As the result of recent successes in the sequencing of DNA extracted from environmental samples, we now find ourselves awash with genomic sequence information. This includes enormous numbers of near complete genomes for archaeal and bacterial lineages that have never been isolated, cultured, or imaged.
To infer the cellular architecture of these previously unstudied organisms, in this project the student will aim to combine phylogenetics, informatics and machine learning to define rules that can be used to predict a cell’s shape and membrane architecture from its genome. It is hoped that this will identify key factors that determine archaeal cell shape and membrane organisation, along with key markers of cell structure. Inferences will then be tested using a combination of expansion microscopy and electron microscopy.
To begin, the student will aim to define ways of using genomic sequence data alone to explain why the related archaea, Sulfolobus and Ignicoccus, have one and two membranes, respectively. The information gained from this initial analysis will then be used to try and infer the structure of cells growing in mixed microbial communities that include Asagrd archaea, together with novel lineages of bacteria and archaea.
If inferences prove correct, the student will attempt to roll out their model to predict the structures of all bacteria and archaea across the tree of life.
References
On the Archaeal Origins of Eukaryotes and the Challenges of Inferring Phenotype from Genotype
Trends in Cell Biology 26(7): 476-485 (2016)
A genome-wide atlas of human cell morphology
Nature Methods 22(3): 621-633 (2025)
A functional genomic analysis of cell morphology using RNA interference
Journal of Biology 2(4): (2003)
The Selective Value of Bacterial Shape
Microbiology and Molecular Biology Reviews 70(3): 660-703 (2006)
Accurate structure prediction of biomolecular interactions with AlphaFold 3
Nature 630(8016): 493-500 (2024)