Chemists and physicists at Justus Liebig University Giessen (JLU) have developed a method to assemble organic nanoarchitectures molecule by molecule. To precisely align the molecules in the plane, they use a salt surface on which the molecules can be moved relatively easily. The second tool is the sharp tip of an atomic force microscope, which ends in a single atom or molecule.
This “finger” is used to successively carry out three reaction steps: First, the molecular starting materials are activated to enable a subsequent intermolecular reaction. Then, the previously activated molecular building blocks are pushed together on the surface before the scanning probe tip induces the chemical reaction that leads to the binding of the molecules. These reaction steps are each induced using short voltage pulses applied between the tip and the surface.
The researchers working together in the LOEWE priority PriOSS (principles of surface-supported synthesis strategies) have thus succeeded in answering a question posed by the physicist Richard Feynman as early as 1959 and with which he founded the field of nanotechnology: What would be the impact if we could construct new materials atom by atom? In the early 1990s, engineer K. Eric Drexler formulated the far bolder vision of even having tiny machines perform this task in the future. Such machines would be able to produce almost any nanoarchitecture – assuming chemical stability – and endow them with tailored properties.
Such proposals have been hotly debated for decades. Richard Smalley, winner of the 1996 Nobel Prize in Chemistry, expressed two main counterarguments: First, the individual building blocks (atoms or molecules) could not be aligned precisely enough with the help of the “fingers” (or tools) of such manufacturing machines, since these fingers themselves could not be made infinitely smaller – they would, after all, also consist of atoms. Second, both the molecular building blocks and the products would always stick to the fingers due to adhesion forces. These cogent arguments went down in scientific history as the “fat finger” and the “sticky finger” problems.
The new method circumvents both problems: The inert, i.e., low-reactivity, salt surface takes on the role of a “non-sticky hand,” and the sharp scanning probe tip is the “non-fat finger.” In this way, JLU scientists will be able to produce new organic nanomaterials in the future and systematically investigate how the structure affects their properties. This should make it possible to specifically influence the properties of the nanoarchitectures.
This is particularly interesting for applications in electronic components such as organic field-effect transistors (OFET), light-emitting diodes (OLEDs, e.g. for smartphone displays) or solar cells. In addition, the stepwise induced chemical reactions can provide new insights into the reaction mechanisms of molecules on surfaces.
Structural analysis with machine learning reveals tactics of SARS-CoV-2 virus
In the ability of the virus, the proteins of the SARS Cov-2 virus play a key role in tricking human immune defenses and replicating in patient cells. An international research team with the participation of the Technical University of Munich (TUM) has now compiled the most comprehensive and detailed overview of all 3D structures of the virus proteins available worldwide to date. The evaluation with artificial intelligence methods revealed surprising findings.
How does the SARS-CoV-2 virus manage to evade immune defenses and replicate in the cells of patients? To answer this question, an international research team has assembled the most comprehensive overview of any analysis of the exact three-dimensional shape of SARS-CoV-2 proteins – including the well-known spike protein – available to date.
To compile this overview, the team used high-throughput machine learning. This approach makes it possible to predict structural states of coronavirus proteins based on analyses of related proteins. The database now consists of 2,060 3D models with atomic resolution. All structural models are freely available on the Aquaria-COVID website (https://aquaria.ws/covid).
“This provides an unprecedented level of detail that will help researchers better understand the molecular mechanisms of COVID-19 infection and develop therapies to combat the pandemic, for example by identifying potential new targets for future treatments or vaccines.”
– Burkhard Rost, Chair of Bioinformatics at the TU Munich
The structural map unlocks the compiled knowledge
In a second part of the study, a complementary approach known as human-in-the-loop machine learning was used. Here, a novel visual interface was generated that summarizes everything that is currently known about the three-dimensional shape of SARS-CoV-2 proteins – and what is not.
Researchers can also use the visual interface as a navigation tool to find appropriate structural models for specific research questions. Work with the models has already provided some important clues about how coronaviruses manage to take command in our cells.
How coronaviruses manage to take command in our cells
Using machine learning algorithms, the team identified three coronavirus proteins (NSP3, NSP13, and NSP16) that “mimic” human proteins and successfully fool host cells into thinking they are endogenous proteins working in the best interest of the cell.
Modeling also revealed five coronavirus proteins (NSP1, NSP3, spike glycoprotein, envelope protein, and ORF9b protein) that “misappropriate” or disrupt processes in human cells. In this way, the virus manages to take control, complete its life cycle and spread.
Understanding how the virus works – and how to stop it
“In analyzing these structural models, we also found new clues about how the virus copies its own genome – which is the key process that enables the virus to spread rapidly in infected individuals,” says Burkhard Rost. “The findings from our study bring us closer to understanding how the virus works and what we can do to stop it.”
“The longer the virus circulates, the greater the risk that it will mutate and form new variants like the delta strain,” says Sean O’Donoghue, lead author of the study and a professor at the Garvan Institute in Sydney. “Our resource will help researchers understand how new strains of the virus differ from each other – a piece of the puzzle we hope will help combat emerging variants.”
“Founders’ Prize underscores importance of innovation and science”
Together with their team, Professor Dr. Uğur Şahin, CEO and co-founder of BioNTech, and Dr. Özlem Türeci, Chief Medical Officer and also co-founder, have provided an unspeakably great service to hundreds of millions of people in a vastly changed world. The co-founders of the Mainz-based biopharma company and their team made a significant contribution to the containment of the COVID-19 pandemic by developing the first mRNA-based COVID-19 vaccine. For this achievement, the partners of the German Founders’ Prize – stern, Sparkassen, ZDF and Porsche – awarded the two researchers and co-founders, as well as their entire team, the Special Prize of the German Founders’ Prize on Tuesday [Sept. 14, 2021] in the ZDF capital city studio.
As part of this year’s German Founders Award ceremony, the co-founders conducted a short interview with presenter Barbara Hahlweg via video feed to the ZDF capital studio for the award acceptance.
“We are particularly pleased about the German Founders’ Prize because it underscores how important innovation and science are in achieving noble goals – in this case, in helping to stem the Corona pandemic. In addition, the award emphasizes the importance of spirited and consistent entrepreneurship.”
– Dr. Özlem Türeci
Addressing the vision for starting his own business, Professor Dr. Uğur Şahin said, “While we were working as doctors, we found that we could not help patients with the available resources as well as science could make it possible. We were looking for a way to bring our scientific ideas to patients. It became apparent that this would not be possible in a purely academic setting. We decided to incorporate to be able to realize our vision.”
Before founding the company in 2008, the pair of researchers had founded Ganymed Pharmaceuticals, a biopharmaceutical company, to develop new antibody-based cancer therapies. In 2016, Sahin and Türeci sold their first Unicorn to Japanese pharmaceutical company Astellas. The group also initially focused on cancer research, based on four complementary drug classes. The company’s proprietary mRNA technology is the most advanced of the four classes. The goal was and is to develop innovative individualized therapies for people with cancer. Meanwhile, the company is also researching vaccines and therapies in the field of infectious diseases and autoimmune diseases.
At the first signs of an emerging COVID-19 pandemic, BioNTech decided to do its part by developing a vaccine based on the company’s proprietary mRNA technology, and within a very short period of time, raised resources for this endeavor, which was later named “Project Lightspeed”. In less than a year, the Group worked with U.S. pharmaceutical company Pfizer to develop an effective and well-tolerated COVID-19 vaccine and make it available to people worldwide. The vaccine was the first mRNA-based vaccine ever approved for the market – the birth of a new class of drugs. The world-renowned vaccine has now been administered hundreds of millions of times. A total of 3 billion doses are expected to be produced by the end of the year, and 1.4 billion have already been delivered to more than 100 countries and regions around the world. This will protect more than 15 percent of the world’s population from contracting COVID-19. The success of the vaccine allows BioNTech to accelerate additional programs. In August, the company announced it was developing an mRNA-based vaccine against malaria – a disease that killed nearly 400,000 thousand people in 2019, according to WHO.
Before the COVID-19 pandemic, the company was known only among experts. The company is now highly traded on the stock market – in August, its market value cracked the $100 billion mark. The Mainz-based company now employs more than 2,500 people worldwide, with offices in several German cities, the United States, the United Kingdom and soon Singapore. In addition, BioNTech is investing in the expansion of its own production network. The goal is not only to build regional and global capacities for the growing pipeline of product candidates, but also, in particular, to contribute to the democratization of medicine and healthcare. In addition to an mRNA production facility in Singapore for the Southeast Asia region, the company also plans to build production capacity on the African continent.
The partner representatives of stern, Sparkassen, ZDF and Porsche honored the expertise, commitment, as well as the unbridled research drive with which Dr. Özlem Türeci and Professor Dr. Uğur Şahin and their team have implemented their goal of developing an effective and well-tolerated COVID-19 vaccine as quickly as possible with the special award of the German Founders’ Prize. In addition to the research work, he said, an equally great achievement was to network investors, companies as partners, suppliers and producers in such a way that production and distribution of the vaccine are also possible quickly, effectively and safely. The special prize of the German Founders’ Award is awarded to the two co-founders and their entire team because they show what science and innovation can achieve.
GEA is further expanding its market position in the dynamically growing new food sector with one of the largest orders in the company’s history. Novozymes, the world’s largest supplier of enzyme and microbial technologies based in Denmark, is entrusting GEA with the turnkey equipment of a large-scale plant for the production of plant-based proteins required for the production of plant-based foods. The order is worth well into the upper double-digit million euro range. Construction will begin this year; the new plant in Nebraska, USA, is expected to start production at the end of 2023.
“There is a huge increase in demand for food products that have a demonstrably better environmental performance than conventionally produced products. With our technologies and experience in scaling industrial applications, GEA is ideally positioned to serve the new-food market, contributing to our corporate purpose of ‘engineering for a better world.’ We are pleased to partner Novozymes in this strategic project.”
– Stefan Klebert, CEO
Novozymes has been developing fermented catalytic – i.e. industrially produced – enzymes for decades, which are the basis for applications in numerous industries. Just recently, the company announced plans to invest DKK two billion in the growth market of functional proteins, so-called advanced protein solutions, for the food industry. “The investment in a new state-of-the-art production line in Blair, Nebraska, underscores our commitment to sustainably feeding the world and demonstrating the true power of biotechnology,” said Graziela Chaluppe dos Santos Malucelli, COO and Executive Vice President Novozymes.
The new production facility includes manufacturing steps from harvesting to separation of the protein. According to Heinz-Jürgen Kroner, Senior Vice President Liquid Technologies and responsible for the New Food business in the Group, both partners are united by their ability to build scalable, highly efficient and reliable plants: “The project is exceptional in many respects: the intensive bidding phase led to the planning of the production lines for the ingredients in less than a year. We will go to implementation at the same pace. We are experiencing a very rewarding partnership.”
The company will now build the process equipment – which includes membrane filtration, mixers, homogenizers, heat exchangers, heat treatment equipment, cleaning, filling, and the pump and valve technology – and begin installation in mid-2022. Production is modular, so initial capacity can easily be expanded as demand increases.