L3

Morphogen protein gradients play an essential role in the spatial regulation of patterning during embryonic development.  The most commonly accepted mechanism of protein gradient formation involves the diffusion and degradation of morphogens from a localized source. Recently, an alternative mechanism has been proposed, which is based on cell-to-cell transport via thin, actin-rich cellular extensions known as cytonemes. It has been hypothesized that cytonemes find their targets via a random search process based on alternating periods of retraction and growth, perhaps mediated by some chemoattractant. This is an actin-based analog of the search-and-capture model of microtubules of the mitotic spindle searching for cytochrome binding sites (kinetochores) prior to separation of cytochrome pairs. In this talk, we introduce a search-and-capture model of cytoneme-based morphogenesis, in which nucleating cytonemes from a source cell dynamically grow and shrink until making contact with a target cell and delivering a burst of morphogen. We model the latter as a one-dimensional search process with stochastic resetting, finite returns times and refractory periods. We use a renewal method to calculate the splitting probabilities and conditional mean first passage times (MFPTs) for the cytoneme to be captured by a given target cell. We show how multiple rounds of search-and-capture, morphogen delivery, cytoneme retraction and nucleation events lead to the formation of a morphogen gradient. We proceed by formulating the morphogen bursting model as a queuing process, analogous to the study of translational bursting in gene networks. We end by briefly discussing current work on a model of cytoneme-mediated within-host viral spread.

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.

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 .

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