L4

We provide a derivation of the fourth-order DLSS equation based on an interpretation as a chemical reaction network. We consider on the discretized circle the rate equation for the process where pairs of particles sitting on the same side jump simultaneously to the two neighboring sites, and the reverse jump where a pair of particles sitting on a common site jump simultaneously to the side in the middle. Depending on the rates, in the vanishing mesh size limit we obtain either the classical DLSS equation or a variant with nonlinear mobility of power type. We identify the limiting gradient structure to be driven by entropy with respect to a generalization of the diffusive transport type with nonlinear mobility via EDP convergence. Furthermore, the DLSS equation with nonlinear mobility of the power type shares qualitative similarities with the fast diffusion and porous medium equations, since we find traveling wave solutions with algebraic tails and polynomial compact support, respectively.    
       

Joint work with Alexander Mielke and Artur Stephan arXiv:2510.07149. The DLSS part is based on joints works with Daniel Matthes, Eva-Maria Rott and Giuseppe Savaré.

More than seventy years after its publication, Turing’s article “The Chemical Basis of Morphogenesis” is still able to surprise its reader, in particular for the power and the depth of its vision. If we know from his biographer, Andrew Hodges, that Turing became interested in embryology and morphogenesis because he wanted to build or, better, to grow a brain, many questions still arise for the reader of the original article: why did Turing – a mathematician, a logician, a cryptographer, one of the fathers of computer science – not use any informational metaphor associated with the notion of “genetic program” in his work on morphogenesis, preferring instead to develop a modelling approach based on a system of partial differential equations ? Where did he draw his modelling inspiration from, both from the point of view of the mathematics and from the point of view of references to biology ? In my presentation I will address these questions by highlighting the morphological connotations of Turing’s work in biology, that can be related to Turing’s interest, in D’Arcy Wentworth Thompson’s classic On Growth and Form (1917). The 1952 article is rather sparse in indications in this regard, which are, however, provided by Turing’s other writings, unpublished during his lifetime, in which he situates his work in continuity with Thompson’s morphological questions. I will also suggest that, as in a virtuous circle, Turing masterfully brings to life a synergy between a morphological look at the living (that implies that his work has a connotation in theoretical biology) and a mathematical exploration of the non-linear, helped by an appropriate and meaningful use of numerical calculus. 

Gravitational instantons are complete 4-dimensional hyperkähler manifolds with square-integrable curvature tensor. I will address the question whether all gravitational instantons (of type ALG) can be obtained as Hitchin moduli spaces. In particular, I will explain how to compute the (hyperkähler) Torelli map for (weakly) parabolic Higgs bundles on the 4-punctured sphere. This is based on recent joint work with Fredrickson, Mazzeo and Swoboda.

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).

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. 

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. 

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.

Prostate cancer progression and therapeutic resistance present significant clinical challenges, particularly in the transition to castration-resistant disease. Although androgen deprivation therapy and second-generation drugs have improved patient outcomes, resistance frequently develops, reflecting tumour heterogeneity and the influence of its microenvironment. This talk presents two interdisciplinary studies that address these issues through data-driven mathematical approaches. We show how integrating experimental data with mathematical and statistical modelling can improve our understanding of prostate cancer dynamics and inform more effective, context-specific therapeutic strategies. The first study examines drug resistance and tumour evolution under treatment. We develop a multi-scale hybrid modelling framework to capture processes occurring across different temporal scales. Partial differential equations describe the behaviour of drugs and other chemicals in the tumour microenvironment (over the ‘fast’ timescale), while a cellular automaton captures the dynamics of tumour cells (over the ‘slow’ timescale). Through computational analysis of the model solutions, we examine the spatial dynamics of tumour cells, assess the efficacy of different drug therapies in inhibiting prostate cancer growth, and identify effective drug combinations and treatment schedules to limit tumour progression and prevent metastasis. The second study focuses on the role of host–microbiome interactions in obesity-associated prostate cancer. Using data from experiments with the TRAMP mouse model, we apply statistical and machine learning methods, including generalised linear models, Granger causality, and support vector regression, to characterise microbial dynamics and their responses to treatment. These findings are incorporated into a dynamical systems framework that captures microbiome–tumour co-evolution under therapeutic and dietary perturbations, providing insight into how dietary fat and combination therapies involving enzalutamide and phytocannabinoids influence tumour progression and gut microbiota composition.