"Stochastic epigenome systems under inflammatory signals and its application to study vivo nucleosome accessibility"
In cellular immune responses, inflammatory ligands activate signal-dependent transcription factors (SDTFs), which can display complex temporal profiles. SDTFs are central effectors for inflammatory gene expression, and hence they serve a critical role in immune system. The information contained in SDTF signals must also be decoded by the epigenome to allow controlled plasticity in cellular epigenetic states in response to environmental encounters. The mechanisms and biophysical principles that generate distinct epigenomes in response to different SDTF signaling remain unclear. Here, we develop and analyze stochastic models of nucleosome accessibility to study how SDTF signals alter the epigenome dynamics. Interestingly the response of our epigenome model to SDTF signals helps us to predict the system parameters of genome-scale nucleosome in vivo. On the genome-scale, the relation between the SDTF binding location and nucleosome accessibility plays a role of a parameter predictor since the epigenome dynamics depends on SDTF binding sites differently under various parameter regimes. We could compare our numerical results to experimental measurements to test our prediction. Our work proposes a systematic framework that allows a predictive understanding in vivo nucleosome accessibility.
Johannes Gutenberg Universitat Mainz
"Autophosphorylation as a source of multistability."
Src kinases, which have many functions in cell biology, are known to undergo autophosphorylation in trans. This means that the phosphorylation of a site on the kinase is catalysed by another molecule of the same enzyme. This type of phosphorylation can lead to new phenomena. The usual model of the phosphorylation of a protein on a single site is known to admit only one steady state. In the work reported on here it is proved that in the case of a site which is subject to autophosphorylation there can be more than one stable steady state. Thus a substance of this type can serve as a switch. Src kinases such as Lck, which is involved in many processes in lymphocytes, have two tyrosine phosphorylation sites but a form of Lck in which one of these sites (Y394) has been knocked out has been studied experimentally. It represents a known substance to which the model we have studied is applicable. This work is intended as a step towards a better understanding of the regulation of the activation of Lck, and thus of the function of lymphocytes. This type of insight has the potential to improve cancer immunotherapy.
University of Alberta
"Non-local models for cellular adhesion"
Cellular adhesion is one of the most important interaction forces between cells and other tissue components. In 2006, Armstrong, Painter and Sherratt introduced a non-local PDE model for cellular adhesion, which was able to describe known experimental results on cell sorting and cancer growth. Since then, this model has been the focus of applications and analysis. The analysis becomes challenging through non-local cell-cell interaction and interactions with boundaries. In this talk I will present theoretical results of the adhesion model, such as a random walk derivation, biologically realistic boundary conditions, pattern formation and results on local and global existence of solutions.