Seminars

Cells make decisions across developmental biology, immunology, and synthetic biology. These processes are typically described using systems of ordinary differential equations, where mathematical analysis focuses on steady-state solutions. However, understanding how the timing of cell decisions is controlled requires moving beyond this paradigm. In this talk, I will discuss two complementary molecular mechanisms for controlling dynamical speed. First, I will show how timing can be regulated through critical slowing down, and how combining different bifurcations can generate emergent temporal behaviours even in small gene regulatory networks. Secondly, I will address developmental tempo, where embryos from different species execute remarkably similar genetic programmes at different speeds. I will present a mathematical framework based on orbit invariance that allows us to explore potential molecular mechanisms underlying species-specific differences in developmental timing.

Heterogeneity is a fundamental feature of biological systems. Oncology is one of the fields in which this feature is most evident, as its key players are characterised by mutability, plasticity, and often “uncontrolled” dynamics. Whether heterogeneity arises from spatial structure, environmental variability, or cellular traits, effective therapeutic strategies must explicitly account for it in order to eradicate or control tumours.

From a modern perspective, this requires balancing the hit-hard / keep-it-sensitive trade-off, while also considering not only medical but also broader patient-related side effects of treatments. Contemporary medicine is increasingly exploring ways to exploit the very characteristics that have historically made cancer so dangerous, turning them into potential advantages for therapy.

The multiscale nature of tumour systems, together with the need to predict the combined effects of multiple, non-parallelisable processes, makes the development of optimised mathematical tools particularly compelling. Such tools can address questions that are both scientifically challenging and highly relevant from a clinical and humanitarian perspective.

In this seminar, we will analyse tumour masses from a structured population perspective, focusing on the role of heterogeneity in shaping therapeutic strategies. We will first discuss how heterogeneity in phenotypic composition and nutrient distribution influences the eco-evolutionary dynamics of tumour growth. We will then consider more specifically its impact on radiotherapy.

In particular, we will highlight the advantages of mathematically rigorous modelling in bridging theory and biology. We will also adopt a more exploratory perspective, using these models to illustrate how mathematics can serve as a potential decision-support tool for the selection and optimisation of treatment protocols, within an image- and model-driven framework.

The final part of the seminar will focus on potential future developments, with the aim of fostering an open and collaborative discussion on novel perspectives to improve understanding, prediction, and therapeutic optimisation.

Many cells exhibit exponential growth not only at the population level but also at the single-cell level. However, single-cell growth rates fluctuate over time. We distinguish between two conceptually distinct sources of growth rate fluctuations: intrinsic continuous fluctuations resulting from intracellular processes, and fluctuations that originate at division events, which we refer to as kicks. We use a simple model to describe single-cell growth and identify the signatures of continuous noise and division kicks. To infer the true biological behavior reliably from experiments, it is crucial to account for measurement noise. We derive analytical expressions for the statistics of meaningful observables, accounting for continuous fluctuations, division kicks, and measurement noise. Importantly, we find that ignoring measurement noise can lead to incorrect biological conclusions. Our results provide insights into how different sources of growth rate variability and measurement errors influence observed cell size dynamics, offering an interpretable framework for analyzing experimental data in cellular biology. 

Mechanistic ordinary differential equation (ODE) models are a powerful tool to study dynamic biological systems. However, their predictive power is constrained by gaps, biases, and inconsistencies in the literature. They typically also require quantitative time-lapse data for training, which is time-consuming to collect. At the same time, machine-learning approaches can capture complex patterns from data, but they are often harder to interpret and typically require large training datasets. Hybrid scientific machine learning (SciML) models offer a promising way to combine the strengths of both approaches by integrating mechanistic models with flexible data-driven modules. 
Despite this promise, the use of SciML in biology remains limited by insufficient infrastructure. Dedicated software is needed because coding end-to-end differentiable workflows for gradient-based training of hybrid models is technically challenging. In addition, model exchange is hindered by the lack of a standardized, reproducible format for specifying SciML training problems, analogous to the PEtab standard for ODE models. To address these challenges, we developed PEtab-SciML, an extension of the PEtab format, and implemented support for it in the state-of-the-art modeling toolboxes PEtab.jl and AMICI. In this seminar, I will introduce the PEtab-SciML format. Using real-data examples, I will show how PEtab-SciML enables the integration of diverse data modalities into dynamic model training; such as learning the kinetic parameters of an ODE model from omics and protein sequence data. I will also show how it supports machine-learning-based black-boxing of complex model components, such as quarantine strength in an SIR model. Finally, I will show how PEtab-SciML enables the use of efficient training strategies, such as curriculum learning, that make SciML models easier to train and apply in practice. 

Stochastic search is ubiquitous in biology and ecology, from synaptic transmission and intracellular signaling to predators seeking prey and the spread of disease. In dynamic systems like these, the number of 'searchers' is rarely constant: new agents may be recruited while others can abandon the search. Despite the ubiquity of these dynamics, their combined influence on search times remains largely unexplored. In this talk we will introduce a general framework for stochastic search in which agents progressively join and leave the process, a mechanism we term 'dynamic redundancy and mortality'. Under minimal assumptions on the underlying search dynamics, our framework yields the exact distribution of the first-passage time to a target region and further reveals surprising connections to stochastic search with stochastic resetting, wherein a single searcher is randomly 'reset' to its initial state. We will then treat the target region as a queue, which we show has interarrival times governed by a thinned nonhomogeneous Poisson process. Altogether this work provides a rigorous foundation for studying stochastic search processes with a fluctuating number of searchers. This work is in collaboration with Dr. Aanjaneya Kumar (Santa Fe Institute) and José Giral-Barajas (Imperial College London).