The Chain: Protein Engineering Podcast

The Center for Structural Genomics of Infectious Diseases at Northwestern University was prepared for COVID-19 long before the United States economy shut down. Now over a year since COVID-19 was first recorded in the U.S., co-director Dr. Karla Satchell speaks with The Chain about the role of structural genomics in preparing for disease outbreak and response.Karla Satchell, PhD, Professor, Microbiology; Principal Investigator and Co-Director, Center for Structural Genomics of Infectious Diseases, Northwestern UniversityDr. Karla Satchell is a Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine since 2000. She is also the Principal Investigator for the NIAID-funded Center for Structural Genomics of Infectious Diseases, a multi-site center in high-throughput structure determination for microbial pathogens. In 2020, the Center dedicated significant resources to structural biology of SARS-CoV-2, including efforts to provide structural biology data to support development of novel drugs, vaccines, and therapeutics. Across all areas of research, she has published more than 100 research articles. She has also been elected as a Fellow for the American Academy of Microbiology and the American Association for the Advancement of Science. 

Linoleic acid is an essential free fatty acid in the human body and its metabolic pathway is central to immune regulation and inflammation – which are also key symptoms in COVID-19. Using cryo-electron microscopy, Christine Toelzer’s research identified linoleic acid bound to a hydrophobic pocket of the SARS-CoV-2 glycoprotein. Christine shares her thoughts on how these findings will contribute to the fight against COVID-19 and how her lab work has been altered by the pandemic. Christine also discusses the future of other young scientists coming up in the protein science space. Christine Toelzer is currently a Research Associate at the University of Bristol. After a M.Sc. in biology and an additional M.Sc. in physics she continued with PhD work in biochemistry at the University of Cologne. Her research has always focused on structure function relationships, starting with structure determination of biotechnologically important proteins by x-ray crystallography, magnetic structure determination of inorganic compounds by neutron diffraction and recently using electron cryo-microscopy to obtain the structure of large protein complexes involved in transcription and diseases. In the last year (2020) she started coronavirus related work to contribute to the global effort aimed at better understanding the virus and uncover its potential weaknesses.About the Young Scientist Keynote Award:This recognition honors a young scientist from the international protein science community who has contributed to scientific advancement and innovation in this field. Nominations were solicited from across academic and industry research groups in the fall of 2020, and the finalists were determined through the votes and input of our 15-person advisory panel.

In this episode we talk with Dennis Karthaus of IBA Lifesciences about his early science interests and pursing his PhD. His passion for marine biology eventually led him on a path to study biotechnology, where he now focuses on protein expression and purification. Specifically, tag-based purification that can help researchers increase lab productivity. But, as our guest explains, scientists should consider their specific bottlenecks and applications for the protein of interest, to determine if a tag is right for them. 

In a roundtable discussion, three experts bring perspectives on different methods for generating antibodies, including generating antibodies from naive libraries, patients, and immunizations. They discuss how the COVID-19 pandemic has highlighted the advantages of refocusing on infectious disease research. As well as the importance of having ready immune libraries and immunized mice, plus other approaches, ahead of any future infectious disease outbreak.  

The purification requirements in the biopharmaceutical industry will be even more demanding in the coming years due to increased awareness of product-related impurities like oligomers, variants, positional isomers, and glycoforms. These impurities need to be separated from the final product. Dr. Raja Ghosh’s work focuses on the design and development of efficient chromatography devices that combine high-speed with high-resolution in separation. He speaks with Dr. David Wood of the Ohio State University about how the chromatography devices he is developing address these challenges.  

On this episode of The Chain, Dr. Willem Overwijk shares his personal experience of his recent transition from academia to industry, and the differences between the two. Dr. Overwijk moved to industry, in part, to follow his research interest in a specific molecule that he had been working on since graduate studies: interleukin-2. Thanks to advances in protein engineering, this once ultra-potent molecule now can be administered with lower toxicity while still being an effective cancer therapy. We discuss IL-2, plus the exciting future of protein engineering in immuno-oncology. 

Dr. Dimiter Dimitrov, Director of the Center for Antibody Therapeutics at the University of Pittsburgh, sits down with The Chain to discuss his research and its relevance to the current pandemic. His work focuses on human VH domains, which in contrast to the animal antibody domains, like llama and shark, may have lower probability of immunogenicity. Dr. Dimitrov helps develop several such domains, most recently against SARS2, and one of which that is in production for evaluation in human clinical trials. Beyond COVID-19, Dr. Dimitrov explains that clinical trials for various cancer-related proteins and HIV are also underway, showing the vast potential for domains both for industry growth and life-saving therapies. 

Dan Chen returns for the Science Commune segment and speaks with Dr. Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research (CBER). Dr. Marks reflects on his fortuitous path from academia to industry to government, plus the differences between each area. Dr. Marks explains the research and regulatory role of CBER, especially as it pertains to the latest cell therapies. And finally, the two discuss the impressive speed of COVID-19 vaccine science breakthroughs and regulatory approval. 

Christian Klein is a longtime and key member of the protein and antibody community. In this episode, he speaks with Executive Conference Producer, Christina Lingham, on how the field has changed since their first collaboration. Dr. Klein offers an overview of the latest applications of bispecific antibodies, including the latest progress of clinical trials by Roche and others. He also explains how the PD1-X molecule is unique and can increase specificity of therapeutics even more. 

There are no bad ideas in developing bioanalytical testing, says Jim McNally, CSO of BioAgilytix. Not all ideas will work, of course. But he has found that it is the outside-the-box ideas that often turn out to be the solution in challenging assay work. Dr. McNally speaks with The Chain about his background in bioanalytical testing and supporting clinical trials, the exciting future of cell and gene therapies, and the importance of setting precedent in bioanalysis of these new, life-saving therapies. It is an exciting time for gene therapy especially, and Dr. McNally shares how new immunogenicity data is getting us closer to bringing this therapy to more people.