Biology subjects

Smith, H.

Publications and source records attributed to Smith, H..

4 recordsLinked to original sources

bioRxiv2018

Interactome comparison of human embryonic stem cell lines with the inner cell mass and trophectoderm

Human embryonic stem cells (hESCs) derived from the pluripotent Inner cell mass (ICM) of the blastocyst are fundamental tools for understanding human development, yet are not identical to their tissue of origin. To investigate this divergence we compared the transcriptomes of genetically paired ICM and trophectoderm (TE) samples with three hESC lines: MAN1, HUES3 and HUES7 at similar passage. We generated inferred interactome networks using transcriptomic data unique to the ICM or TE, and defined a hierarchy of modules (highly connected regions with shared function). We compared network properties and the modular hierarchy and show that the three hESCs had limited overlap with ICM specific transcriptome (6%-12%). However this overlap was enriched for network properties related to transcriptional activity in ICM (p=0.016); greatest in MAN1 compared to HUES3 (p=0.048) or HUES7 (p=0.012). The hierarchy of modules in the ICM interactome contained a greater proportion of MAN1 specific gene expression (46%) compared to HUES3 (28%) and HUES7 (25%) (p=9.0x10-4). These findings show that traditional methods based on transcriptome overlap are not sufficient to identify divergence of hESCs from ICM. Our approach also provides a valuable approach to the quantification of differences between hESC lines. And Manchester Academic Health Sciences Centre

developmental biology↗

bioRxiv2018

An optimized method for the isolation and the molecular characterization of cerebral microvessels in vivo

The molecular characterization of cerebral microvessels in experimental disease models has been hindered by the lack of a standardized method to reproducibly isolate intact cerebral microvessels, with consistent cellular compositions, and without the use of enzymatic digestion, which causes undesirable molecular and metabolic changes. Herein, we describe an optimized method for microvessel isolation from mouse brain cortex, which yields microvessel fragments (diameter <50 m, 89.3% 3-5 m) with consistent populations of discrete blood-brain barrier components (endothelial cells, pericytes, and astrocyte end feet), retaining high RNA integrity and protein postranslational modifications (e.g. phosphorylation). We demonstrate that this method allows the quantification of changes in gene expression in a disease model (stroke) and the activation of signalling pathways in mice subjected to drug administration. We also describe the isolation of genomic DNA and bisulfite treatment for the assessment of DNA methylation, as well as the optimization of chromatin extraction and shearing from cortical microvessels. Therefore, this protocol will be of great use to improve the understanding of the molecular mechanisms governing cerebrovascular dysfunction, which may help the development of novel therapies for stroke and other neurodegenerative diseases.

neuroscience↗

bioRxiv2017

Universal Scaling in Biochemical Networks

The application of network science to biology has advanced our understanding of the metabolism of individual organisms and the organization of ecosystems but has scarcely been applied to life at a planetary scale. To characterize planetary-scale biochemistry, we constructed biochemical networks using a global database of 28,146 annotated genomes and metagenomes, and 8,658 cataloged biochemical reactions. We uncover scaling laws governing biochemical diversity and network structure shared across levels of organization from individuals to ecosystems, to the biosphere as a whole. Comparing real biochemical networks to random chemical networks reveals the observed biological scaling is not solely a product of the biochemistry shared across life on Earth. Instead, it emerges due to how the global inventory of biochemical reactions is partitioned into individuals. We show the three domains of life are topologically distinguishable, with > 80% accuracy in predicting evolutionary domain based on biochemical network size and average topology. Taken together our results point to a deeper level of organization in biochemical networks than what has been understood so far.

systems biology↗

bioRxiv2017

Tragedy Of The Commons In The Chemostat

We present a proof of principle for the phenomenon of the tragedy of the commons that is at the center of many theories on the evolution of cooperation. We establish the tragedy in the context of a general chemostat model with two species, the cooperator and the cheater. Both species have the same growth rate function and yield constant, but the cooperator allocates a portion of the nutrient uptake towards the production of a public good -the \"Commons\" in the Tragedy-which is needed to digest the externally supplied nutrient. The cheater on the other hand does not produce this enzyme, and allocates all nutrient uptake towards its own growth. We prove that when the cheater is present initially, both the cooperator and the cheater will eventually go extinct, hereby confirming the occurrence of the tragedy. We also show that without the cheater, the cooperator can survive indefinitely, provided that at least a low level of public good or processed nutrient is available initially. Our results provide a predictive framework for the analysis of cooperator-cheater dynamics in a powerful model system of experimental evolution.

evolutionary biology↗