach and capitalizing on our pioneering prosthetic network designed to control urate homeostasis and treat the tumour lysis syndrome as well as gouty arthritis, ProNet is a highly integrated, multiparallel and interdisciplinary effort to provide a series of prosthetic sensor/effector circuits for precise trigger-control of therapeutic transgenes. ProNet will focus on providing novel treatment opportunities for diabetes and obesity, two core pathologies of the metabolic syndrome, which is on its way to become the top epidemic of the 21st century. ProNet may provide new opportunities for the treatment strategies of the future thereby making the classic therapy of taking pills and getting injections in specified amounts and at particular times likely to become a thing of the past.

2 498 800 €

Start date: 2013-05-01, End date: 2018-04-30