Biology subjects

Smith, A. G.

Publications and source records attributed to Smith, A. G..

3 recordsLinked to original sources

bioRxiv2018

Genetic transformation of the dinoflagellate chloroplast

Coral reefs are some of the most important and ecologically diverse marine environments. At the base of the reef ecosystem are dinoflagellate algae, living in symbiosis with coral. Efforts to understand the relationship between alga and coral have been greatly hampered by the lack of an appropriate dinoflagellate genetic transformation technology. By making use of the plasmid-like fragmented chloroplast genome, we have introduced novel genetic material into the dinoflagellate chloroplast genome. We have shown that the introduced genes are expressed and confer the expected phenotypes. Genetically modified cultures have been grown for five months with subculturing, maintaining the introduced genes and phenotypes. This indicates that cells continue to divide after transformation and that the transformation is stable.

genetics↗

bioRxiv2017

A common molecular logic determines embryonic stem cell self-renewal and reprogramming

During differentiation and reprogramming new cell identities are generated by reconfiguration of gene regulatory networks. Here we combined automated formal reasoning with experimentation to expose the logic of network activation during induction of naive pluripotency. We find that a Boolean network architecture defined for maintenance of naive state embryonic stem cells (ESC) also explains transcription factor behaviour and potency during resetting from primed pluripotency. Computationally identified gene activation trajectories were experimentally substantiated at single cell resolution. Contingency of factor availability explains the counterintuitive observation that Klf2, which is dispensable for ESC maintenance, is required during resetting. We tested 136 predictions formulated by the dynamic network, finding a predictive accuracy of 78.7%. Finally, we show that this network explains and predicts experimental observations of somatic cell reprogramming. We conclude that a common deterministic program of gene regulation is sufficient to govern maintenance and induction of naive pluripotency. The tools exemplified here could be broadly applied to delineate dynamic networks underlying cell fate transitions.

developmental biology↗

bioRxiv2017

Microbial mutualism at a distance

The exchange of diffusive metabolites is known to control the spatial patterns formed by microbial populations, as revealed by recent studies in the laboratory. However, the matrices used, such as agarose pads, lack the structured geometry of many natural microbial habitats, including in the soil or on the surfaces of plants or animals. Here we address the important question of how such geometry may control diffusive exchanges and microbial interaction. We model mathematically mutualistic interactions within a minimal unit of structure: two growing reservoirs linked by a diffusive channel through which metabolites are exchanged. The model is applied to study a synthetic mutualism, experimentally parameterised on a model algal-bacterial co-culture. Analytical and numerical solutions of the model predict conditions for the successful establishment of remote mutualisms, and how this depends, often counterintutively, on diffusion geometry. We connect our findings to understanding complex behaviour in synthetic and naturally occurring microbial communities.

biophysics↗