Adaptive evolution of a yeast for palm oil replacement: genotype-phenotype relationships by nanopore sequencing

The main goal of our research is to make evolutionary and genomic tools work for industry and to
improve the outcomes of fungal interactions that matter for people. Currently we are working on
Metschnikowia pulcherrima, a ubiquitous species of yeast that produces high concentrations of an oil
with properties similar to those of palm oil. Palm oil is the most commonly produced vegetable oil and
is used in a vast range of products including processed foods, cosmetics, cleaning products and
biofuels, but palm oil production is environmentally and socially deleterious. Metschnikowia
pulcherrima could provide a route to a more sustainable alternative to palm oil, but this requires
significant advancement of the capabilities of this yeast.
We are using adaptive laboratory evolution to improve the productivity and utility of Metschnikowia
pulcherrima. The aim of this project is to understand the genetic changes underlying phenotypic
changes in Metschnikowia pulcherrima when it is subjected to a series of adaptive evolution scenarios.
These scenarios are focused on improving the properties of Metschnikowia pulcherrima for industrial
exploitation, including inhibitor and fungicidal resistance, and ability to thrive in a heterogeneous
environment; the scenarios include inhibitor tolerance, temperature, microbial competition, and
substrate conversion.
The genetic changes underlying phenotypic changes in fungi are strongly linked to copy number
fluctuation, genomic restructuring, and epimutation (a heritable change that affects gene expression
without a change in DNA sequence, including base modification). Since such genetic changes are
relatively difficult to detect with standard sequencing technology, we will exploit the capacity of
nanopore sequencers (e.g. the MinION) to make very/ultra long reads and to detect base
modifications to elucidate the genetic changes in Metschnikowia pulcherrima during adaptive
evolution. Data-informed mathematical modelling will be used to enhance understanding of
evolutionary mechanisms. Although industrial utility is the focus of these adaptive evolution
experiments, the evolutionary mechanisms elucidated can additionally be used as a point of
comparison to the near relative and emerging pathogen Candida auris, the marine pathogenic yeast
Metschnikowia bicuspidata, and the biocontrol yeast Metschnikowia fructicola.
This PhD project will provide broad, multidisciplinary training encompassing yeast biology, fungal
genetics, basic molecular biology, nanopore sequencing, bioinformatics, and mathematical modelling
of genetic changes. The project is sponsored by Oxford Nanopore Technologies (ONT). In addition to
regular update meetings with ONT staff and technical support from ONT, the studentship will
incorporate a placement of at least three months with ONT.