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A Career Long Effort to Discover a Drug to Treat Neurodegenerative Diseases. My Adventures with γ-Secretase for the Treatment of Alzheimer’s
Full text linkNeurodegenerative diseases encompass a range of chronic diseases marked by the progressive loss of structure or function of the nervous system, particularly within areas of the brain such as the neurons (or nerve cells). This degeneration leads to a decline in cognitive abilities, motor skills, and other neurological functions. The progression can be gradual, occurring over years or even decades, and often leads to significant disability and, ultimately, death. Alzheimer’s disease (AD) is the most prevalent degenerative disease that affects cognition and that rises dramatically with age. It is a progressive, chronic disease that occurs when nerve cells in the brain die. Current treatments largely address symptoms without altering or reversing disease progression. However, recent advancements with amyloid-β (Aβ) antibodies validate Aβ as a therapeutic target for AD. This article details my long-term experience as a medicinal chemist and project leader working on γ-secretase, a key target in AD drug discovery. I will share initial insights from a multi-disciplinary effort to discover a disease modifying treatment for Alzheimer’s disease
Industrializing Biocatalysis
Full text linkBiocatalysis leverages enzymes, nature’s catalysts, to enhance essential steps in chemical synthesis, thereby promoting more sustainable and efficient processes. Enzymes, macromolecular proteins, catalyze reactions with precision and efficiency in all living organisms. These biocatalysts have been honed over millenia for their specific roles within a biological system; however, they can be effectively reengineered to address novel challenges through recent advancements in molecular biology and bioinformatics. In this review, we present selected enzyme sourcing and engineering examples from our laboratory demonstrating the transition of enzymatic processes from academic research to application in Swiss industries
Advancements in Nanoscale Chemical Analysis using Tip-Enhanced Raman Spectroscopy
Full text linkTip-enhanced Raman spectroscopy (TERS) has established itself as a powerful tool in nanoscale chemical analysis, providing unprecedented spatial resolution with high molecular sensitivity and chemical specificity. TERS employs localized surface plasmon resonance at the apex of a sharp scanning probe microscopy tip to overcome the diffraction limit inherent in conventional Raman spectroscopy, achieving spatial resolutions down to the nanometer scale. In this article, we highlight major advancements in TERS over the past five years from our laboratory at ETH Zurich in the following key areas: heterogeneous catalysis, photovoltaic materials, biological membranes, and on-surface molecular assembly. Our recent studies demonstrate the unique capabilities of TERS for in situmonitoring of catalytic reactions, nanoscale mapping of phase behavior in biomembranes, and precise characterization of photovoltaic interfaces. Through these applications, we highlight the potential of TERS for addressing critical challenges across the chemical, biological, and materials sciences. This review serves as a guide for researchers aiming to harness TERS for label-free, non-destructive nanoanalysis to advance understanding of complex molecular materials and processes through ultrahigh sensitivity, specificity, and spatial resolution
Biomanufacturing in Switzerland – Past, Present, and Future
Full text linkChemistry and biotechnology played a central role in transforming a poverty-stricken region in the middle of Europe into a flourishing industrial country. Rural areas remained destitute well into the 18th century. However, during the second half of the 18th century the foundation of the chemical powerhouses was laid. The biotechnological sector was built on these strong fundaments. This paper describes the development of the Swiss biotechnology sector from the early beginnings in the 1930s with a biocatalytic step in Vitamin C production to today’s multifaceted application of biotechnology in Switzerland. As a matter of fact, biotechnology has become a key asset of the contemporary Swiss economy, and this paper outlines what is needed to stay on a successful path
Multiscale Molecular Dynamics Simulations with the MiMiC Framework
Full text linkMultiscale simulations are essential techniques in computational chemistry, providing insights into complex phenomena across extended temporal and spatial scales. With a particular interest in the dynamics of such processes, we developed MiMiC, a framework for efficient multiscale molecular dynamics simulations suited for high-performance computing. One of its key characteristics is a flexible design where external specialized programs handle individual subsystems. This article reviews the core features and some recent advancements in MiMiC, particularly the integration of OpenMM and CP2K
Visions of Dalton: Chemical Education
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Alkene isomerization is key to the functioning of photoreceptors in the retina of mammals; a lack of specific photoreceptors leads to colour blindness, a condition suffered by John Dalton and investigated by him in the late 1700s
Microfluidics for High-Throughput Screening and Directed Evolution in Agrochemical R&D
Full text linkDirected evolution (DE) optimizes biomolecules through natural selection principles, revolutionizing the development of proteins, nucleic acids, and strains for various applications. However, conventional DE methods face limitations in screening throughput, which can prevent the identification of rare but optimal variants within a population. Droplet-based microfluidics enable the transfer of conventional screening methods into nanolitre- scale droplets, enabling high-throughput screening while preserving genotype-phenotype connections. This technology allows rapid screening of millions of variants, opening new possibilities for microbial strain engineering and metabolite production optimization. We discuss the integration of microfluidics into DE workflows and reflect on its potential applications in agrochemical research, including enzyme evolution, crop trait improvement, and natural product biosynthesis