One of the most remarkable examples of self-organized structure formation is the development of a complex organism from a single fertilized egg. With the identification of molecules that participate in this process of morphogenesis, attention has now turned to capturing the physical principles that govern the emergence of biological form. What are the physical laws that govern the dynamics and the formation of structure in living matter? Much of the force generation that drives morphogenesis stems from the actomyosin cortical layer of cells just underneath the cell surface, which endows the surface with the ability to generate active stresses and active torques that can drive reshaping. We combine theory and experiment and investigate how the actomyosin cell surface deforms and how it supports chiral rotations, and how these events together participate in chiral morphogenesis and the establishment of a left-right principal body axis in both the nematode worm and the Japanese quail.

If you would like to attend the seminar, please register here.

Unraveling the origin of life, and how the road to life was punctuated by transitions toward complexity, from astrochemistry to biomolecules and eventually to living organisms, remains one of the greatest challenges that humanity faces. Since Oparin's groundbreaking article a century ago, various scientific disciplines have approached this problem from isolated perspectives. Despite the remarkable progress made, achieving these ambitious goals still entails significant difficulties, and disruptive and more interdisciplinary, holistic approaches have been advocated recently as the way forward.

In this seminar, I will address the main unresolved difficulties associated with the field of the origin and early evolution of life and explore how complexity science, in harmony with recent advances in data science, can play a pivotal role in tackling them. In addition, I will describe several theoretical, modeling and computational approaches under development in our research group [1-4], outlining the opportunities for complexity theory and network science in different scenarios of increasing complexity related to the origin of life. These scenarios range from interstellar astrochemistry, where the most basic building blocks of life are formed, to the emergence of molecular complexity during prebiotic chemistry, and finally to more complex molecular self-organization levels leading to the first replicative cell.

If you would like to attend the seminar, please register here.

[1] C. Alejandre, A. Aguirre-Tamaral, C. Briones and J. Aguirre, Polymerization and replication of primordial RNA induced by clay-water interface dynamics, submitted (2025).

[2] M. Fernández-Ruz, I. Jiménez-Serra and J. Aguirre, A theoretical approach to the complex chemical evolution of phosphorus in the interstellar medium, Astrophysical Journal 956, 47 (2023).

[3] M. García-Sánchez, I. Jiménez-Serra, F. Puente-Sánchez, J. Aguirre, The emergence of interstellar molecular complexity explained by interacting networks, PNAS 119 (30), e2119734119 (2022).

[4] J. Aguirre, Life finds a way, Nature Ecology & Evolution 6 (11), 1599 (2022).

Fluorescence microscopy is a key tool for studying biological systems, yet extracting physical insights from 3D images remains challenging. Meanwhile, tissue models are becoming increasingly sophisticated, but direct integration with imaging data is still limited.

In this talk, I will present our recent efforts to bridge this gap. I will introduce a segmentation and 3D tension inference method that generates detailed mechanical atlases of embryos and tissues from microscopy images. I will then discuss our computational foam-like tissue models, which incorporate viscous dissipation, cell division, and mechanochemical feedback.

Finally, I will showcase a fully differentiable optimization pipeline that links mechanical models to microscopy by generating realistic synthetic images from simulations, paving the way for solving inverse mechanical problems. I will conclude with perspectives on integrating AI with biophysical models to uncover cell behavior in development.

If you would like to attend the seminar, please register here.

During development, initially equivalent cells acquire different identities, in a determined spatial order. Although much is known about the mechanisms through which fates are specified, the dynamics by which spatial patterns arise, and the underlying logic, often remain elusive. Drawing on several concrete examples, I will present a geometric approach to cell fate specification - in the spirit of Waddington's epigenetic landscape - and discuss its implications for how we can approach the collective dynamics of self-organized patterning.

If you would like to attend the seminar, please register here.

Epithelial sealing is a fundamental process occurring during animal development and tissue repair. During this process, mechanical forces are coordinated in order to rearrange biological tissues and ensure a perfect sealing of the epithelium. The mechanisms at the origin of the generation and regulation of these forces during development and wound healing to ensure correct cell positioning and tissue shaping remain elusive. Using Drosophila as a model system, my group is interested in understanding the principles underlying the control of epithelial sealing during embryogenesis and during tissue repair. Here, I will start by presenting how tissue respond to mechanical stretch during tissue sealing in embryonic development. I will highlight the similarities between processes of tissue sealing in development and wound healing. I will then show new results on how the mechanics of sealing is impacted by the size of the gap and present a quantitative model of epithelial mechanics and sealing during wound healing. Finally, I will show how cells can sense mechanical changes occurring during wound generation and how they actively respond to these dramatic tensional changes. I will particularly focus on how wound generation affect chromatin and nuclear architecture and, as a consequence, how changes in chromatin architecture can impact cellular mechanics. 

If you would like to attend the seminar, please register here.

The repressilator, a genetic circuit of three genes repressing each other to create oscillatory behavior, was one of synthetic biology’s earliest breakthroughs, showcasing the ability to engineer complex gene regulatory networks. Twenty-five years later, synthetic oscillators continue to fascinate.

In this talk, I will first present our work on developing a CRISPR-based repressilator—the "CRISPRlator"—in Escherichia coli and its application in Streptococcus pneumoniae to control capsule production, yielding the "CAPSUlator", as well as its use in a light biosensor. I will then introduce the "Optoscillator," an optogenetic version of the repressilator. Analogous to a clock and wavefront mechanism, in a growing bacterial colony harbouring the repressilator, the periodic oscillations are transformed into spatial ring patterns. We analysed the rings when the cells were subjected to different regimes of light exposure. By combining experiments with mathematical modelling, we demonstrated that this simple circuit can exhibit complex dynamics under external periodic forcing, including synchronization, resonance, period doubling, period-4 behaviour, and even chaos. I will conclude with our ongoing efforts to study coupled synthetic oscillators and expand into multicellular consortia.

If you would like to attend the seminar, please register here.

The cell cycle is a tightly regulated process that ensures accurate genetic replication and transmission of cellular states across generations. Pluripotent stem cells (PSCs) exhibit a unique balance of robust self-renewal and responsiveness to differentiation cues, resulting in a rapid cell cycle and a heterogeneous, asynchronous differentiation process in vitro. Evidence suggests that the activation of cell-type-specific genes is confined to the G1 phase, which lengthens during differentiation, hinting at a critical link between cell-cycle regulation, pluripotency, and differentiation. However, the regulators and epigenetic mechanisms governing this relationship remain unclear. To address this question, we have developed a novel approach to study gene expression and chromatin accessibility dynamics during the cell cycle. We combined high-depth single-cell multiome sequencing, biophysical modeling, and advanced deep learning techniques. We first used a novel deep learning tool to assign cell cycle phases to individual cells based on spliced and unspliced mRNA levels. Then, we developed a biophysical model that describes mRNA metabolism, including synthesis, splicing, nuclear export, and degradation. Our approach allowed us to unveil temporal waves of transcriptional and post-transcriptional regulation, controlling mRNA synthesis, degradation, and nuclear export during the cell cycle. Additionally, we quantified chromatin accessibility dynamics and identified transcription factor activities at high temporal resolution, uncovering key TFs that coordinate cell-cycle regulation, including known pluripotency factors. Finally, we applied our approach to spatial transcriptomics to study the spatial organization of the cell cycle in tissues and tumors. Overall, we believe that our novel approach will open the possibility to shed new light on the interplay between cell cycle regulation and cell plasticity in health and disease.

If you would like to attend the seminar, please register here.

Propagating, storing and processing information is key to take smart decisions – for organisms as well as for autonomous devices. In search for the minimal units that allow for complex behaviour, the slime mould Physarum polycephalum stands out by solving complex optimization problems despite its simple make-up. Physarum’s body is an interlaced network of fluid-filled tubes lacking any nervous system, in fact being a single gigantic cell. Yet, Physarum finds the shortest path through a maze. We unravel that Physarum’s complex behaviour emerges from the physics of active flows shuffling through its tubular networks. Flows transport information, information that is stored in the architecture of the network. Thus, tubular adaptation drives processing of information into complex behaviour. Taking inspiration from the mechanisms in Physarum we outline how to embed complex behaviour in active microfluidic devices and how to program human vasculature.

If you would like to attend the seminar, please register here.

Mutations in tumours can serve as markers that allow tracking of past evolution from current samples but also provide insights into future dynamics. In this talk, I present two limiting cases: The first case is a collaboration with the Weghorn lab where we explore the spatio-temporal dynamics of early tumours. We leverage published data from resected hepatocellular carcinomas, each with several hundred samples taken in two and three dimensions. Using spatial metrics of evolution, we find that tumour cells grew predominantly uniformly within the tumour volume rather than at its boundary. We examine how mutations and cells are dispersed throughout the tumour and how cell death contributes to the overall tumour growth. The second case focuses on late tumour evolution under molecularly targeted therapy. In practice, targeted therapy is severely limited by the expansion of therapy-resistant mutants which typically preexist at the start of treatment. How many distinct resistance mechanisms can be found in a realistically-sized population of tumour cells? And can all of them be treated upfront by a suitable combination therapy? An answer is provided for a cell-line model of non-small cell lung cancer.

If you would like to attend the seminar, please register here.

It has been argued that the historical nature of evolution makes it a highly path-dependent process. Under this view, the outcome of evolutionary dynamics could result in organisms with different forms and functions. At the same time, there is ample evidence that convergence and constraints strongly limit the domain of the potential design principles that evolution can achieve. Are these limitations relevant in shaping the fabric of the possible? Here, we argue that fundamental constraints are associated with the logic of living matter. We illustrate this idea by considering the thermodynamic properties of living systems, the linear nature of molecular information, the cellular nature of the building blocks of life, the limits to multicellular complexity, the threshold nature of computations in cognitive systems, and the discrete nature of the architecture of ecosystems. In all these examples, we present available evidence and suggest potential avenues towards a well-defined theoretical formulation. One implication of this proposal is that life elsewhere should share profound commonalities with the life we know from our biosphere, and potential synthetic living designs might also be deeply constrained by the same universal principles.

If you would like to attend the seminar, please register here.