ERC FUNDED PROJECTS

During the 20th century computer technology evolved from bulky, slow, special purpose mechanical engines to the now ubiquitous silicon chips and software that are one of the pinnacles of human ingenuity. The goal of the field of molecular programming is to take the next leap and build a new generation of matter-based computers using DNA, RNA and proteins. This will be accomplished by computer scientists, physicists and chemists designing molecules to execute ``wet'' nanoscale programs in test tubes. The workflow includes proposing theoretical models, mathematically proving their computational properties, physical modelling and implementation in the wet-lab. The past decade has seen remarkable progress at building static 2D and 3D DNA nanostructures. However, unlike biological macromolecules and complexes that are built via specified self-assembly pathways, that execute robotic-like movements, and that undergo evolution, the activity of human-engineered nanostructures is severely limited. We will need sophisticated algorithmic ideas to build structures that rival active living systems. Active-DNA, aims to address this challenge by achieving a number of objectives on computation, DNA-based self-assembly and molecular robotics. Active-DNA research work will range from defining models and proving theorems that characterise the computational and expressive capabilities of such active programmable materials to experimental work implementing active DNA nanostructures in the wet-lab.

2 349 603 €

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

Dysregulation of capillary permeability is a severe problem in critically ill patients, but the mechanisms involved are poorly understood. Further, there are no targeted therapies to stabilize leaky vessels in various common, potentially fatal diseases, such as systemic inflammation and sepsis, which affect millions of people annually. Although a multitude of signals that stimulate opening of endothelial cell-cell junctions leading to permeability have been characterized using cellular and in vivo models, approaches to reverse the harmful process of capillary leakage in disease conditions are yet to be identified. I propose to explore a novel autocrine endothelial permeability regulatory system as a potentially universal mechanism that antagonizes vascular stabilizing ques and sustains vascular leakage in inflammation. My group has identified inflammation-induced mechanisms that switch vascular stabilizing factors into molecules that destabilize vascular barriers, and identified tools to prevent the barrier disruption. Building on these discoveries, my group will use mouse genetics, structural biology and innovative, systematic antibody development coupled with gene editing and gene silencing technology, in order to elucidate mechanisms of vascular barrier breakdown and repair in systemic inflammation. The expected outcomes include insights into endothelial cell signaling and permeability regulation, and preclinical proof-of-concept antibodies to control endothelial activation and vascular leakage in systemic inflammation and sepsis models. Ultimately, the new knowledge and preclinical tools developed in this project may facilitate future development of targeted approaches against vascular leakage.

1 999 770 €

Start date: 2018-05-01, End date: 2023-04-30

Recent advances in systems-level study of cells and organisms have revealed the enormous potential to live more sustainably through better use of biological processes. Plants sustainably synthesize the most abundant and diverse materials on Earth. By applying recent advances in life science technology, we can better harness renewable plant resources and bioconversion processes, to develop environmentally and politically sustainable human enterprise and lifestyles. At the same time, the global market for high-value biochemicals and bioplastics from forest and agricultural sources is rapidly increasing, which presents new opportunities for forest and agricultural sectors. The overall aim of BHIVE is to illuminate uncharted regions of genome and metagenome sequences to discover entirely new protein families that can be used to sustainably synthesize novel, high-value biomaterials from renewable plant resources. The approach will include three parallel research thrusts: 1) strategic analysis of transcriptome and metagenome sequences to identify proteins with entirely unknown function relevant to biomass (lignocellulose) transformation, 2) mapping of uncharted regions within phylogenetic trees of poorly characterized enzyme families with recognized potential to modify the chemistry and biophysical properties of plant polysaccharides, and 3) the design and development of novel enzyme screens to directly address the increasing limitations of existing assays to uncover entirely new protein functions. BHIVE will be unique in its undivided focus on characterizing lignocellulose-active proteins encoded by the 30-40% of un-annotated sequence, or genomic “dark matter”, typical of nearly all genome sequences. In this way, BHIVE tackles a key constraint to fully realizing the societal and environmental benefits of the genomics era.

1 977 781 €

Start date: 2015-09-01, End date: 2020-12-31

"Large bodies usually follow the classical equations of motion. Deviations from this can be called macroscopic quantum behavior. These phenomena have been experimentally verified with cavity Quantum Electro Dynamics (QED), trapped ions, and superconducting Josephson junction systems. Recently, evidence was obtained that also moving objects can display such behavior. These objects are micromechanical resonators (MR), which can measure tens of microns in size and are hence quite macroscopic. The degree of freedom is their vibrations: phonons. I propose experimental research in order to push quantum mechanics closer to the classical world than ever before. I will try find quantum behavior in the most classical objects, that is, slowly moving bodies. I will use MR's, accessed via electrical resonators. Part of it will be in analogy to the previously studied macroscopic systems, but with photons replaced by phonons. The experiments are done in a cryogenic temperature mostly in dilution refrigerator. The work will open up new perspectives on how nature works, and can have technological implications. The first basic setup is the coupling of MR to microwave cavity resonators. This is a direct analogy to optomechanics, and can be called circuit optomechanics. The goals will be phonon state transfer via a cavity bus, construction of squeezed states and of phonon-cavity entanglement. The second setup is to boost the optomechanical coupling with a Josephson junction system, and reach the single-phonon strong-coupling for the first time. The third setup is the coupling of MR to a Josephson junction artificial atom. Here we will access the MR same way as the motion of a trapped ions is coupled to their internal transitions. In this setup, I am proposing to construct exotic quantum states of motion, and finally entangle and transfer phonons over mm-distance via cavity-coupled qubits. I believe within the project it is possible to perform rudimentary Bell measurement with phonons."

2 004 283 €

Start date: 2015-01-01, End date: 2019-12-31