Biology subjects

Weston, B. R.

Publications and source records attributed to Weston, B. R..

2 recordsLinked to original sources

bioRxiv2022

Modeling the Cell Cycle Response to Carbon and Nitrogen deprivation in Caulobacter Populations

Caulobacter crescentus inhabits a wide range of aquatic ecosystems, including environments with poor nutrients. It undergoes an asymmetrical cell division cycle, generating a pair of daughter cells with distinct motility and replicative potentials. Caulobacter populations have the flexibility to save energy by halting chromosome replication and reduce intraspecific competition by settling in different places in environments. The control mechanisms underlying Caulobacter cell development have been well studied under nutrient-rich conditions, however, its mechanism of response to stressful changes is not fully understood. Here we present a mathematical model to analyze the starvation responses in Caulobacter. We investigate several known starvation signaling pathways to study how these pathways influence cell cycle development and explain experimental observations of starved Caulobacter populations. We also apply a new parameterization strategy to mathematical modeling of biological systems, whose diverse communities have to be robust with many parameter variations, while still having accurate control to maintain regular cell cycle dynamics. Our model demonstrates that the guanine-based second messenger, c-di-GMP (cdG), plays important roles to immediately arrest the cell cycle of Caulobacter under nutrient deprivation; however, it is not sufficient to cause the robust arrest. Our model suggests there should be unknown pathway(s) reducing the levels of CtrA under starvation condition, which results in a significant delay in cytokinesis of starved stalked Caulobacter cells.

bioinformatics↗

bioRxiv2020

Elucidation of tumor-stromal heterogeneity and the ligand-receptor interactome by single cell transcriptomics in real-world pancreatic cancer biopsies

Precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC) are imperative for improving disease outcomes. However, the long-term fidelity of recently deployed ex vivo preclinical platforms, such as patient-derived organoids (PDOs) remains unknown. Through single-cell RNA sequencing (scRNA-seq), we identify substantial transcriptomic evolution of PDOs propagated from the parental tumor, which may alter predicted drug sensitivity. In contrast, scRNA-seq is readily applicable to limited biopsies from human primary and metastatic PDAC and identifies most cancers as being an admixture of previously described epithelial transcriptomic subtypes. Integrative analyses of our data provide an in-depth characterization of the heterogeneity within the tumor microenvironment, including cancer-associated fibroblast (CAF) subclasses, and predicts for a multitude of ligand-receptor interactions, revealing potential targets for immunotherapy approaches. While PDOs continue to enable prospective therapeutic prediction, our analysis also demonstrates the complementarity of using orthogonal de novo biopsies from PDAC patients paired with scRNA-seq to inform clinical decision-making. Statement of SignificanceThe application of single-cell RNA sequencing to diagnostic pancreatic cancer biopsies provides in-depth transcriptomic characterization of the tumor epithelium and microenvironment, while minimizing potential artifacts introduced by an intervening ex vivo passaging step. Thus, this approach can complement the use of patient-derived organoids in implementing precision oncology.

cancer biology↗