In this talk I will discuss how phenotypic heterogeneity affects emergent pattern formation in living active matter with chemical communication between cells. In doing so, I will explore how the emergent dynamics of multicellular communities are qualitatively different in comparison to the dynamics of isolated or non-interacting cells. I will focus on two specific projects. First, I will show how genetic regulation of chemical communication affects motility-induced phase separation in cell populations. Second, I will demonstrate how chemotaxis along self-generated signal gradients affects cell populations undergoing 3D morphogenesis.
The role of tissue stiffness in controlling cell behaviours ranging from proliferation to signalling and activation is by now well accepted. A key focus of experimental studies into mechanotransduction are focal adhesions, localised patches of strong adhesion, where cell signalling has been established to occur. However, these adhesion sites themselves alter the mechanical equilibrium of the system determining the force balance and work done. To explore this I have developed an active matter continuum description of cellular contractility and will discuss recent results on the specific role of spatial positioning of adhesions in mechanotransduction. I show using energy arguments why the experimentally observed arrangements of focal adhesions develop and the implications this has for stiffness sensing and cellular contractility control. I will also show how adhesions play distinct roles in single cells and tissue layers respectively drawing on recent experimental work with Dr JR Davis (Manchester University) and Dr Nic Tapon (Crick Institute) with applications to epithelial layers and organoids.
Optimal transport (OT) proves to be a powerful tool for non-parametric calibration: it allows us to take a favourite (non-calibrated) model and project it onto the space of all calibrated (martingale) models. The dual side of the problem leads to an HJB equation and a numerical algorithm to solve the projection. However, in general, this process is costly and leads to spiky vol surfaces. We are interested in special cases where the projection can be obtained semi-analytically. This leads us to the martingale equivalent of the seminal fluid-dynamics interpretation of the optimal transport (OT) problem developed by Benamou and Brenier. Specifically, given marginals, we look for the martingale which is the closest to a given archetypical model. If our archetype is the arithmetic Brownian motion, this gives the stretched Brownian motion (or the Bass martingale), studied previously by Backhoff-Veraguas, Beiglbock, Huesmann and Kallblad (and many others). Here we consider the financially more pertinent case of Black-Scholes (geometric BM) reference and show it can also be solved explicitly. In both cases, fast numerical algorithms are available.
Based on joint works with Julio Backhoff, Benjamin Joseph and Gregoire Leoper.
This talk reports a work in progress. It will be done on a board.
Please join us for refreshments outside L3 from 1530.
Predicting real-world phenomena often requires an understanding of their causal relations, not just their statistical associations. I will begin this talk with a brief introduction to the field of causal inference in the classical case of structural causal models over directed acyclic graphs, and causal discovery for static variables. Introducing the temporal dimension results in several interesting complications which are not well handled by the classical framework. The main component of a constraint-based causal discovery procedure is a statistical hypothesis test of conditional independence (CI). We develop such a test for stochastic processes, by leveraging recent advances in signature kernels. Then, we develop constraint-based causal discovery algorithms for acyclic stochastic dynamical systems (allowing for loops) that leverage temporal information to recover the entire directed graph. Assuming faithfulness and a CI oracle, our algorithm is sound and complete. We demonstrate strictly superior performance of our proposed CI test compared to existing approaches on path-space when tested on synthetic data generated from SDEs, and discuss preliminary applications to finance. This talk is based on joint work with Georg Manten, Cecilia Casolo, Søren Wengel Mogensen, Cristopher Salvi and Niki Kilbertus: https://arxiv.org/abs/2402.18477 .
Please join us for refreshments outside L3 from 1530.
For many systems (certainly those in biology, medicine and pharmacology) the mathematical models that are generated invariably include state variables that cannot be directly measured and associated model parameters, many of which may be unknown, and which also cannot be measured. For such systems there is also often limited access for inputs or perturbations. These limitations can cause immense problems when investigating the existence of hidden pathways or attempting to estimate unknown parameters and this can severely hinder model validation. It is therefore highly desirable to have a formal approach to determine what additional inputs and/or measurements are necessary in order to reduce or remove these limitations and permit the derivation of models that can be used for practical purposes with greater confidence.
Structural identifiability arises in the inverse problem of inferring from the known, or assumed, properties of a biomedical or biological system a suitable model structure and estimates for the corresponding rate constants and other model parameters. Structural identifiability analysis considers the uniqueness of the unknown model parameters from the input-output structure corresponding to proposed experiments to collect data for parameter estimation (under an assumption of the availability of continuous, noise-free observations). This is an important, but often overlooked, theoretical prerequisite to experiment design, system identification and parameter estimation, since estimates for unidentifiable parameters are effectively meaningless. If parameter estimates are to be used to inform about intervention or inhibition strategies, or other critical decisions, then it is essential that the parameters be uniquely identifiable.
Numerous techniques for performing a structural identifiability analysis on linear parametric models exist and this is a well-understood topic. In comparison, there are relatively few techniques available for nonlinear systems (the Taylor series approach, similarity transformation-based approaches, differential algebra techniques and the more recent observable normal form approach and symmetries approaches) and significant (symbolic) computational problems can arise, even for relatively simple models in applying these techniques.
In this talk an introduction to structural identifiability analysis will be provided demonstrating the application of the techniques available to both linear and nonlinear parameterised systems and to models of (nonlinear mixed effects) population nature.
Dispersive nonlinear partial differential equations can be used to describe a range of physical systems, from water waves to spin states in ferromagnetism. The numerical approximation of solutions with limited differentiability (low-regularity) is crucial for simulating fascinating phenomena arising in these systems including emerging structures in random wave fields and dynamics of domain wall states, but it poses a significant challenge to classical algorithms. Recent years have seen the development of tailored low-regularity integrators to address this challenge. Inherited from their description of physicals systems many such dispersive nonlinear equations possess a rich geometric structure, such as a Hamiltonian formulation and conservation laws. To ensure that numerical schemes lead to meaningful results, it is vital to preserve this structure in numerical approximations. This, however, results in an interesting dichotomy: the rich theory of existent structure-preserving algorithms is typically limited to classical integrators that cannot reliably treat low-regularity phenomena, while most prior designs of low-regularity integrators break geometric structure in the equation. In this talk, we will outline recent advances incorporating structure-preserving properties into low-regularity integrators. Starting from simple discussions on the nonlinear Schrödinger and the Korteweg–de Vries equation we will discuss the construction of such schemes for a general class of dispersive equations before demonstrating an application to the simulation of low-regularity vortex filaments. This is joint work with Yvonne Alama Bronsard, Valeria Banica, Yvain Bruned and Katharina Schratz.