Protein Expression System Engineering

CHI’s 6th Annual Protein Expression System Engineering conference examines the functioning of the cellular machinery harnessed during protein biosynthesis, and how to engineer hosts to efficiently express a protein of interest. The intricate steps required to achieve properly folded protein will be discussed, including verification and sequence analysis of the gene, codon optimization, vector construction, selecting and optimizing a clone, and selecting a host system. In addition, engineering host cells to sustain expression for longer time periods will be discussed, along with overcoming cellular stress response to produce and secrete functionally active recombinant proteins.

Thursday, September 3

HARNESSING OMICS

12:45 pm

Product Quality Control Strategy Development for Non-mAb Complex Modalities by Using Combinatorial Cell Engineering and OMICS Screening Tools

Amit Kumar, PhD, Senior Scientist, Merck Research Labs

To improve understanding and increase options in developing a successful production cell line with desired product quality profile, it is important to develop diversified CHO host lineages with differences in cell growth and protein production in responding to medium and process conditions. In addition, developing predictive OMICS tools and integrating into quality control strategy are highly useful in selecting highly productive recombinant cell lines with the desired protein quality profile.

1:25 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Stefan R. Schmidt, MBA, PhD, COO & Head, Operations, BioAtrium AG
Panelist:
Amit Kumar, PhD, Senior Scientist, Merck Research Labs
1:45 pm Session Break
2:10 pm Refresh Break - View our Virtual Exhibit Hall

CELL-FREE STRATEGIES

2:30 pm KEYNOTE PRESENTATION:

New Methods for Cell-Free Presentation of Proteins for Functional Analysis

Joshua LaBaer, PhD, Executive Director, Arizona State University Biodesign Institute

Self-assembling protein microarrays made through cell-free synthesis have been used widely to study protein interactions with drugs and other proteins, to search for enzyme substrates, and to find disease biomarkers, including some that are in clinical use for the detection of cancer in blood. Recent methodological advances now enable new types of studies including highly multiplexed analysis, testing the effects of post-translational changes on protein interactions and providing highly quantitative readouts with significantly reduced background noise.

2:50 pm

Cell-Free Based Approach for Genetic Encoding of Unnatural Chemistries

Zhenling Cui, PhD, CTCB, Research Associate, Science and Engineering, Chemistry, Physics, Mechanical Engineering, Energy and Process Engineering, Queensland University of Technology (QUT)

Genetic code expansion holds the promise to revolutionize the life science and biomedicine through expanding macromolecular chemical diversity outside the natural space. We developed an engineered Escherichia coli cell-free system which allows rapid sequestration of selected native tRNA isoacceptors and subsequent reassignment of the liberated sense codons to unnatural amino acids. This represents a powerful tool for numerous practical applications including production of constrained peptides, antibody-drug conjugates and novel enzymes.

3:10 pm

Co-Translational Insertion of Challenging Membrane Proteins into Nanomembranes by Cell-Free Expression

Julija Mezhyrova, MSc, Scientist, Institute of Biophysical Chemistry, Goethe University

Cell-free expression systems became key tools for the production of membrane proteins and other challenging targets. We have developed protocols to insert membrane proteins already co-translationally into supplied nanomembranes of defined composition. The generated protein/nanoparticles are suitable for biochemical and structural studies and contacts with detergents or other artificial environments are avoided. The strategy is exemplified with membrane-inserted phage toxins currently being explored as potential inhibitors of bacterial cell-wall formation.

3:30 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Stefan R. Schmidt, MBA, PhD, COO & Head, Operations, BioAtrium AG
Panelists:
Joshua LaBaer, PhD, Executive Director, Arizona State University Biodesign Institute
Zhenling Cui, PhD, CTCB, Research Associate, Science and Engineering, Chemistry, Physics, Mechanical Engineering, Energy and Process Engineering, Queensland University of Technology (QUT)
Julija Mezhyrova, MSc, Scientist, Institute of Biophysical Chemistry, Goethe University
3:50 pm Close of Day

Friday, September 4

BREAKTHROUGH ADVANCES

9:05 am

A General Approach to in vitro Protein Folding Using Nanoencapsulation

Chester Drum, MD, PhD, Assistant Professor, Translational Innovation, National University of Singapore

A novel nanoparticle can encapsulate, fold and release proteins of a wide range of sizes, charges, and disulfide content to produce improved yields and improved specific activity. Our index manuscript (Nature Communications | 8: 1442) described the concept and we have a much larger manuscript under review now which we fully expect to be published this year.

9:25 am

Elevating the Science via a Novel Pipetting Algorithm, 3D-Printing Technology and a Next-Generation Advanced Control Machine

Idris Mustafa, CEO & Chief Engineer, Idris Dot Solutions LLC

TipSort technology (an advanced, in-house robot pipetting algorithm) optimizes pipetting throughout a dynamic 96-position plate or tip tray. In-house CAD design married to 3D-printing fuels the crafting of custom lab inventions, spawning innovation and saving dollars. A fully-loaded Hamilton Vantage Robot enhanced with custom configuration/integrations and a built-in machine learning driven scheduler will support the future of small-scale protein expression analysis in the laboratory.

Volker Sandig, Chief Scientific Officer, ProBioGen AG

ProBioGen's travel equipment for the shortest journey to even higher mountains of cell productivity (with a high elevation base camp at pool stage)

In this talk we will assess consecutive advancements of the transposon system: genome targeting, activity and template recognition and show how this optimized system combined with the a refined ALS CellCelector platform affects the cell line development workflow and its outcome for antibodies, proteins and viral vectors.

10:10 am LIVE Q&A:

Session Wrap-Up

Panel Moderator:
William C.W. Chen, MD, PhD, Research Scientist, Massachusetts Institute of Technology
Panelists:
Chester Drum, MD, PhD, Assistant Professor, Translational Innovation, National University of Singapore
Idris Mustafa, CEO & Chief Engineer, Idris Dot Solutions LLC
Volker Sandig, Chief Scientific Officer, ProBioGen AG
10:30 am Speed Networking Coffee Break - View our Virtual Exhibit Hall

APPLYING NEXT-GEN TECHNOLOGIES

10:50 am

The Predictive Cellular and Protein Effects of Glycoengineering

Nathan Lewis, PhD, Associate Professor, Pediatrics, University of California, San Diego (UCSD)

With most top blockbuster drugs therapeutics being glycoproteins, there is a growing interest in engineering their glycan structures for improved safety, efficacy, and manufacturing. Using our systems biology approaches, we can predict the modifications needed to effectively glycoengineer proteins. We further have explored the more global impacts glycoengineering has on the host cell, thus helping to define the design space of CHO-produced glycoproteins.

11:10 am

Codon and Codon-Pair Usage Tables (CoCoPUTs): Facilitating Genetic Variation Analyses and Recombinant Gene Design

Chava Kimchi-Sarfaty, PhD, Deputy Associate Director for Research, Office of Tissues and Advanced Therapies, CBER, FDA

A novel public resource that presents all codon usage, codon-pair usage and human tissue specific codon usage and codon-pair usage will be discussed. Examples of investigation areas which could greatly benefit from this resource will be provided, such as biotherapeutic development, tissue-specific genetic engineering and genetic disease prediction.

Meredith Jackrel, PhD, Assistant Professor, Department of Chemistry, Washington University in St. Louis

There are no therapies that reverse the proteotoxic misfolding events that underpin neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Hsp104, a hexameric AAA+ protein from yeast, solubilizes disordered aggregates and amyloid but has only limited activity against human neurodegenerative disease proteins. Here I will describe approaches we have employed to re-engineer Hsp104. The engineered variants can dissolve aggregates, restore protein localization, suppress proteotoxicity, and attenuate dopaminergic neurodegeneration in animal models.

11:55 am LIVE Q&A:

Session Wrap-Up

Panel Moderator:
William C.W. Chen, MD, PhD, Research Scientist, Massachusetts Institute of Technology
Panelists:
Nathan Lewis, PhD, Associate Professor, Pediatrics, University of California, San Diego (UCSD)
Chava Kimchi-Sarfaty, PhD, Deputy Associate Director for Research, Office of Tissues and Advanced Therapies, CBER, FDA
Meredith Jackrel, PhD, Assistant Professor, Department of Chemistry, Washington University in St. Louis

ADVANCING MAMMALIAN CELL ENGINEERING

12:15 pm Lunch Break - View Our Virtual Exhibit Hall
12:35 pm

Advanced Synthetic Biology Tools to Accelerate Mammalian Protein Expression System Engineering

William C.W. Chen, MD, PhD, Research Scientist, Massachusetts Institute of Technology

Conventional mammalian protein expression strategies using transient expression or random genome integration with gene of interest, followed by high-throughput colony screening and expansion, are laborious and/or time-consuming. To address those issues, we have developed a series of synthetic biology toolkits to transform mammalian protein expression system engineering. Our powerful platform technologies are versatile and can be adapted to different mammalian cell types and biomanufacturing settings to optimize complex therapeutic protein production.

12:55 pm

Exploitation of a Ribosomal Protein Mutation to Enhance Recombinant Protein Production

Kim De Keersmaecker, PhD, Research Professor, Oncology – Laboratory for Disease Mechanisms in Cancer, Katholieke Universiteit Leuven

A mutation in a ribosomal protein that we discovered in cancer cells enhances the levels of ribosomal protein translation and its fidelity, and reduces cellular proteasome activity in lymphoid cell models. To validate these findings in mammalian cell lines that are commonly used in the recombinant protein production industry, we engineered the ribosomal mutation into CHO and HEK293 cells. A 69-155% increase in production of 3 recombinant proteins was confirmed in HEK293 cells.

1:15 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Amr Ali, PhD, Sr. Scientist II, Protein Analytics, Science & Technology Biologics, AbbVie
Panelists:
William C.W. Chen, MD, PhD, Research Scientist, Massachusetts Institute of Technology
Kim De Keersmaecker, PhD, Research Professor, Oncology – Laboratory for Disease Mechanisms in Cancer, Katholieke Universiteit Leuven
1:30 pm Close of Summit





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