time speaker title and abstract
15:00 Welcome
15:00-15:45 Nick Jones
In this talk I consider why many, empirically observed, directed networks might contain a lack of feedback loops. An answer might be network growth mechanisms that favour clear trophic levels and which generate assymetries between the in degrees and out degrees of nodes. This is a partial answer to May’s (Complexity-Stability) Paradox. Finally I will outline an, ageing relevant, concrete biological example of spatial demographic stochasticity where altruists can dominate a system even when actively selected against.
15:45-16:00 Jacob Cook

Entropy production is a hallmark of nonequilibrium processes in stochastic thermodynamics. Multistable nonequilibrium systems are abundant outcomes of nonlinear dynamics with feedback yet relatively little is known about what determines the stability of the steady states and their switching rates in terms of entropy and entropy production. Here, we will link the fluctuation theorem for the entropy production along trajectories and the large-deviation approach of minimum- action-path theory to elucidate the thermodynamics of steady-state switching. Interestingly, we find that the entropy production at steady state plays no explicit role, but the entropy production along switch- ing trajectories is key. Alternative stabilising and destabilising mech- anisms such as steady-state entropy and diffusive noise are also investigated.
16:00-16:15 Charlie Duclut

We consider a large number of chemotactic cells that diffuse, die, divide and interact at long range via the release of chemicals. We investigate the dynamics at long time and focus on the phase transition that occurs between a dilute and a dense phase using a renormalization group analysis. If we consider only interactions that conserve the particles number, exact scaling exponents can even be obtained; this analysis predicts in particular a superdiffusive behaviour of the cells close to the phase transition.

16:15-16:45 Patrick Wilke

Motivated by recent experimental studies that have addressed the stepping behavior of kinesins, we investigate a lattice gas model for simulta- neous transport of two species of active particles on a microtubule. The species are distinguished by their different gaits: While the first species moves straight ahead, the second follows a helical path. We show that the collective properties of such systems critically differ from those of one-species transport as described by generalised totally asymmetric exclusion processes. This is most evident in a jamming transition far below full occupation, as well as in nonequilibrium pattern formation. The altered behavior arises because - unlike the case in single-species transport - any given position may be targeted by two particles from different directions at the same time. However, a particle can leave a given position only in one direction. This simple change in connec- tivity significantly amplifies the impact of steric interactions and thus becomes a key determinant of mixed species transport. We computationally characterize this type of hindrance and develop a comprehensive stochastic theory for collective two-species transport along a cylinder. Our observations show high robustness against model extensions that account for additional biomolecular features which suggests relevance also in a biological context.
16:45-17:00 15 min break
17:00-17:45 Susan Cox

Super-resolution microscopy is a powerful tool for imaging structures at a lengthscale of tens of nm, but its utility for live cell imaging is limited by the time it takes to acquire the data needed for an image. For localisation microscopy the acquisition time can be cut by more than two orders of magnitude by using advanced algorithms which can analyse dense data, trading off acquisition and processing time. Information can be traded for resolution: for example, the whole dataset can by modelled as arising from blinking and bleaching fluorophores (Bayesian analysis of Blinking and Bleaching), although at a high computational cost. However, all these approaches will come with a risk of artefacts, which can mean that the image does not resemble the underlying sample. We have recently developed Harr Wavelet Kernel Analysis, a multi-timescale prefiltering technique which enables high density imaging without artefacts. The results of benchmarking with other techniques reveal that at high activation densities many analysis approaches may achieve high apparent precision (very sharp images), but poor accuracy (the images don’t look like the sample). I will discuss the relationship between precision, accuracy and information content in super-resolution microscopy images.

17:45-18:00 Benjamin Walter

I present some joint work with Gunnar Pruessner (Imperial College London, UK) and Guillaume Salbreux (Francis Crick Institute, UK) on first passage times in non-markovian stochastic dynamics. A Brownian particle in a potential is coupled weakly to an external noise with finite autocorrelation time. Starting from a Darling-Siegert type renewal equation, we develop a perturbative approach to find a controlled expansion for the full moment generating function of the first passage time distribution in powers of the coupling strength. This perturbative scheme can be understood diagrammatically. I illustrate the framework with two analytically solvable models, namely by adding coloured noise to Brownian motion on a ring and to the Ornstein-Uhlenbeck process.

18:00-18:30 Francesc Font-Clos

We construct a topographic map underlying epithelial-mesenchymal plasticity by combining numerical simulations, statistical physics methods and analysis of bulk and single-cell gene expression data. The map reveals a multitude of metastable hybrid phenotypic states, separating stable epithelial and mesenchymal states, and is reminiscent of the free energy measured in glassy materials and disordered solids.

18:30-18:45 Núria Folguera-Blasco

The inherent capacity of differentiated cells to switch their pheno- type in vivo in response to damage stimuli might have a pivotal role in ageing and cancer. However, how the mechanisms of phenotype reprogramming are established remains poorly understood. In order to elucidate such mechanisms, we present a stochastic model of com- bined epigenetic regulation (ER)-gene regulatory network (GRN) to study the plastic phenotypic behaviours driven by ER heterogeneity.

Our analysis of the coupled system reveals the existence of pluripotent stem-like and differentiated steady-states. Crucially, ER heterogeneity is responsible for conferring abnormal robustness to pluripotent stem-like states, which cause the locking of the cells in a stem cell-like state prone to cancer development. By analysing the ER heterogeneity, we formulate epigenetic heterogeneity-based strategies capable of unlocking and facilitating the transit from differentiation-refractory (pluripotent stem-like) to differentiation-primed epistates. Our results suggest that epigenetic heterogeneity regulates the mechanisms and kinetics of phenotypic robustness of cell fate reprogramming. The occurrence of tunable switches capable of modifying the nature of cell fate reprogramming from pathological to physiological might pave the way for new therapeutic strategies to regulate reparative reprogramming in ageing and cancer.

18:45- Closing