Yuval Elani, Imperial College London, UK

Synthetic cells (SynCells) are bio‑inspired micromachines constructed from molecular building blocks that mimic the form and function of biological cells. Despite their promise, most SynCells remain structurally simplistic, primarily consisting of spherical liposomes, in contrast to their biological counterparts, which are highly compartmentalised. Because form and function are tightly intertwined, this lack of architectural complexity limits the emergence of more sophisticated behaviours.

In this talk, I will describe how we overcome these limitations by employing microfluidic assembly lines for SynCell production, enabling the generation of a wide repertoire of SynCell architectures. This, in turn, allows the creation of synthetic cells with emergent behaviours, including motility, bioproduction, cell–cell communication, collective actuation, and responsiveness to a variety of stimuli such as temperature, light, and magnetic fields.

In addition, we have recently expanded our toolkit to access the nanoscale by using automated approaches to generate and screen liposome libraries. Combined with rational design, this enables the construction of nano‑organelles for multi‑stage release of different payloads at defined time points, as well as the development of attolitre bioreactors for in situ biochemical synthesis.

Ania Fryszkowska, Novartis, CH

The construction of molecular complexity is a central challenge in modern drug discovery and development, driven by increasingly sophisticated therapeutic modalities, rising sustainability expectations, and compressed development timelines. Enabled by advances in directed evolution, computation, automation, and analytics, biocatalysis has evolved from a niche synthetic tool into a broadly enabling and programmable technology, reshaping how molecules are designed, synthesized, and manufactured across the pharmaceutical pipeline.

This talk offers an industry perspective on the evolving landscape of biocatalysis in pharma, highlighting how integrated industrial teams are driving the adoption of enzymes as versatile, scalable, and designable catalysts across the pipeline. Through selected case studies spanning small molecules, peptides, and bioconjugates, it illustrates how engineered enzymes enable efficient C–C and C–N bond formation, access to stereochemically dense motifs, and site‑selective functionalization—transformations that remain challenging for traditional chemical synthesis.

Sebastian Hiller, University of Basel, CH

Structural biology is arguably at the height of its time. The integrated use of experimental and AI methods resolves problems at atomic level that have long been out of reach. Thereby, solution NMR spectroscopy is ideal to connect static structures towards their functional dynamics.

I will describe recent successes to employ solution NMR spectroscopy in such integrated setups, emphasizing the interplay between the different methods. Our journey starts with protein biogenesis in the endoplasmic reticulum (ER), where newly synthesized nascent chains are refolded by a network of molecular chaperones. We discover biomolecular condensates as the organizing principle of this chaperone network and report detailed functional and structural studies.

We then resolve the complete functional cycle of an ATP-driven molecular machine, the Hsp70 chaperone BiP, at atomic level. We create a non-equilibrium steady-state under turnover conditions inside the NMR to resolve that BiP undergoes a branched functional cycle that is regulated by two autoinhibition switches.

Finally, we leverage protein design to establish an experimental pipeline for high-throughput characterization of protein structure and dynamics by NMR. With this setup, a single operator can produce and analyze hundreds of proteins per week at minimal cost, unlocking a new regime of statistical structural biology, where sequence–structure–dynamics relationships are gained from experimental ensemble studies of suitably designed proteins.

Kathrin Lang, ETH Zurich, CH

Nature uses a limited set of twenty amino acids to synthesize proteins. In recent years, it has become possible to site-specifically incorporate designer amino acids with new chemical properties into proteins in living cells by reprogramming the genetic code. Continued advances have substantially improved the efficiency, fidelity, and scope of genetic code expansion technologies, enabling their broader application across complex biological systems. In parallel, the development of selective chemical reactions that operate within living systems has further strengthened the impact of these approaches on studying biological processes.

In this talk, I will present our lab’s efforts to expand the genetic code and to endow proteins with novel chemical functionalities within their physiological environment. By engineering more efficient and versatile genetic code expansion systems, we have enhanced the incorporation of noncanonical amino acids and enabled their application in increasingly challenging cellular contexts. Using these advances, we have developed tools to image and probe proteins, to study protein-protein interactions and stabilize low-affinity protein complexes, to investigate posttranslational modifications and to re-engineer and manipulate molecular networks and biological pathways such as ubiquitylation and SUMOylation in living cells.

We envision that ongoing improvements in efficiency and scope of genetic code expansion, together with the ability to encode complex posttranslational modifications, will enable the study of biological processes that are difficult or impossible to address by more classical methods.

David A. Leigh, University of Manchester, UK

Over the last three decades examples of synthetic molecular machines and motors have been developed, albeit primitive by biological standards. Such molecules are best designed to work through statistical mechanisms. In a manner reminiscent of Maxwell’s Demon, random thermal motion is rectified through ratchet mechanisms, giving chemistry direction.

It is increasingly being recognised that similar concepts can be applied to other chemical exchange processes. Ratchet mechanisms—effectively chemical engines in which catalysis of ‘fuel’ to ‘waste’ is used to drive another chemical process—can cause directional impetus in what are otherwise stochastic systems, including endergonic chemical reactions. This is ushering in a new era of non-equilibrium chemistry, providing fundamental advances in functional molecule design and the first examples of molecular robotics, overturning existing dogma and offering fresh insights into biology and molecular nanotechnology.

Stephen Mann, University of Bristol, UK

Recent progress in the chemical construction of compartmentalized semipermeable microscale objects comprising embodied cytomimetic functions is paving the way towards rudimentary forms of artificial cell-like materials (protocells/prototissues) as a step towards future proto-living technologies.

In this talk, I will demonstrate simple forms of individuated and collective molecular systems engineering in synthetic protocell networks. I will discuss recent studies on implementing programmable agency in synthetic protobiology, including: (i) enzyme-powered sensing, motility and oscillation; (ii) superstructural ordering and communication; (iii) information processing; (iv) spatiotemporal feedback; and predator-prey interactivity.

These studies offer new pathways towards intelligent matter based on artificial life materials capable of autonomic behaviour and programmable agency.

José Luis Mascareñas, University of Santiago de Compostela, ES

Transition metal complexes have proven invaluable across a broad spectrum of scientific disciplines, including catalysis, synthesis, photophysics, and supramolecular chemistry. Their diverse coordination geometries and redox properties, combined with the ability to fine-tune these characteristics through ligand modification, offer extensive opportunities for developing novel reactivities and tailored physicochemical responses.

Our research has focused on leveraging the unique features of transition metal complexes in catalysis, synthesis, and chemical biology. In recent years, we have explored the feasibility of adapting organometallic catalysis to function in biological environments, including within living mammalian cells. This endeavour poses significant challenges, particularly due to the sensitivity of many metal-catalyzed reactions to air and water, as well as the stringent demands for orthogonality and biocompatibility. Nonetheless, we have successfully developed several intracellular reactions promoted by palladium, ruthenium, and gold complexes.

Krzysztof Palczewski, University of California, Irvine, USA

TBA

Stephen Quake, Stanford University, USA

In this talk I will explore to what extent the genome is a blueprint for an organism and what are some of the key open problems in interpreting the information content of the genome. Among these open problems are the fact that today it is impossible to predict the various cell types of an organism from the genome alone. This has motivated efforts to characterize the molecular composition of various cell types within humans and multiple model organisms, both by transcriptional and proteomic approaches. We used single cell transcriptomics to create a human reference atlas comprising more than one million cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression, and provides an experimental basis to understand the cell type diversity which can be generated from a single genome. We have trained large language models on this data to help understand the relationships between cell types and across evolutionary history.

Pierre Stallforth, Hans Knöll Institute, DE

Microbial natural products remain a critical source of therapeutic agents. These compounds are often shaped by intricate ecological interactions. Predator–prey dynamics between amoebae and bacteria represent particularly rich reservoirs of these secondary metabolites. Amoebae, as ubiquitous bacterivores, exert strong selective pressure, driving bacterial defenses against grazing and, in turn, amoebal counter-adaptations. Within this evolutionary arms race, we investigate the biosynthesis and diversification of amoebicidal natural products, including polymicrobial modifications that expand their chemical repertoire. Extending this perspective into the past, we exploit ancient bacterial DNA to identify and reconstruct biosynthetic genes, providing access to previously untapped natural product diversity.

Savas Tay, University of Chicago, USA

Cells process a diverse set of signals whose type, amplitude and dynamics constantly change, and aberrant signaling leads to inflammation, infection and cancer. We have been using automated live-cell analysis, single cell methods, and computational modeling for nearly two decades to study spatial and temporal characteristics of cellular communication in the immune system. I will describe our recent results on how immune cells process combinatorial and rapidly changing pathogen and cytokine signals by modulating transcriptional dynamics. We show how single cell interactions leads to emergent spatial “patterning” of pro-inflammatory gene expression across populations and tissues. I will introduce a new single cell proteomics technology called proximity sequencing (Prox-seq), which enables simultaneous measurement of proteins, protein complexes and mRNA in thousands of individual cells. Prox-seq combines proximity ligation with single-cell sequencing to measure proteins and their dimers from all pairwise combinations, providing quadratically-scaled multiplexing. Our measurements revealed formation and dissociation of protein complexes during exposure to pathogen inputs, and reveals previously unknown protein interactions in individual cells. I will also describe the extension of proximity sequencing to intact tissues like the germinal center (spatial Prox-seq), revealing functional distributions of proteins, protein complexes, cell-cell interactions and transcripts in the same spatially resolved locations, across thousands of spots in tissue. Finally, I will describe our latest results in high throughput microfluidic systems for automated analysis of tumor cells, organoids and microbial colonies, and their use for combinatorial drug screening in personalized therapy.