Mathematical Biology and Ecology Seminar

Please note that the list below only shows forthcoming events, which may not include regular events that have not yet been entered for the forthcoming term. Please see the past events page for a list of all seminar series that the department has on offer.

Past events in this series
Today
14:00
Abstract

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.

  • Mathematical Biology and Ecology Seminar
22 November 2019
14:00
Abstract

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.

  • Mathematical Biology and Ecology Seminar
29 November 2019
14:00
Abstract

When cells migrate through constricting pores, there is an increase in DNA damage and mutations. Experimental observations show that this breakage is not due to mechanical stress. I present an elastic-fluid model of the cell nucleus, coupled to kinetics of DNA breakage and repair proposing a mechanism by which nuclear deformation can lead to DNA damage. I show that segregation of soluble repair factors from the chromatin during migration leads to a decrease in the repair rate and an accumulation of damage that is sufficient to account for the extent of DNA damage observed experimentally.

In the second part I will talk about how some types of cancer cells grow uncontrollably. Telomeres are DNA caps on the end of chromosomes and are shortened during each cell division. Tumour cells elongate their telomeres so that unlike healthy cells they do not undergo programmed death. I will show how some types of cancer cells can control microphase separation to form micelle-like structures with telomeres in the cores. This clustering of telomeres is a crucial step in the elongation process and understanding the physics involved can help us understand how this process could be disrupted.

  • Mathematical Biology and Ecology Seminar
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