Understanding the mechanisms of mutagenesis is important for prevention and treatment of numerous diseases, most prominently cancer. Large sequencing datasets revealed a substantial number of mutational processes in recent years, many of which are poorly understood or of completely unknown aetiology. These mutational processes leave characteristic sequence patterns in the DNA, often called "mutational signatures". We use bioinformatics methods to characterise the mutational signatures with respect to different genomic features and processes in order to unravel the aetiology and mechanisms of mutagenesis. 

In this talk, I will present our results on how mutational processes might be modulated by DNA replication. We developed a linear-algebra-based method to quantify the magnitude of replication strand asymmetry of mutational signatures in individual patients, followed by detection of these signatures in early and late replicating regions. Our analysis shows that a surprisingly high proportion (more than 75 %) of mutational signatures exhibits a significant replication strand asymmetry or correlation with replication timing. However, distinct groups of signatures have distinct replication-associated properties, capturing differences in DNA repair related to replication, and how different types of DNA damage are translated into mutations during replication. These findings shed new light on the aetiology of several common but poorly explained mutational signatures, such as suggesting a novel role of replication in the mutagenesis due to 5-methylcytosine (signature 1), or supporting involvement of oxidative damage in the aetiology of a signature characteristic for oesophageal cancers (signature 17). I will conclude with our ongoing work of wet-lab validations of some of these hypotheses and usage of computational methods (such as genetic algorithms) in guiding the development of experimental protocols.

The spatial coordination of cellular differentiation enables functional organogenesis. How coordination results in specific patterns of differentiation in a robust manner is a fundamental question for all developmental systems in biology. Theoreticians such as Turing and Wolpert have proposed the importance of specific mechanisms that enable certain types of patterns to emerge, but these mechanisms are often difficult to identify in natural systems. Therefore, we have started using synthetic biology to ask whether specific mechanisms of pattern formation can be engineered into a simple cellular background. In this talk, I will show several examples of emergent spatial patterning that results from the insertion of synthetic signalling pathways and transcriptional logic into E. coli. In all cases, we use computational modelling to initially design circuits with a desired outcome, and improve the selection of biological components (DNA sub-sequences) that achieve this outcome according to a quantifiable measure. In the specific case of Turing patterns, we have yet to produce a functional system in vivo, but I will describe new analytical tools that are helping to guide the design of synthetic circuits that can produce a Turing instability.

We study the stability properties of the Eulerian mean flow generated by monochromatic surface-gravity waves propagating in a rotating frame. The wave averaged equations, also known as the Craik-Leibovich equations, govern the evolution of the mean flow. For propagating waves in a rotating frame these equations admit a steady depth-dependent base flow sometimes called the Ekman-Stokes spiral, because of its resemblance to the standard Ekman spiral. This base flow profile is controlled by two non-dimensional numbers, the Ekman number Ek and the Rossby number Ro. We show that this steady laminar velocity profile is linearly unstable above a critical Rossby number Roc(Ek). We determine the threshold Rossby number as a function of Ek using a numerical eigenvalue solver, before confirming the numerical results through asymptotic expansions in the large/low Ek limit. These were also confirmed by nonlinear simulations of the Craik-Leibovich equations. When the system is well above the linear instability threshold, Ro >> Roc, the resulting flow fluctuates chaotically. We will discuss the possible implications in an oceanographic context, as well as for laboratory experiments.

We aim to establish and experimentally test mathematical models of embryogenesis. While the foundation of this research is based on models of isolated developmental events, the ultimate challenge is to formulate and understand dynamical systems encompassing multiple stages of development and multiple levels of regulation. These range from specific chemical reactions in single cells to coordinated dynamics of multiple cells during morphogenesis. Examples of our dynamical systems models of embryogenesis – from the events in the Drosophila egg to the early stages of gastrulation – will be presented. Each of these will demonstrate what had been learned from model analysis and model-driven experiments, and what further research directions are guided by these models.

In this talk I shall describe recent work inspired by problems in cell biology, namely how the dynamics of small G-proteins underlies polarity formation. Their dynamics is such that their active membrane bound form diffuses more slowly. Hence you might expect Turing patterns. Yet how do cells form backs and fronts or single isolated patches. In understanding these questions we shall show that the key is to identify the parameter region where Turing bifurcations are sub-critical. What emerges is a unified 2-parameter bifurcation diagram containing pinned fronts, localised spots, localised patterns. This diagram appears in many canonical models such as Schnakenberg and Brusselator, as well as biologically more realistic systems. A link is also found between theories of semi-string interaction asymptotics and so-called homoclinic snaking. I will close with some remarks about relevance to root hair formation and to the importance of subcriticality in biology. 

Automatic structures are algebraic structures, such as graphs, groups
and partial orders, that can be presented by automata. By varying the 
classes of automata (e.g. finite automata, tree automata, omega-automata) 
one varies the classes of automatic structures. The class of all automatic 
structures is robust in the sense that it is closed under many natural
algebraic and model-theoretic operations.  
In this talk, we give formal definitions to 
automatic structures, motivate the study, present many examples, and
explain several fundamental theorems.  Some results in the area
are deeply connected  with algebra, additive combinatorics, set theory, 
and complexity theory. 
We then motivate and pose several important  unresolved questions in the
area.

In this talk, I will talk about the existence of global weak solutions for the compressible Navier-Stokes equations, in particular, the viscosity coefficients depend on the density. Our main contribution is to further develop renormalized techniques so that the Mellet-Vasseur type inequality is not necessary for the compactness.  This provides existence of global solutions in time, for the barotropic compressible Navier-Stokes equations, for any $\gamma>1$, in three dimensional space, with large initial data, possibly vanishing on the vacuum. This is a joint work with D. Bresch, A. Vasseur.