Seminars

Immunological health relies on a balance between the ability to mount an immune response against potential pathogens and tolerance to self. However, how we keep that balance in health and what goes wrong in disease is not well understood. Here, I will describe combination of novel experimental and computational approaches using multi-omics datasets, imaging and functional experiments to dissect the role and defects in immune cells across several disease areas in cancer and autoimmunity. We show how shared mechanisms that are disrupted across diseases, including cellular, migration, immuno-surveillance, regulation and activation, as well as the immunological features associated with better prognosis and immunomodulation.

Turing patterns have long been proposed as a mechanism for spatial organization in biology, but their relevance remains controversial due to the stringent fine-tuning often required. In this talk, I will present recent efforts to engineer synthetic Turing systems in bacterial colonies, highlighting both successes and limitations. While our three-node gene circuit generates patterns, challenges remain in extending these results to broader contexts. Additionally, I will discuss our exploration of machine learning methods to address the inverse problem of pattern formation, helping the design process down the road. This work addresses the ongoing task in translating theory into robust biological applications, offering insights into both current capabilities and future directions.

Cells must reliably coordinate responses to noisy external stimuli for proper functionality whether deciding where to move or initiate a response to threats. In this talk I will present a perspective on such cellular decision making problems with extreme statistics. The central premise is that when a single stochastic process exhibits large variability (unreliable), the extrema of multiple processes has a remarkably tight distribution (reliable). In this talk I will present some background on extreme statistics followed by two applications. The first regards antigen discrimination - the recognition by the T cell receptor of foreign antigen. The second concerns directional sensing - the process in which cells acquire a direction to move towards a target. In both cases, we find that extreme statistics explains how cells can make accurate and rapid decisions, and importantly, before any steady state is reached.

We consider a system of interacting particles as a model for a foraging ant colony, where each ant is represented as an active Brownian particle. The interactions among ants are mediated through chemotaxis, aligning their orientations with the upward gradient of a pheromone field. Unlike conventional models, our study introduces a parameter that enables the reproduction of two distinctive behaviours: the conventional Keller-Segel aggregation and the formation of travelling clusters without relying on external constraints such as food sources or nests. We consider the associated mean-field limit of this system and establish the analytical and numerical foundations for understanding these particle behaviours.

Understanding the mechanisms behind the spatial distribution, self-organisation and aggregation of organisms is a central issue in both ecology and cell biology. Since self-organisation at the population level is the cumulative effect of behaviours at the individual level, it requires a mathematical approach to be elucidated.
In nature, every individual, be it a cell or an animal, inspects its territory before moving. The process of acquiring information from the environment is typically non-local, i.e. individuals have the ability to inspect a portion of their territory. In recent years, a growing body of empirical research has shown that non-locality is a key aspect of movement processes, while mathematical models incorporating non-local interactions have received increasing attention for their ability to accurately describe how interactions between individuals and their environment can affect their movement, reproduction rate and well-being. In this talk, I will present a study of a class of advection-diffusion equations that model population movements generated by non-local species interactions. Using a combination of analytical and numerical tools, I will show that these models support a wide variety of spatio-temporal patterns that are able to reproduce segregation, aggregation and time-periodic behaviours commonly observed in real systems. I will also show the existence of parameter regions where multiple stable solutions coexist and hysteresis phenomena.
Overall, I will describe various methods for analysing bifurcations and pattern formation properties of these models, which represent an essential mathematical tool for addressing fundamental questions about the many aggregation phenomena observed in nature.
 

Underlying many biological models are chemical reaction networks (CRNs), and identifying allowed and forbidden dynamics in reaction networks may 
give insight into biological mechanisms. Algebraic approaches have been important in several recent developments. For example, computational 
algebra has helped us characterise all small mass action CRNs admitting certain bifurcations; allowed us to find interesting and surprising 
examples and counterexamples; and suggested a number of conjectures.   Progress generally involves an interaction between analysis and 
computation: on the one hand, theorems which recast apparently difficult questions about dynamics as (relatively tractable) algebraic problems; 
and on the other, computations which provide insight into deeper theoretical questions. I'll present some results, examples, and open 
questions, focussing on two domains of CRN theory: the study of local bifurcations, and the study of multistationarity.

Advances in spatial profiling technologies are providing insights into how molecular programs are influenced by local signalling and environmental cues. However, cell fate specification and tissue patterning involve the interplay of biochemical and mechanical feedback. Here, we propose a new computational framework that enables the joint statistical analysis of transcriptional and mechanical signals in the context of spatial transcriptomics. To illustrate the application and utility of the approach, we use spatial transcriptomics data from the developing mouse embryo to infer the forces acting on individual cells, and use these results to identify mechanical, morphometric, and gene expression signatures that are predictive of tissue compartment boundaries. In addition, we use geoadditive structural equation modelling to identify gene modules that predict the mechanical behaviour of cells in an unbiased manner. This computational framework is easily generalized to other spatial profiling contexts, providing a generic scheme for exploring the interplay of biomolecular and mechanical cues in tissues.