NCCR MSE PI Randall Platt and his colleagues at the D-BSSE in Basel have now developed a molecular recording system that writes transcriptional events into DNA where they can be permanently stored and later accessed to by sequencing.
To create the “recording device” the CRISPR-Cas system was employed, which normally records genetic information about pathogens infecting the cell in a specific stretch of DNA known as a CRISPR array. In their work, the researchers modified the CRISPR-Cas system to be able to translate mRNA molecules arising after exposure to external influences into DNA. In this way they were able to create a biological data logger, a form of synthetic cellular memory, that can be used as a sensor or diagnostic tool in the future. > Read more in English or German
NCCR MSE researchers at the University of Geneva show how electrons can move together on the surface of molecular balls formed of carbon atoms and allow a new type of catalysis.
The Matile group has discovered that C60 fullerene (molecular balls) are excellent catalysts. Their structure is made of 60 carbon atoms arranged in a sphere, thus making them look like a football but 10 million times smaller! They are also called fullerenes, because of their resemblance to the geodesic domes of the American architect Buckminster Fuller. > Read more
Terpenes are the largest class of chemical compounds that are found in nature. They include many essential oils, steroids and clinically relevant substances such as the antimalarial drug artemisinin or the chemotherapy medication paclitaxel.
Despite increasingly refined synthesis methods, chemists have found it very difficult to synthesize these structurally complex compounds in the lab. The process often requires numerous, not always selective synthesis steps, and the yields tend to be low.
Chemists from NCCR MSE working in the Tiefenbacher group have now developed a synthesis method that mimics nature. The decisive step takes place in the cavity of a spherical compound – known as a molecular capsule. > Read more in English or German.
NCCR MSE researchers working in the Mayor and Lörtscher groups have now developed a technique that allows electrical contact to individual molecules to be established. Thousands of stable metal-molecule-metal components can be produced simultaneously by depositing a film of nanoparticles onto the molecules, without compromising the properties of the molecules.
The researchers used a type of sandwich construction in which an interlayer of molecules is brought into contact with metallic electrodes from above and below. The lower electrode consists of a layer of platinum, which is coated with a layer of non-conducting material. Tiny pores are then etched into this layer to produce arbitrary patterns of compartments of different sizes, inside which there is an electrical contact with the platinum electrode. > Read more in English or German.
NCCR MSE researchers working in the Fussenegger group have developed an implant which releases diabetes medication when it senses caffeine in the blood. The future of diabetes treatment might not be a shot in the arm after a meal, but a shot of espresso instead. The scientists hope to transform the lives of diabetics who need regular jabs with an implant that contains hundreds of thousands of designer cells which churn out medicine when they sense caffeine in the bloodstream. > Read more.
Scientists from the NCCR MSE working in the Ward, Matile and Fussenegger groups have designed a mammalian cell with a synthetic gene switch that responds to a cell-penetrating artificial metalloenzyme. The new-to-nature reaction catalyzed by the artificial metalloenzyme promotes a cellular function as the result of turning-on a gene switch. The marriage of synthetic biology and organometallic chemistry opens the door to exploiting new-to-nature chemistry within a living organism. > Read more in English or German.
NCCR MSE researchers working in the Fussenegger group have developed a synthetic gene network that serves as an early warning system for the four most common types of cancer. It recognises those cancers at a very early stage, namely when the level of calcium in the blood is elevated due to the developing tumour. Should a tumour develop, a mole will appear on the skin that is visible to the naked eye. The ability to detect tumours reliably and early would not only save lives, but also reduce the need for expensive, stressful treatment. > Read more in English or German.
Chemists of the NCCR MSE developed a method for reductive amination that relies on the use of visible light and vitamin C. Reductive amination is an important reaction leading to many pharmaceutically relevant products. The new light-driven method developed at University of Basel permits unprecedented spatial and temporal control, as demonstrated by postdoc Xingwei Guo through irradiation of well-defined areas of a solid cellulose support to attach a fluorescent dye. The new method involves the photoinduced formation of highly reactive intermediates, so-called radicals, which are tricky to tame. By exploiting the concept of polarity-matched hydrogen atom transfer and thiol co-catalysts, the controlled interception of these radicals now became possible. The overall reaction involves a two-electron reduction, and light-driven multi-electron transfer is a key research focus in the group of Oliver Wenger.
X. Guo, O. Wenger "Reductive Amination by Photoredox Catalysis via Polarity-Matched Hydrogen Atom Transfer" Angew. Chem. Int. Ed. (2017), DOI: 10.1002/anie.201711467
The Fussenegger group has reprogrammed normal human cells to create designer immune cells capable of detecting and destroying cancer cells. They have built three additional components into human renal cells and (adipose) stem cells, thereby transforming them into synthetic designer cells that mimic T-cells. The artificial T-cell recognises a tumour cell and docks to it. In the process, antenna proteins bend, which triggers a chain reaction. This leads to the killing of the tumor cell. > Read more in English or German.
The Müller group has developed a scale for measuring cells. It allows the weight of individual living cells, and any changes in this weight, to be determined quickly and accurately for the first time. The invention has also aroused significant interest both in and outside the field of biology. > Read more in English or German.
The Vörös group in collaboration with Roche, has developed a completely new method for the analysis of molecules in liquids on a chip. The possible applications of this technology are immense. It has the potential, among other things, to revolutionise medical diagnostics. > Read more in English or German.
The Palivan group has succeeded in developing capsules capable of producing the bio-molecule glucose-6-phosphate that plays an important role in metabolic processes. The researchers were able to produce the metabolite in conditions very similar to the biochemical reaction inside natural cells. The results have been published in the scientific journal Chemical Communications. > Read more in English or German.
Prof. Martin Fussenegger was elected by EMBO as member and by the National Academy of Engineering as foreign member in the class of 2017.
Election to the EMBO Membership is recognition of research excellence. Drawing on the new members’ expertise and insight will be invaluable in helping EMBO to deliver and strengthen its programmes and activities in the years to come. EMBO Members are actively involved in the execution of the organisation’s initiatives by evaluating applications for EMBO funding and by serving on EMBO Council, Committees and Editorial Boards. > Read more
Election to the National Academy of Engineering is among the highest professional distinctions accorded to an engineer. Academy membership honors those who have made outstanding contributions to "engineering research, practice, or education, including significant contributions to the engineering literature" and to "the pioneering of new and developing fields of technology, making major advancements in traditional fields of engineering, or developing/ implementing innovative approaches to engineering education." > Read more
Thomas Ward, Professor of Bioinorganic Chemistry at the University of Basel and Director of the NCCR Molecular Systems Engineering, is the Royal Society of Chemistry Bioinorganic Chemistry Award winner for 2017.
Professor Ward’s group has been combining chemical and biological tools for fifteen years. They create artificial metalloenzymes that can be used for the production of biofuels or as highly specific drugs to target and destroy diseased cells.
The Bioinorganic Chemistry Award is awarded for outstanding research in any aspect of bioinorganic chemistry. Professor Ward said: “I am extremely pleased and honoured to be recognized by the bio-inorganic community. It feels good to be part of this great family of scientists.”
Since 2008 Thomas Ward is Professor for Bioinorganic Chemistry at the University of Basel and 2016 he is the director of the NCCR Molecular Systems Engineering. His research is centered on the exploitation of proteins as host for abiotic cofactors. The resulting artificial metalloenzymes display features reminiscent of both homogeneous catalysts and enzymes. Such systems can be optimized in vivo by Darwinian evolution schemes. > Read more
The Fussenegger group has used the simplest approach yet to produce artificial beta cells from human kidney cells. Like their natural model, the artificial cells act as both sugar sensors and insulin producers, as reported in Science. > Read more in English or German.
Synthetic organic chemistry consists of transforming existing molecules into new molecular structures or assemblies. These new molecular systems are then used in a myriad of ways in everyday life - in a wide range of sectors, such as public health, energy and environment, for use in drugs, solar cells, fragrances, and so on. The active element in the molecule that initiates these transformations, known as the catalyst, is often hydrogen. However, Matile’s group has found that a sulfur atom, if carefully inserted into a molecule, can not only become an extremely effective catalyst but can also operate with greater precision. This discovery, published in Angewandte Chemie, has the potential to revolutionize the world of synthetic organic chemistry. It paves the way for the creation of new molecules that can be used in our daily life. > Read more.
In this NCCR, we employ viruses to restore vision, to program animal cells, or to cure metabolic disorders. With a view to developing new approaches for the directed infection of single animal cells in vitro and in vivo, the Müller and Roska groups quantified the initial binding events of enveloped viruses to animal cells. It was found that within a millisecond, viruses form bonds with positive allosteric modulation to quickly occupy the three binding sites of the viral glycoprotein. This occupation is needed to initiate virus fusion and uptake by the host cell. For more information see Alsteens et al. Nature Nanotechnology (2016).
The Ward and the Panke groups have developed an artificial metalloenzyme that catalyses a reaction inside of cells without equivalent in nature. This could be a prime example for creating new non-natural metabolic pathways inside living cells, as reported in Nature. > Read more. Find the press release in English and German here.
Read the interview in the online-magazine "Compamed" with Cornelia Palivan, project leader of the NCCR Molecular Systems Engineering.
Read Chimia 6/2016 with 12 scientific articles by various research groups from the NCCR Molecular Systems Engineering and an editorial by the directors.
Synthetic biology is an emerging and rapidly evolving engineering discipline. Scientists from the NCCR Molecular Systems Engineering have engineered a chemically switchable version of the light-driven proton pump proteorhodopsin – an essential tool for efficiently powering molecular factories and synthetic cells. > Read more
A negative enzyme yields positive results
Chemistry has provided many key tools and techniques to the biological community in the last twenty years. We can now make proteins that Mother Nature never thought of, image unique parts of live cells and even see cells in live animals. This week in ACS Central Science, two research groups from the NNCR Molecular Systems Engineering show how to design an unnatural protein with new-to-nature capabilities.
Proteins are the workhorses of every cell. They are made up of building blocks called amino acids that are linked up and fold together into functional machines to power every major cellular process. To do these tasks, nature relies on twenty of these blocks together with a few special “co-factors,” often vitamins. However, chemists have discovered clever ways of expanding a protein’s repertoire, engineering in different amino acids or co-factors than you would find in natural biology. Stefan Matile, Thomas Ward and co-workers designed a new co-factor that reverses a classic protein interaction called the cation-π, meaning the stabilization of a positive charge on an electron-rich molecular plane. Nature uses these cation-π interactions to prepare molecules as important as steroids, hormones, vitamins, visual pigments or fragrances, to transduce signals in the brain, to recognize antigens, and so on. Using their new co-factor, and resulting artificial protein, Matile and Ward’s groups collaborated to create the first “anion-π” enzyme, where that electron-rich molecular plane is replaced by an electron-poor plane to stabilize a negative rather than a positive charge during a molecular transformation. In a test tube, proteins with this new-to-nature functionality were able to outperform traditional organic catalysts in an important but unfavourable addition reaction with high specificity and selectivity. They believe their approach can be moved to work in cells and can help make other currently impossible chemical transformations a reality.
The authors acknowledge funding from the National Centres of Competence in Research (NCCR) in Molecular Systems Engineering and in Chemical Biology, the University of Geneva, the University of Basel and the European Research Council.
> Read more here (in German).
For health reasons, Prof. Wolfgang Meier transferred the leadership of the NCCR Molecular Systems Engineering in March 2016 to Prof. Thomas R. Ward of the University of Basel. Wolfgang Meier will pursue his research at the University of Basel and within this NCCR.
Thomas R. Ward now heads the directorate of the NCCR Molecular Systems Engineering, together with co-director Prof. Daniel Müller from ETH Zurich.
More about the NCCR-Directors here.
Prof. Thomas Ward (University of Basel) obtained an ERC advanced grant to realize his DrEAM: the Directed Evolution of Artificial Metalloenzymes in vivo. Read more here (in German).
The Fussenegger-Group makes the headlines with cells that produce insulin on demand: Swiss-TV featured a clip in the news (10 vor 10) and Spiegel Online an article in their science section (both in German). Read their publication here.
Prof. Konrad Tiefenbacher becomes the new assistant professor (tenure track) for the Synthesis of Functional Modules for the NCCR Molecular Systems Engineering.
The call for Konrad Tiefenbacher is the second of three assistant professorships for this NCCR, to be jointly hosted by the University of Basel and ETH Zurich.
Tiefenbacher (36) was born in Vienna (Austria) where he also studied chemistry at the “Technischen Universität Wien”. During his postdoc years, he researched molecular recognition and self-assembly at the Scripps Institute in La Jolla (USA).
Since 2011 he has been a junior professor for organic chemistry at TU Munich where he currently focuses on supramolecular cages as catalytic nanoreactors for chemical transformations. He started his professorship at the Department of Chemistry in the Faculty of Science of the University of Basel on 1 June 2016.
More about Michael Nash: See the Unibasel-website.
Prof. Michael Nash becomes the new assistant professor (tenure track) for the engineering of synthetic systems for the NCCR Molecular Systems Engineering.
The call for Michael Nash is the first of three assistant professorships for this NCCR to be jointly hosted by the University of Basel and ETH Zurich.
Nash (33) was born in Milwaukee (Wisconsin, USA) and started his professorship at the Department of Chemistry in the Faculty of Science at the University of Basel on 1 September 2016. As leader of an interdisciplinary research group at the Ludwig-Maximilians-Universität in Munich he currently focuses on cellulosomal nano-material and the physics of single molecules.
He graduated in 2011 in bioengineering and nanotechnology from the University of Washington, Seattle. His main research interest is developing functional, nanobiological tools for molecular mechanisms in order to build multi-enzyme systems.
More about Michael Nash: See the Unibasel-website.
Dr. Randall J. Platt, formerly postdoctoral fellow at the Massachusetts Institute of Technology (MIT) and at Harvard University, Cambridge (USA), is now Tenure Track Assistant Professor of Biological Engineering at the D-BSSE.
Randall Platt (*1987) works at the intersection of synthetic biology and neurobiology, focusing on developing molecular technologies to understand and treat genetic diseases. Previously he established methods for in vivo genome engineering and has conducted pioneering work on modelling genetic disorders. The technologies he has created have been distributed to hundreds of academic and industry laboratories where it is now being used around the world. Randall Platt is holding joint professorships at ETH Zurich and the University of Basel.
Researchers led by Prof. Yaakov Benenson at D-BSSE of ETH Zurich have developed a biological computer that can speed up the development of therapeutic drugs and reduce cost. Read the publication in Nature Communications and the media release.
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