The Chain: Protein Engineering Podcast

Nancy Sajjadi joins The Chain to share her quality control knowledge and experience of adopting a quality-by-design approach for assays. We discuss how the focus of her QC work has changed through the years, and what kind of challenges she foresees as the cell and gene therapy fields move forward. Ms. Sajjadi talks about consulting with clients who are developing cutting edge therapies and explains her approach of creating a “culture of quality” within scientific organizations to lead to more successful outcomes.   Nancy Sajjadi, Independent Quality ConsultantNancy Sajjadi, M.Sc. is an independent quality consultant with over 30 years of experience in biopharmaceutical product development. She began her career as a bench scientist doing malaria vaccine research before turning to development of cell and gene using therapy retroviral vectors for infectious disease, cancer, and cell therapy applications. Her responsibilities there included research, development, and quality control. She left her position as Director of QC at Chiron Technologies Center for Gene Therapy, in 2000 and to start a consulting business.   She has provided services to biopharmaceutical companies, contract laboratories, non-profit organizations, universities, and US government agencies. She has assisted clients in the development, implementation, and improvement of quality programs for a range of biopharmaceutical products in early phase development.  She also has provided technical expertise in assay development, qualification, and validation. Ms. Sajjadi has authored several articles pertaining to bioassays and viral gene therapy, has served on 5 advisory panels for the United States Pharmacopeia (USP) and teaches introductory courses in bioassay design, development, and validation for non-statisticians. 

In this episode, Dr. Willem Overwijk returns for a conversation with Dr. Éric Vivier. Dr. Vivier is a professor of immunology at Aix-Marseille and a hospital practitioner at Marseille Public University Hospital. Éric Vivier is also the Chief Scientific Officer at Innate Pharma, a clinical-stage biotech company that creates novel antibodies that activate the immune system to treat patients with cancer. They discuss Dr. Vivier’s scientific background, the importance and the potential of Natural Killer cells, and the next wave of immunotherapy.

This episode of The Chain features a live panel discussion moderated by Erica Ollmann Saphire, PhD of La Jolla Institute for Immunology. Expert panelists from academia and government assess the COVID-19 antibody and vaccine development thus far, including what did and did not go well during the pandemic. They also look towards the future and the role mRNA vaccines may play for diseases like influenza, what we learned about the United States’ ability to manufacture during surge production, and what infrastructure is still needed to fight both the current crisis and future outbreaks. Erica Ollmann Saphire, PhD, Professor, La Jolla Institute for ImmunologyPeter Hotez, MD, PhD, FASTMH, FAAP, Dean, National School of Tropical Medicine; Professor, Departments of Pediatrics, Molecular Virology & Microbiology; Co-Head, Section of Pediatric Tropical Medicine; Health Policy Scholar, Baylor College of MedicineLakshmi Krishnan, PhD, Vice-President, Life Sciences, National Research Council Canada, Government of CanadaPeter W. Marks, MD, PhD, Director, FDA CBER

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.