Spatial analysis to investigate the emergent dynamics of a cellular automaton model of tumour-immune interactions.
Abstract
Baseline T cell infiltration and the spatial distribution of T cells within a tumour has been found to be a significant indicator of patient outcomes. This observation, coupled with the increasing availability of spatially-resolved imaging data of individual cells within the tumour tissue, motivates the development of mathematical models which capture the spatial dynamics of T cells. Agent-based models allow the simulation of complex biological systems with detailed spatial resolution, and generate rich spatio-temporal datasets. In order to fully leverage the information contained within these simulated datasets, spatial statistics provide methods of analysis and insight into the biological system modelled, by quantifying inherent spatial heterogeneity within the system. We present a cellular automaton model of interactions between tumour cells and cytotoxic T cells, and an analysis of the model dynamics, considering both the temporal and spatial evolution of the system. We use the model to investigate some of the standard assumptions made in these models, to assess the suitability of the models to accurately describe tumour-immune dynamics.
13:45
2d RCFTs and 3d TQFTs
Junior Strings is a seminar series where DPhil students present topics of common interest that do not necessarily overlap with their own research area. This is primarily aimed at PhD students and post-docs but everyone is welcome.
CRISPR-based decoding of disease-associated genomic variants
Abstract
The overall goal of the Sherwood lab is to advance genomic and precision medicine applications through high-throughput, multi-disciplinary science. In a shortened talk this past autumn, I described our recent efforts using combined analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening to improve the identification of genes, coding variants, and non-coding variants whose alteration impacts serum LDL cholesterol (LDL-C) levels.
In this talk, I will discuss our emerging efforts to optimize and employ precision CRISPR techniques such as base editing and prime editing to better understand the impacts of coding and non-coding variation on serum LDL-C levels and coronary artery disease risk. This work involves the development of novel high-throughput screening platforms and computational analysis approaches that have wide applicability in dissecting complex human disease genetics.