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Cambridge Healthtech Institute’s 3rd Annual

Microbial Production

January 17-18, 2019

 

Microbial-based expression systems offer significant advantages over other hosts by offering faster development times, greater yields, and lower production costs, particularly in E. coli. However, limitations around expression, glycosylation and central metabolic pathways poses significant challenges. 

Cambridge Healthtech Institute’s 3rd Annual Microbial Production conference examines the latest developments in microbial-based production – from strain development to metabolic engineering, assembly to scale-up, process development to analytics. Particular focus is with particular focus on the role of E. coli for biotherapeutics, novel products and other industrial applications.

Final Agenda

THURSDAY, JANUARY 17

7:45 am Registration and Morning Coffee

Microbial Expression of Biotherapeutics

8:10 Organizer’s Welcome Remarks

Daniel Barry, Senior Conference Director, Cambridge Healthtech Institute

8:15 Chairperson’s Opening Remarks

Danielle Tullman-Ercek, PhD, Associate Professor, Department of Chemical and Biological Engineering, Northwestern University


KEYNOTE PRESENTATION

8:20 Bacterial Cell-Based and Cell-Free Systems for Biosynthesis of Complex Glycans and Glycoconjugates

Matthew P. DeLisa, PhD, William L. Lewis Professor, Chemical & Biomolecular Engineering, Cornell University

Our group has harnessed natural biological pathways and engineered synthetic designer pathways in bacteria for making complex glycans and conjugating these to lipids and proteins. In this talk, I will discuss how these efforts have resulted in the transformation of bacteria and their cell-free extracts into robust platforms for scalable, bottom-up production of complex glycoconjugates by design.

9:00 Shaping Escherichia coli for Recombinant Protein Production

De_Gier_Jan_WilliamJan-Willem de Gier, PhD, Associate Professor, Department of Biochemistry and Biophysics, Stockholm University

My laboratory has been using both evolutionary and engineering approaches to shape E. coli for the production of recombinant proteins. In my talk, I will focus on how we have been engineering E. coli for the production of recombinant proteins in the periplasm as well as the development of vaccines.


9:30 Presentation to be Announced

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

Host Engineering and Strain Development in E. coli

11:00 Parallel Approach to Membrane Protein Production

Lee_JonasJonas Lee, PhD, Scientist, Amgen

Membrane proteins are vital therapeutic targets. Despite this, production of these critical reagents relies mostly on reproducing published results in painstaking ways. We developed an efficient systematic approach to screen multiple expression systems and different protein formulation to efficiently produce membrane protein reagents.

11:30 Optimizing Expression of an Antibody Fab Fragment in Escherichia coli with Non-Native Amino Acid (NNAA) Incorporated by Plasmid and Strain Engineering

Harun Rashid, PhD, Senior Principal Scientist, Molecular Technology, Ambrx

In this study, expression of a ‘difficult-to-express’ antibody Fab fragment with a NNAA inserted was systematically optimized by expression vector & strain engineering. Among the various genetic elements on expression vector tested, only the DNA coding sequence, periplasmic chaperone, Fab heavy chain (HC) carboxy-terminal extension and the presence of partition locus parB were beneficial. These four components were then put together into a single expression vector that resulted in significant improvement in Fab titer over the starting strain.

12:00 pm Session Break

12:10 Luncheon Presentation: Leveraging Platform Approaches and High-Throughput Tools to Expedite Process Development in a Multi-Product Microbial Manufacturing Environment

Nigel Shipston, PhD, Director, Program Design, FUJIFILM Diosynth Biotechnologies

1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing

2:15 Chairperson’s Remarks

Nigel Shipston, PhD, Director of Program Design, FUJIFILM Diosynth Biotechnologies

2:20 Robust Protein Production and Secretion in Bacteria via the Type III Secretion System

Tullman_Ercek_DanielleDanielle Tullman-Ercek, PhD, Associate Professor, Department of Chemical and Biological Engineering, Northwestern University

Bacteria are receiving renewed interest as protein production hosts because of their fast growth and tractability. The Salmonella enterica Type III Secretion System secretes non-native proteins at product titers of up to 400 mg/L in rich media, but is highly sensitive to environmental and growth conditions and therefore not robust. To make this system commercially relevant, we optimized media components and bioreactor conditions and engineered the strain.

2:50 Development of a Scalable Platform for Protease Triggered Immuno-Oncologic Activators

Ernst_UlrichUlrich Ernst, PhD, COO and Senior Vice President, Technical Operations at Amunix

The design of ProTIA molecules represents a technical enhancement of bispecific scFv therapeutic formats, with the benefits of significantly improved circulatory half-life, enhanced tumor-targeting and safety profiles. To enable clinical application of its pipeline of ProTIA therapeutics, Amunix has applied its extensive experience with XTENylation of proteins, thus, yielding a scalable, platform process for efficient production of these new therapeutic compounds.

3:20 Sponsored Presentation (Opportunity Available)

3:35 Networking Refreshment Break

4:00 E. coli Glycosylation Platform for Producing Bioconjugate Vaccines

Lizak_CChristian Lizak, PhD, Group Leader Biochemistry, Research Department, LimmaTech Biologics AG

The discovery of an N-linked protein glycosylation system in Campylobacter jejuni allowed its reconstitution in Escherichia coli. LimmaTech Biologics exploits this system to generate bioconjugate vaccines containing surface glycan structures of pathogenic bacteria. This innovative approach simplifies the production of conjugate vaccines substantially and has been used to generate multivalent bioconjugates against pathogens like Shigella, Streptococcus, E. coli and Staphylococcus, some of which have been successfully tested in clinical studies.

4:30 Glycoengineering Next Generation Conjugate Vaccines with Novel Oligosaccharyltransferases

Harding_ChristianChristian Harding, PhD, CSO, VaxNewMo

Glyco-conjugate vaccines, consisting of a polysaccharide attached to a carrier protein, are excellent immunogens manufactured using labor-intensive chemical crosslinking steps. As an innovative alternative, VaxNewMo utilizes a glycoengineering strategy to generate “bioconjugates” in Escherichia coli. Key to this process is a conjugating enzyme, which attaches a polysaccharide to a protein.

5:00 Bryotechnology: High Quality Complex Proteins from Moss-Based Expression

Schaaf_AndreasAndreas Schaaf, PhD, CSO, Greenovation

BryoTechnology, i.e., moss-based production of biopharmaceuticals, has evolved into a GMP manufacturing technology with products already in clinical development. Whilst leveraging the mosses advantages, comparability to mammalian cell-based technologies was a priority in process development. Today’s moss process relies on latest single use technologies and follows the established routines of mammalian cell-based production. Thus, moss-based production fits easily into existing cleanroom environments and offers rapid changeover and flexible configuration.

5:30 Close of Day

FRIDAY, JANUARY 18

8:00 am Registration

8:00 BuzZ Sessions with Continental Breakfast

Protein therapeutics is a fast-growing global market. As the science improves, so does the complexity of the R&D organization. Ensuring product quality plus speed to market requires insights from stakeholders working across the stages of protein science R&D. Join experts representing this PepTalk pipeline, peers, and colleagues for an interactive roundtable discussion. Topics include highlights from the week’s presentations, new technologies and strategies, challenges, and future trends.


Moderator: Suresh Kumar Thallapuranam, PhD, Professor, Department of Chemistry & Biochemistry, University of Arkansas

 

Bioprocessing of Microbial-Based Products

9:00 Chairperson’s Remarks

Suresh Kumar Thallapuranam, PhD, Professor, Department of Chemistry & Biochemistry, University of Arkansas

9:05 Integrated Process Development: Overcoming Developability Challenges

Klima_GeorgGeorg Klima, Dipl. Ing., Executive Director, Process Science, Boehringer Ingelheim RCV GmbH & Co. KG

Novel biotherapeutic formats pose unique development challenges. Strategies for successful development need to holistically consider all aspects of biopharmaceutical processes such as expression strategies, novel unit operations, automated high-throughput process development, as well as scale-up and transfer from bench to large-scale manufacturing. We present our holistic approach based on a HTPD toolbox to lever the complexity of manufacturing development for non-platform biotherapeutics. Integration of the whole process is also discussed.

9:35 Novel Affinity Tags for Large Scale Production and Purification of Recombinant Proteins

Suresh Kumar Thallapuranam, PhD, Professor, Department of Chemistry & Biochemistry, University of Arkansas

Synthetic Biology and Cell-Free Systems

10:05 A Semi-Synthetic Organism That Stores and Retrieves Increased Genetic Information

Romesberg_FloydFloyd Romesberg, PhD, Professor, Chemistry, The Scripps Research Institute

We have examined a large number of different unnatural nucleotides bearing mainly hydrophobic nucleobase analogs that pair based on packing and hydrophobic interactions rather than H-bonding. More recently, we have engineered E. coli to import the requisite unnatural triphosphates and shown that DNA containing the unnatural base pair is efficiently replicated, transcribed, and translated within the cell, resulting in the first semi-synthetic organism that stores and retreives increased information.

10:35 Networking Coffee Break

11:00 Building a Cell-Free RNA Production Platform

Himanshu Dhamankar, PhD, Senior Scientist, Pathway & Process Development, GreenLight Biosciences Inc.

Availability of low-cost RNA products can unlock numerous applications spanning the agricultural and biopharmaceutical spaces. GreenLight Biosciences has developed a scalable and cost-effective RNA production platform that employs a proprietary one-pot cell-free reaction to synthesize nucleotide triphosphates from an inexpensive nucleotide source, that are then polymerized into desired RNA products via transcription from an engineered DNA template. The presentation will feature building of the platform and on-going efforts towards improvements.

11:30 Rapid and Scalable Characterization of CRISPR Technologies Using an E. coli Cell-Free Transcription-Translation System

Noireaux_VincentVincent Noireaux, PhD, Associate Professor, Synthetic Biology, Biological Physics, University of Minnesota

CRISPR-Cas systems offer versatile technologies for genome engineering, yet their implementation has been outpaced by ongoing discoveries of new Cas nucleases and anti-CRISPR proteins. Here, we present the use of E. coli cell-free transcription-translation (TXTL) systems to vastly improve the speed and scalability of CRISPR characterization and validation. TXTL can express active CRISPR machinery from added plasmids and linear DNA, and TXTL can output quantitative dynamics of DNA cleavage and gene repression – all without protein purification or live cells.

12:00 pm Conference Wrap-Up

Suresh Kumar Thallapuranam, PhD, Professor, Department of Chemistry & Biochemistry, University of Arkansas

12:30 Close of Conference

* The program is subject to change without notice, due to unforeseen reason.

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