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- 合成及系统工程 -

The complexity of biotherapeutics and the increasing demands of “faster, better, less expensive” resonate with recombinant protein expression and production researchers. To meet these demands, protein scientists are exploring new engineering tools. However, many variables still must be considered during the engineering process, including verification and sequence analysis of the gene or protein of interest, codon optimisation, vector construction and clone/host selection. Ultimately, as with any new system, these tools must be weighed against traditional expression and production strategies to achieve the desired quantity and quality.

The Systems Engineering and Synthetic Biology conference applies effective engineering strategies for protein expression and production research leading to functional protein products. Learn from seasoned, savvy researchers as they share their real-world experiences, applications and results.


Final Agenda

MONDAY 12 NOVEMBER | 09:00 - 12:00 | MORNING

Recommended Short Course*

SC1: Transient Protein Expression: A Key Tool to Enable Rapid Protein Engineering

Richard Altman, MS, Scientist, Protein Technologies, Amgen

Henry C. Chiou, PhD, Associate Director, Cell Biology, Life Science Solutions, Thermo Fisher Scientific

Dominic Esposito, PhD, Director, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research

This short course introduces both the fundamental concepts and technologies needed to establish transient protein production in mammalian cells, which has become an essential tool to enable rapid protein engineering. Transient expression allows for the rapid generation, purification and characterization of milligram-to-gram quantities of secreted or intracellular recombinant proteins for therapeutic, functional and structural studies. The course combines instruction and case studies in an interactive environment.

*Separate registration required.

MONDAY 12 NOVEMBER

12:00 Conference Registration

ENGINEERING EFFICIENT EXPRESSION

13:30 Organizer’s Welcome

Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute

13:35 Chairperson’s Opening Remarks

Dominic Esposito, PhD, Director, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research

13:45 Expanding the Synthetic Biology Toolbox for CHO Cell Factories

Helene Faustrup Kildegaard, PhD, Senior Researcher & Co-Principal Investigator, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

Chinese hamster ovary (CHO) cells are widely used in the biopharmaceutical industry as a host for the production of complex therapeutic proteins. Thus, efficient synthetic biology tools to improve CHO cell factories are of great interest. Here, our latest development of these tools will be demonstrated. Together with high-throughput technologies and systems biology approaches, synthetic biology can pave the way for accelerated generation of desirable CHO cell factories with predicted culture performance.

14:15 CRISPR-Cas Implementation and Novel Expression Tools for Non-Conventional Yeasts

Thomas Vogl, PhD, Researcher, Department of Computer Science and Applied Mathematics & Department of Molecular Cell Biology, Weizmann Institute of Science

The setup of efficient CRISPR/Cas systems and the toolbox of advanced CRISPR-related applications will be illustrated by the example of the methylotrophic yeast Pichia pastoris (doi:10.1016/j.biotechadv.2018.01.006). Furthermore, synthetic biology and metabolic engineering experiments frequently require the fine-tuning of gene expression to balance and optimize protein levels of regulators or metabolic enzymes. Here also novel strategies for the transcriptional fine-tuning of gene co-expression will be presented.

14:45 Engineering the Trichoplusia ni Insect Cell Line Tni-FNL to Improve Recombinant Protein Production

Dominic Esposito, PhD, Director, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research

Tni-FNL is a fully sequenced insect cell line which is capable of outproducing many other T. ni cell lines in recombinant protein production. We describe ongoing systems biology efforts to better understand how this cell line functions and to improve characteristics related to higher protein yield and quality.

15:15 Sponsored Presentation (Opportunity Available)

15:45 Networking Refreshment Break



PLENARY KEYNOTE SESSION

16:15 Moderator’s Opening Remarks

Janine Schuurman, PhD, Corporate Vice President, Research & Innovation, Genmab BV

 

 

 

 

16:20 Bicycles and Bicycle Drug Conjugates

Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co-Founder and Director, Bicycle Therapeutics

Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential in many indications, including oncology, where Bicycles’ unique properties have been used to develop Bicycle Drug Conjugates™ (BDCs); a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018.

17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ

Andreas G. Plückthun, PhD, Professor and Director, Department of Biochemistry, University of Zürich

Cancer will have to be fought with cocktails of therapeutics acting locally, which may have to include therapeutic antibodies against receptors, checkpoint inhibitors, as well as cytokines to modify the tumor microenvironment. We have recently developed a technology of using non-replicative adenovirus carrying no viral genes, engineered to target desired cells and also to be shielded from the immune response, as a vehicle for simultaneous delivery of multiple genes of therapeutic proteins, produced and secreted by the infected cells.

18:20 Welcome Reception in the Exhibit Hall with Poster Viewing

19:30 End of Day

TUESDAY 13 NOVEMBER

07:45 Registration and Morning Coffee

CELL-FREE SYSTEMS

08:30 Chairperson’s Remarks

Fernando López-Gallego, PhD, ARAID Tenured Scientist, Institute of Synthetic Chemistry, University of Zaragoza

08:35 Cloning-Free Template DNA Preparation for a Wheat Germ Cell-Free System with Short 3’-UTR

Yasuomi Tada, PhD, Professor, Center for Gene Research, Nagoya University

Wheat germ cell-free protein synthesis (CFPS) systems are highly applicable for proteomics but require laborious and time-consuming cloning procedures. We developed a novel, effective short 3’-UTR sequence that facilitates in vitro translation. The short 3’-UTR enables the cloning-free generation of various transcription templates from the same plasmid, including fusion proteins with N- or C-terminal tags, and truncated proteins. Thus, our method provides a versatile platform for preparing DNA templates.

09:05 Expanding One-Pot Cell-Free Protein Synthesis and Immobilization for On-Demand Manufacturing of Biomaterials

Fernando López-Gallego, PhD, ARAID Tenured Scientist, Institute of Synthetic Chemistry, University of Zaragoza

Fabrication of biomaterials containing protein-based biomolecules requires the expression and purification of proteins followed by the immobilization process. An emerging alternative is the cell-free protein synthesis (CFPS) in solution. In this work, we propose the fabrication of protein-based biomaterials by coupling in vitro protein synthesis and immobilization in the same pot. To this aim, we have expanded the toolbox of peptide-tags to selectively immobilize proteins on different solid materials.

09:35 Problem-Solving Breakout Discussions

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

11:15 Cell-Free Protein Synthesis from Resting versus Ultra-Fast Growing Cells: Findings from Systems Biology

Martin Siemann-Herzberg, PhD, Institute of Biochemical Engineering, University of Stuttgart

In vitro protein synthesis allows rapid expression of proteins without the need to maintain a viable cell. Nevertheless, its effectivity depends on the activity of the former living cell. Consequently, standard in vitro systems are generated from fast-growing cells, premising most-active translational fidelity. Based on systems biology attempts, we examined the integrity of the in vitro protein synthesis machinery, e.g., generated from ultra-fast and non-growing cells.

11:45 Minimal Cell: Cell-Free Protein Synthesis in Micro-Compartments

Lei Kai, PhD, Group Leader, Department of Cellular and Molecular Biophysics, Max Planck Institute of Biochemistry

The construction of a minimal cell that exhibits the essential characteristics of life is a great challenge in the field of synthetic biology. Assembling a minimal cell requires multidisciplinary expertise from physics, chemistry and biology. Advances and developments of new methods and techniques, i.e., cell-free protein synthesis as well as microfabrication, showed great potential to resolve challenges and to accelerate the development of minimal cells.

12:15 Sponsored Presentation (Opportunity Available)

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:45 Dessert Break in the Exhibit Hall with Poster Viewing

ENGINEERING SYSTEMS-SCALE STRATEGIES

14:15 Chairperson’s Remarks

Arnaud Poterszman, PhD, Research Director, Integrated Structural Biology, IGBMC (CNRS/INSERM/UdS)

14:20 Design of Intracellular Inhibitors – A Platform for Target Validation and Drug Development

Andreas Ernst, PhD, Group Leader, Institute of Clinical Pharmacology, Goethe University Frankfurt

Targeting protein-protein interaction for therapeutic benefit represents one of the great challenges in the development of small molecule drugs. To address this problem, we have combined the design of intracellular inhibitors based on alternative protein scaffolds with the development of high-throughput small molecule screening assays. Additionally, the engineered intracellular affinity reagents allow characterization and validation of new intracellular drug targets.

14:50 Top-Down and Bottom-Up Strategies for Production of Human Multi-Protein Complexes

Arnaud Poterszman, PhD, Research Director, Integrated Structural Biology, IGBMC (CNRS/INSERM/UdS)

Macromolecular complexes are vital cornerstones of most, if not all, biological processes in cells. We illustrate how the CRISPR/Cas9 editing technology allows us to label and isolate native protein assemblies from their natural cellular environment and the potential of the baculovirus expression vector system for reconstitution of multi-subunit complexes. As model systems, we use transcription regulators such pTefb, nuclear receptors or the 10 subunits transcription factor TFIIH.

15:20 Engineering the Evolution of Bacteria for Protein Production

Morten Nørholm, PhD, Principal Investigator & Senior Scientist, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

Microorganisms have for centuries shown great capacity to produce useful materials. However, they are also naturally intolerant to dedicating all resources to a specialized metabolic task and inherently prone to evade stress and evolve new properties. We have explored natural and synthetic evolution of bacteria for production of pharmaceutical proteins and industrial enzymes.

15:50 Sponsored Presentation (Opportunity Available)

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing


17:00 KEYNOTE PRESENTATION: From Systems Biology to Systems Biologics

Sachdev Sidhu, PhD, Professor, Molecular Genetics, The Donnelly Centre, University of Toronto

We have established a platform to combine large-scale systems biology approaches with the discovery and development of new antibody drugs, and to develop efficient, systems-scale strategies to target intracellular signaling networks at the protein level with ubiquitin variants and other scaffolds. This efficient pipeline connects basic research to translational science in a new model for drug development, which we have termed “Systems Biologics”.

17:30 CLOSING PANEL DISCUSSION: Tools for Expanding the Protein Engineering and Production Toolbox

Moderator:

Tsafi Danieli, PhD, Director, BioGiv Excubator & Head, Protein Expression Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem

Panelists:

Richard Altman, MS, Scientist, Protein Technologies, Amgen

Nicola Burgess-Brown, PhD, Principal Investigator, Biotechnology, Structural Genomics Consortium (SGC), University of Oxford

Henry C. Chiou, PhD, Associate Director, Cell Biology, Life Science Solutions, Thermo Fisher Scientific

Dominic Esposito, PhD, Director, Protein Expression Laboratory, Frederick National Laboratory for Cancer Research

Mario Lebendiker, PhD, Head, Protein Purification Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem

Bjørn Voldborg, MSc, Director, CHO Cell Line Development, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

18:30 End of Systems Engineering and Synthetic Biology

* 活动内容有可能不事先告知作更动及调整。

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