• The Protein Engineers

    Interdisciplinary Bayer Teams Accelerating Life Science Research

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    High-throughput high-tech: Dr. Wayne Coco uses fully automated robot systems as a tool in the development of therapeutic antibodies. In this photo, autonomous robots operate incubators, pipetters and detection systems.

Bayer scientists are working in interdisciplinary teams to search for new targets for active substances or diagnostic options. Synergies in medical and crop protection research result in completely new approaches, from the design of therapeutic antibodies to improved production of new crop protection products. One key to success is highly effective protein molecules, ­constructed in Bayer’s laboratories by protein engineers.

Story check

  • Challenge:
    Highly effective protein molecules play an important role in both medical and crop protection research. They are not just suitable as active ingredients, but also serve as reaction helpers in large-scale chemical production. 
  • Solution:
    The Nimbus Initiative was launched to more efficiently exploit the talents of protein experts throughout the Bayer world. Interdisciplinary teams from the subgroups are work together in a cross-company approach.
  • Benefits:
    It is not just the transfer of knowledge that is growing throughout the Group, but also the rapid generation of improved product development candidates that are resulting from joint projects.  This shortens development cycles to deliver better products – and ultimately, it is doctors, patients, farmers and consumers who benefit.

The biological tools are small but indispensable: enzymes are protein building blocks that keep the respiratory, metabolic and immune systems functioning, and people, animals and plants alive. These biocatalysts are like molecular workhorses and they play a central role in every single cell. They are the reason why special chemical reaction paths are taken: enzymes are particularly effective at opening and relinking only selected molecular bonds. The number of naturally existing enzymes is estimated at more than 10,000.

A Visit to the Protein Engineers

Improving the Quality of ­Biotechnology Research

“Out of this treasure trove of enzymes, biotechnologists have long been discovering numerous ‘chemistry talents’ that they are now utilizing and optimizing as miniature tools for specific purposes,” says Dr. Wayne Coco, Head of Protein Engineering at Bayer HealthCare in Cologne, Germany. The range of applications of these versatile molecules is enormous: the protein building blocks are not only valuable helpers in the body but can also be used as catalysts in large-scale chemical production.

Dr. Mark James Ford

We can now use the talents of enzymes throughout the Bayer Group.

Bayer intends to expand its know-how and technologies relating to these miniature biological tools and increase its efficiency in this area. With this aim specifically in sight, Bayer has initiated two projects, “Biotransformations” and “Protein Engineering,” as part of the Nimbus initiative, which aims to foster closer networking in life sciences among the departments of the Bayer subgroups, and promote the exchange of information with the objective of leveraging synergies to find approaches for new active ingredients and their production.

Strategy against Tumors

Antibodies are an integral part of the natural immune response. The ability of these proteins to recognize certain cell characteristics is a property that Bayer researchers are using to target and destroy cancer cells. For example, antibodies are used to specifically block important metabolic signals that are crucial for the growth or survival of cancer cells.

The intensive dialog across geographic sites and specialist disciplines has not just improved the quality of biotechnology research. “The Nimbus initiative brings together specialists from different disciplines to enable cross-subgroup research projects,” reports Coco. As a molecular biologist and head of the Protein Engineering Nimbus project, he and his team are focused above all on the design of therapeutic antibodies – in other words, special protein molecules that are used in areas such as cancer therapy. “We engineer these proteins to ensure their safety and efficacy,” explains Coco. To do this, ­Bayer’s researchers intervene specifically in the blueprint of a protein that is found in a specific gene sequence. They produce thousands of variations of this candidate and then test them in the laboratory in a fully automated, robot-based high-throughput screening procedure “until we find a suitable protein among the wide range of candidates,” the protein engineer says.

The number of naturally occurring enzymes is estimated at more than

10,000 

The Cologne-based team’s know-how with regard to how to design enhanced antibodies can also be applied to a wide variety of protein optimization goals within the scope of Nimbus projects. For Bayer CropScience, such technologies are extremely interesting because they accelerate the search for new protein-based plant traits and broaden the foundation of this process. “Cooperation with ­Bayer HealthCare’s researchers within the ­Nimbus project gives us access to a highly innovative technology platform, including robot facilities for high-throughput tests,” explains Dr. Marc Linka, who is working on the development of novel traits together with his colleagues at Bayer CropScience.

Research Breakthroughs Are a Matter of Teamwork

Science thrives on the exchange of experiences – and there are plenty of opportunities for this when it comes to the health of people, animals and plants. The Bayer Group is now focusing more closely on these interfaces, and initiated the Nimbus Initiative to this end back in 2012 (see also research 26, Special Feature). The company has provided EUR 30 million for new research projects aimed at more closely interlinking the life sciences. The researchers are working on issues such as epigenetics, high-throughput screening for drug discovery and biotransformations. Their objective: to more intensively exchange acquired knowledge and further improve the quality of research.

Protein Engineering Enhances Crop Traits

This teamwork has already borne fruit: within the scope of the collaboration, the Bayer researchers have constructed several new proteins that are now being integrated into crops and then studied in greenhouses and field tests. “The entire Nimbus team is of course looking forward with great anticipation to see whether the promising results from the laboratory are confirmed in practice,” says Linka.

Dr. Michael Strerath and Konrad Odendahl (left to right) check the pipetting quality of a screening system.
While their colleagues Petra Helfrich and Fabian Scholz (left to right) use the new proteins for initial biotransformations in the Berlin fermentation laboratory.

The protein engineering expertise of Coco’s Cologne-based Bayer team is ­also in demand in other areas – such as designing proteins that can be used as biocatalysts to create production routes for new active substance candidates. They are frequently also suited for establishing more cost-effective production processes.

Interdisciplinary Scientists Work to Improve Production Processes

“The Nimbus project makes it possible for us to systematically exchange biocatalysts between crop protection and pharmaceuticals research for the first time,” explains Dr. Ingo Hartung, Head of BHC’s Biocatalysis group in Berlin. “And with the team of colleagues headed by Wayne ­Coco, we also have the specialists we need to optimize them perfectly and give them the requisite finishing touches.”

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Library of biocatalysts in service: first hits are identified from the collection of microorganisms in Berlin

Yet how can enzymes worth optimizing be identified? The Biotransformation Nimbus project was initiated to answer this question and leverage the potential of the biocatalysts in all areas of the Bayer Group – from their discovery to their production. An interdisciplinary team headed up by Dr. Mark James Ford from Process Research at Bayer CropScience has been working for nearly two years to establish a Group-wide enzyme collection. The team has undertaken to realize technical biotransformations for improved production processes, as well as to explore the spectrum of further application opportunities in research and development. “The knowledge required to systematically exploit biocatalysts already existed to some extent prior to the launch of the Nimbus project,” explains Ford. Yet the transfer of knowledge and direct cooperation between the individual experts have improved substantially as a result of the Group-wide initiative – and ultimately enabled the realization of customized enzymes. “We had no idea just how much we could achieve together: this is synergy in the most positive sense of the word,” says Ford.

The Nimbus project makes it possible for us to systematically exchange biocatalysts between crop protection and pharmaceuticals research for the first time.

Protein-Ingenieure

Together with colleagues, Dr. André Pütz from Bayer Technology Services is constantly working on finding, ­isolating and characterizing new biocatalysts.

Within the Nimbus team, specialists from Bayer Technology Services are working on establishing an extensive enzyme collection. “Through academic interactions as well as extensive literature and database searches, we acquire enzymes of interest which are subsequently prepared in the lab ready for the problems HealthCare and CropScience would like to address. In this way we are continually expanding the platform’s biocatalyst collection with the aim of reducing the time required to find the necessary enzymatic activity,” explains Dr. André Pütz, Biochemistry & Biocatalysis at Bayer Technology Services. Once the experts at Bayer Technology Services, Bayer HealthCare and Bayer CropScience have found, isolated and characterized suitable enzymes ­after screening the new collection, Coco’s team starts up the optimization machinery to further perfect the biocatalysts’ properties. Coupled with a wealth of know-how and innovative approaches, this process ultimately results in a customized biocatalyst that is suitable for industrial use. But even during the often time-consuming development cycles, both smaller and larger breakthroughs often occur.

A Visit to the Biological Reaction Accelerators

Automated Drug Discovery

One of the techniques employed by modern researchers in  the process of protein engineering is high-throughput screening. In this process, robots test many tens of thousands of potentially improved protein variants within a very short period of time.

Antibody production line: the glass flask containing a cell culture medium that Bayer HealthCare employee Astrid Rueter is holding in her hands turns human cells into miniature production plants, capable of growing more than a gram of a specific therapeutic antibody in just 6 days.
Treasure hunters: Alexander Korseska and Nina Habrich (left to right) use robots to test up to 80,000 protein variants every day.
Enhanced production: to optimize production of the crop protection agent indaziflam, Dr. Mark Ford and his colleagues from Process Research and Development tested a number of different trial synthesis sequences in the lab, and ultimately transferred the process to large-scale production with the help of biotechnology.
Mass production: robot systems are used to produce proteins in large quantities.
Focus on proteins: antibody specialist Dr. Fred Aswad works on optimizing protein molecules.
High-tech biotech: Dr. Wayne Coco relies on the support of a fully automated robotic facility to develop innovative proteins.

New Enzymes Benefit Modern Society

“Thanks to the Nimbus platform, we were not only able to substantially reduce screening times. In addition, we have frequently had quick wins. The knowledge compiled in the project to date has already been put into practice in a few cases. This is only possible because we are now well networked internally and nurture a lively scientific discourse,” explains Ford. Bayer’s scientists gain additional knowledge with every project cycle, every enzyme and every customized biocatalyst. And ultimately, it is doctors, patients, farmers and consumers who will benefit from this wealth of knowledge.


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