Biology subjects

Richards, R.

Publications and source records attributed to Richards, R..

3 recordsLinked to original sources

bioRxiv2018

4D imaging and analysis of multicellular tumour spheroid cell migration and invasion

Studying and characterising tumour cell migration is critical for understanding disease progression and for assessing drug efficacy. Whilst tumour cell migration occurs fundamentally in 3 spatial dimensions (3D), for practical reasons, most migration studies to date have performed analysis in 2D. Here we imaged live multicellular tumour spheroids with lightsheet fluorescence microscopy to determine cellular migration and invasion in 3D over time (4D). We focused on glioblastoma, which are aggressive brain tumours, where cell invasion into the surrounding normal brain remains a major clinical challenge. We developed a workflow for analysing complex 3D cell movement, taking into account migration within the spheroid as well as invasion into the surrounding matrix. This provided metrics characterising cell motion, which we used to evaluate the efficacy of chemother-apeutics on invasion. These rich datasets open avenues for further studies on drug efficacy, microenvironment composition, as well as collective cell migration and metastatic potential.

cell biology↗

bioRxiv2017

Fibroblasts from metastatic sites induce broad-spectrum drug desensitization via modulation of mitochondrial priming

Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor micro-environment. Using a large-scale co-culture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not cell intrinsic, but rather a product of tumor-fibroblast interactions. Additionally, we find that fibroblast cells influence tumor drug response in two distinct and divergent manners, which were predicable based on the anatomical origin from which the fibroblasts were harvested. These divergent phenotypes result from modulation of \"mitochondrial priming\" of tumor cells, caused by secretion of inflammatory cytokines, such as IL6 and IL8, from stromal cells.

cancer biology↗

bioRxiv2017

Estimating environmental suitability

Author statementJD proposed the model, JD and RR wrote the code and performed the analysis, JD wrote the first draft of the manuscript, and all authors contributed substantially to revisions.\n\nAbstractMethods for modeling species, distributions in nature are typically evaluated empirically with respect to data from observations of species occurrence and, occasionally, absence at surveyed locations. Such models are relatively \"theory-free\". In contrast, theories for explaining species, distributions draw on concepts like fitness, niche, and environmental suitability. This paper proposes that environmental suitability be defined as the conditional probability of occurrence of a species given the state of the environment at a location. Any quantity that is proportional to this probability is a measure of relative suitability and the support of this probability is the niche. This formulation suggests new methods for presence-background modeling of species distributions that unify statistical methodology with the conceptual framework of niche theory. One method, the plug-and-play approach, is introduced for the first time. Variations on the plug-and-play approach were studied with respect to their numerical performance on 106 species from an exhaustively sampled presence/absence survey of vegetation in the Canton of Vaud, Switzerland. Additionally, we looked at the robustness of these methods to the presence of irrelevant information and sample size. Although irrelevant variables eroded the predictive performance of all methods, these methods were found to be both numerically and statistically robust.

ecology↗