"Engineering Life" symposium at the Swiss Embassy in London

13:35 - 14:05
Engineering Life with Molecular Systems
Thomas Ward, NCCR MSE & Department of Chemistry, University of Basel, Basel

This presentation will summarize the efforts of the thirty groups involved in the National Center of Competence “Molecular Systems Engineering”. I will first outline the general concept of Engineering Life with Molecular Systems and go on to present recent applications of our approach to i) mimic life-like features in artificial systems, and ii) complement cellular systems with molecular or cellular prosthetics The presentation will end with the future perspectives that Molecular Systems Engineering offer to address unmet medical challenges.

14:05 - 14:35
Rapid Discovery of High-Affinity Antibodies by Deep Screening
Philipp Holliger, MRC Laboratory of Molecular Biology, Cambridge

Therapeutic antibodies have had a transformative clinical impact notably in inflammatory diseases and cancer, but their development remains time-consuming as well as costly. I will present deep screening, an ultra-high-throughput approach leveraging the Illumina HiSeq platform for massively parallel sequencing, display, and rapid antigen-binding affinity and kinetics screening at the level up to 10⁹ individual antibody-antigen interactions. Deep screening enabled the rapid discovery of high-affinity antibodies such low-nanomolar nanobodies (VHH) from immunized-alpaca or yeast display-enriched VHH libraries and picomolar single-chain Fv (scFv) antibody leads directly from unselected, synthetic scFv repertoires in a three-day experiment. Deep screening generates large, internally-consistent genotype-phenotype (antibody-antigen binding / kinetics etc.) correlation datasets that can serve as training data for a language-model-enabled machine learning approach for the rapid in silico generation of novel scFv antibody sequences with even higher affinities. Deep screening promises to accelerate biomolecular discovery for a wide range of modalities and targets.

15:35 - 16:05
Principles of Synthetic Genomes Modules
Tom Ellis, Imperial College Centre for Synthetic Biology & Department of Bioengineering, Imperial College, London

The international project to construct a synthetic version of the yeast genome (Sc2.0) has been one of the highest visibility research projects in synthetic biology in the last decade. As this grand project draws to a close, Sc2.0 partners are now beginning to use the tools and knowledge of synthetic yeast genome assembly to ask new questions of yeast biology and genomics, and develop new biotechnologies. As a milestone towards custom, modular genome, we are now using synthetic genome workflows and multiplex CRISPR to examine and exploit Synthetic Genome Modules (SGMs), where sets of genes that encode a common function are relocated from their native genomic loci into new synthetic defragmented or refactored gene clusters in the chromosomes. We have used our SGM method to fine-tune pheromone sensing for biosensor systems, and are now employing it to the explore the minimal gene set for the cell cycle. In new work, we have written SGMs for aromatic amino acid biosynthesis pathways and are using these as a test bed for building new tools for inducible heterochromatin-silencing and other forms of master regulation.

16:05 - 16:35
Toward A World of ElectroGenetics
Martin Fussenegger, Department of Biosystems Science and Engineering, ETH Zurich, Zurich

With the advent of the internet of things, interconnected electronic devices are starting to dominate our daily lives and are reaching the control complexity of living systems, and yet work radically different: While human metabolism uses ion gradients across insulated membranes to simultaneously process slow analog chemical reactions and communicate information in multicellular systems via soluble or volatile molecular signals, electronic devices use multicore central processing units to control the flow of electrons through insulated metal wires with gigahertz frequency and communicate information across networks via wired or wireless connections. While analog biological systems and digital electronic devices efficiently work in their respective worlds there are no efficient interfaces between electronics and genetics. We will report our first attempts to design direct electro-genetic interfaces and our progress toward a world of ElectroGenetics and the internet of the body.

18:00 - 19:00
Ethics Panel

Engineering Life sciences: do we need a paradigm change in bioethical reflection?
Renzo Pegoraro, Pontifical Academy for Life, Rome
Robert Smith, University of Edinburgh, Edinburgh
Martin Fussenegger, ETH Zurich, Zurich
Ralf Stutzki, NCCR MSE

Cutting-edge transdisciplinary research combining biology and engineering allows deep interventions in living organisms and will substantially impact human health and disease treatment. The lack of adequate science-communication strategies and a research pace that outruns traditional bioethical concepts warrant a new setting for moral discourse.

• How realistic is a call for a radical rethinking in our moral reflection?
• How can we translate the highly complex field of molecular systems engineering and the data it produces into a language that can be understood by all?
• Is the scientific community willing to enable the non-scientific society at large to participate in a discourse on par even if this redefines the settings of power along with the right to analyze, interpret and evaluate the “Engineering Life” research?