Self-organisation of heterogeneous collectives across scales:
Self-organisation of heterogeneous collectives across scales:
from intracellular phase separation to cancer biology
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Modelling phenotypic heterogeneity in solid tumours
Modelling phenotypic heterogeneity in solid tumours
In the past few decades, there has been a major shift in our understanding of cancer. The development of new technologies, such as single-cell sequencing, has showcased the complex and dynamic composition of tumours, where cancerous and non-cancerous cells with different genotypes and/or phenotypes can coexist. Such intra-tumour heterogeneity and its dynamic nature constitute a major challenge in the design of effective treatment strategies.
With my research, I am interested in the development and analysis of mathematical models -- specifically structured-population models -- that can offer novel biological insight into the driving forces of intra-tumour heterogeneity and how this contributes to the emergent tumour growth and treatment dynamics.
In a series of publications, I have contributed to unravelling how spatiotemporal variability in oxygen levels contributes to tumorigenesis by promoting heterogeneity whether influencing the cell-cycle or cancer stemness.
Self-organised patterning in migrating multicellular communities
Self-organised patterning in migrating multicellular communities
Collective cell migration is ubiquitous amongst cell groups and of great importance in tissue development and disease, such as cancer. Despite the central role of collective migration in biology, several open questions remain regarding how and to what extent cells integrate biochemical and biophysical signals to allow robust and organised group migration.
While standard theoretical frameworks, such as the Keller-Segel model, have been successful in describing cell physical interactions between cells are neglected. As a result, cells can be treated like biased gas molecules, which independently respond to chemical cues.
This simplification works surprisingly well in low-density populations, where cells move relatively freely. However, in many biologically relevant situations, such as during embryonic development, wound healing, and tumour invasion, where cells organise and migrate in densely packed groups.
The organisation of densely packed migrating cell populations is the focus of an interdisciplinary study in collaboration with Chubb's lab (UCL). By combining experimental data with Dictyostelium amoebae and mathematical modelling, we demonstrate that cell groups behave as active droplets and that the emergent material properties of the group control the spatial organisation and patterning of the colonies (see videos).
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