The 2025 Lectures in Biology and Chemistry: Re-engineering Biology: Directed Evolution of Enzymes and Cellular Pathways

Biological systems have evolved over billions of years, with natural selection favoring the re-shaping of molecular structures and metabolic pathways that enhance survival in a continuously fluctuating chemical environment. Yet these solutions, optimized for fitness rather than human utility, are often suboptimal for applications in areas such as efficient chemistry, renewable energy, and medicine.

Biological systems have evolved over billions of years, optimizing molecules and metabolic pathways for survival within specific environmental contexts. However, these natural solutions are not always ideal for human needs, particularly in areas such as sustainable chemistry, renewable energy, and medicine.

Directed evolution—a methodology inspired by natural selection but conducted in the laboratory—enables scientists to engineer proteins, enzymes, and even entire metabolic pathways with enhanced or novel functionalities. This approach involves iterative rounds of mutation and selection to traverse the vast "fitness landscapes" of molecular function. Initially laborious and time-consuming, directed evolution has become a central strategy in modern biotechnology, thanks to significant advances in high-throughput screening, rational design, and computational modeling.

The pioneering work of Frances Arnold, awarded the Nobel Prize in Chemistry in 2018, demonstrated that laboratory evolution can reliably outperform rational design in engineering complex molecular functions. Her contributions established directed evolution as a transformative force across chemistry and biology.

TBeyond individual enzymes, synthetic biology has emerged as a complementary field, aiming to build and rewire entire cellular processes. Researchers are designing new-to-nature metabolic pathways, including those capable of capturing and converting CO₂, offering novel solutions to climate and sustainability challenges. Advances in membrane biology, minimal cell design, and the recreation of basic metabolic modules have further expanded the scope of cellular engineering. Recent work has also broadened the focus of re-engineering biology beyond catalysis to the fine-tuning of protein conformational landscapes and dynamic regulation. Insights from statistical thermodynamics and free-energy landscape theory are reshaping our understanding of how allosteric networks evolve and adapt, balancing affinity, efficiency, and environmental responsiveness. Strategies now aim not only to optimize catalysis, but also to reprogram internal communication networks and the dynamic behavior of proteins, enabling the design of more adaptable and responsive molecular systems.

Technological innovations have further reshaped the landscape. Ultrahigh-throughput methods, such as droplet-based microfluidics, allow millions of enzyme variants to be screened rapidly, accelerating the exploration of protein sequence space. Concurrently, developments in real-time biosensing and wearable molecular monitors are beginning to bridge the gap between engineered biological systems and direct clinical or industrial applications.

Artificial intelligence has entered the field as a powerful accelerator. Large-scale protein language models and AI-driven structure prediction tools are enabling the in-silico design of functional biomolecules at an unprecedented pace, opening vast new territories for synthetic biology and biotechnology.

This year’s Onassis Lectures are devoted to the advances, challenges, and future prospects of re-engineering biology through directed evolution and synthetic cellular pathways. The series will highlight groundbreaking technologies and conceptual innovations, featuring presentations from world leaders in enzyme engineering, synthetic metabolism, minimal cell construction, thermodynamic modeling of protein evolution, and AI-driven biological design.

Arnold Frances
Professor, California Institute of Technology, USA,
Nobel Prize (2018) in Chemistry

Erb Tobias
Professor, Max Planck Institute for Terrestrial Microbiology, Germany

Gouridis Giorgos
Group Leader, Institute of Molecular Biology & Biotechnology - FORTH, Greece

Hilser Vincent
Professor, John Hopkins University, USA

Hilvert Donald
Professor, ETH Zurich, Switzerland

Moore Jeffrey
Dr, Merck, USA

Plaxco Kevin
Professor, University of California, USA

Poolman Bert
Professor, University of Groningen, The Netherlands

Rives Alexander
Professor Broad Institute of MIT and Harvard, USA

IN PREPARATION

Deadline for Application Saturday May 31, 2025 Participants     Researchers, Postdoctoral Associates, Graduate and advanced Undergraduate students. Financial Aid     The Onassis Foundation will support travel and accommodation expenses for up to thirty five Greek students and up to fifteen International students, selected on the basis of their academic performance. The financial aid for the travel of non-European students cannot exceed the maximum amount of the reimbursement provided for the travel of European students. Interested students should attach to their CV, a list of courses taken, their grades and two letters of recommendation. Excellent knowledge of English is required. Certificate     Students admitted on the basis of their academic performance will receive a certificate after successful participation in the lectures.   Application Form* *Please use latin characters Dear Sir, I wish to participate in "The 2025 Lectures in Biology and Chemistry " First Name: Last name: Affiliation: Address: Telephone: E-mail: Please attach your CV (if applicable): (Select your CV file from your computer). Additional Requirements for Students Graduate students should attach their CV with a detailed description of their studies so far. Advanced undergraduate students should add to their CV a list of courses taken and their grades. Two letters of recommendation should be sent by E-mail directly by the recommending persons to: OnassisF@admin.forth.gr

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