ERC FUNDED PROJECTS

Nanostructures drive the world around us. Every modern electronic device contains integrated circuits and nano-electronics to provide its functionality. Advances in nanotechnology directly impact society by enabling smartphones, autonomous devices, the internet of things, data storage, and essentially all forms of advanced technology. Fabricating such nanostructures crucially depends on having the tools to make them visible without destroying them. Modern nanodevices often have complex three-dimensional architectures with small features in all dimensions. While imaging methods that achieve nanometer-scale resolution exist, there are currently no compact tools that can look inside 3D nanostructures made out of metals and semiconductors without damaging their delicate internal structure. I will address this challenge by developing compact tools to image 3D nanostructures in a non-invasive way. Even though most nanostructures are completely opaque to visible light, I will develop light-based methods, combined with computational imaging techniques developed in my previous ERC project, to look inside them with unprecedented resolution and contrast. Light-based imaging is unparalleled in speed and versatility, and allows contact-free detection. My proposal is to: 1) Use compact laser-produced soft-X-ray sources to image nanostructures with high 3D resolution and element-sensitive contrast; 2) Use laser-induced ultrasound pulses to image complex 3D nanostructures, even through strongly absorbing materials; 3) Employ computational imaging methods to reconstruct high-resolution 3D object images from the resulting complex diffraction signals. I will forge a coordinated research program to bring these concepts to reality. This program provides exciting prospects for fundamental science and industrial metrology. I will go beyond the state-of-the-art in nano-imaging, to extend our vision into the complex interior of the smallest structures found in science and technology.

2 000 000 €

Start date: 2020-10-01, End date: 2025-09-30

Due to antibiotic resistance, there is now great interest in the development of antibody-based therapies against bacterial infections, for instance via antibodies that boost the host immune system. In order to kill bacteria, antibodies should trigger activation of the complement cascade, which forms bactericidal Membrane Attack Complex (MAC) pores and strongly enhances phagocytosis. Although the power of complement could be exploited for antibody therapies, such developments are hampered by our limited insights into the mechanisms underlying antibody-dependent complement activation on bacteria. My team has developed unique assays to study complement activation on bacteria. In this proposal, we will combine our function-driven approaches with novel B cell sequencing methods to identify anti-bacterial antibodies with strong complement-activating potential. We will develop novel approaches to identify the variable (VH:VL) sequences of human antibodies that recognize whole bacterial cells. After FACS sorting of memory B cells or yeast Fab display, we will use multi-well functional assays to select monoclonal antibodies driving potent complement activation and subsequent killing of E. coli (via neutrophils or MAC). Thanks to our unique tools and unprecedented insights, we are in an unique position to decipher basic mechanisms by which antibodies induce bacterial killing via neutrophils or MAC. We will combine live-cell imaging and structural approaches to determine how bactericidal antibodies assemble lethal MAC pores in the bacterial cell envelope. Finally, we will explore the design of potent antibody combinations and study the mechanisms by which antibodies steer different effector functions, both in the context of clinical and non-pathogenic E. coli strains. Altogether, this grant will lead to fundamental knowledge about the functioning of the immune system and provide a biological basis for the development of antibody-based therapies against bacteria.

2 000 000 €

Start date: 2021-06-01, End date: 2026-05-31

Replacement of petrochemistry by bio-based processes is key to sustainable development and requires microbes equipped with novel-to-nature capabilities. The efficiency of such engineered microbes strongly depends on their native metabolic networks. However, aeons of evolution have optimized these networks for fitness in nature rather than for industrial performance. As a result, central metabolic networks are complex and encoded by mosaic microbial genomes in which genes, irrespective of their function, are scattered over the genome and chromosomes. This absence of a modular organization tremendously restricts genetic accessibility and presents a major hurdle for fundamental understanding and rational engineering of central metabolism. To conquer this limitation, I introduce the concept of ‘pathway swapping’, which will enable experimenters to remodel the core machinery of microbes at will. Using the yeast Saccharomyces cerevisiae, an industrial biotechnology work horse and model eukaryotic cell, I propose to design and construct a microbial chassis in which all genes encoding enzymes in central carbon metabolism are relocated to a specialized synthetic chromosome, from which they can be easily swapped by any – homologous or heterologous – synthetic pathway. This challenging and innovative project paves the way for a modular approach to engineering of central metabolism. Beyond providing a ground-breaking enabling technology, the ultimate goal of the pathway swapping technology is to address hitherto unanswered fundamental questions. Access to a sheer endless variety of configurations of central metabolism offers unique, new possibilities to study the fundamental design of metabolic pathways, the constraints that have shaped them and unifying principles for their structure and regulation. Moreover, this technology enables fast, combinatorial optimization studies on central metabolism to optimize its performance in biotechnological purposes.

2 149 718 €

Start date: 2015-09-01, End date: 2020-08-31

Two-dimensional transition metal dichalcogenides (2D-TMDs) are an exciting class of new materials. Their ultrathin body, optical band gap and unusual spin and valley polarization physics make them very promising candidates for a vast new range of (opto-)electronic applications. So far, most experimental work on 2D-TMDs has been performed on exfoliated flakes made by the ‘Scotch tape’ technique. The major next challenge is the large-area synthesis of 2D-TMDs by a technique that ultimately can be used for commercial device fabrication. Building upon pure 2D-TMDs, even more functionalities can be gained from 2D-TMD alloys and heterostructures. Theoretical work on these derivates reveals exciting new phenomena, but experimentally this field is largely unexplored due to synthesis technique limitations. The goal of this proposal is to combine atomic layer deposition with plasma chemistry to create a novel surface-controlled, industry-compatible synthesis technique that will make large area 2D-TMDs, 2D-TMD alloys and 2D-TMD heterostructures a reality. This innovative approach will enable systematic layer dependent studies, likely revealing exciting new properties, and provide integration pathways for a multitude of applications. Atomistic simulations will guide the process development and, together with in- and ex-situ analysis, increase the understanding of the surface chemistry involved. State-of-the-art high resolution transmission electron microscopy will be used to study the alloying process and the formation of heterostructures. Luminescence spectroscopy and electrical characterization will reveal the potential of the synthesized materials for (opto)-electronic applications. The synergy between the excellent background of the PI in 2D materials for nanoelectronics and the group’s leading expertise in ALD and plasma science is unique and provides an ideal stepping stone to develop the synthesis of large-area 2D-TMDs and derivatives.

1 968 709 €

Start date: 2015-08-01, End date: 2020-12-31