Functional genomics for understanding behaviour and learning in a single-celled brainless blob, the slime mould Physarum polycephalum

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Evolutionary biologists have long been intrigued by the question of how seemingly complex behaviour could come about by simple rules and processes. A fascinating model system for addressing these questions is the slime mould Physarum polycephalum, a single-celled evolutionarily ancient eukaryotic organism that can spend long periods of its life cycle as a large amorphous blob called a plasmodium. The plasmodium contains millions of nuclei and an extensive pulsating cytoplasmic network that allows it to rapidly change shape and move across its substrate on the search for food and shelter. This motility behaviour can be affected by environmental stimuli, and research has suggested that the plasmodium is capable of decision making, learning and problem solving [1], famously finding the shortest path through a maze [2] (https://www.youtube.com/watch?v=F3z_mdaQ5ac)! While the plasmodium of Physarum polycephalum has been used as a model organism for cell motility, behaviour and learning for a long time, the functional genetic mechanisms responsible for producing these remarkable properties and behaviours are unknown. The recently published draft genome of Physarum has provided an initial survey of the genetic repertoire of the organism and has opened a broad suite of avenues for investigating the mechanics of gene expression and genome organisation underpinning behaviour across the plasmodium [3]. This project will develop key insights into the orchestration of fundamental genome dynamics to generate behaviour in Physarum and define novel mechanistic models for the evolutionary origin of cellular behaviour, communication and learning. Controlled experimental trials will be combined with high-throughput sequencing to examine functional responses (i.e., changes in gene expression and/or epigenetic changes in genome organisation) of the plasmodium to environmental stimuli and problem-solving situations. The key questions to be addressed are: 1) what genes are involved in behavioural changes and how are they organised in the genome?; 2) how do functional responses vary spatially among nuclei within the plasmodium?; and 3) is there an epigenetic component to adaptive behaviour?Physarum polycephalum is an intriguing organism that is simple to maintain in the lab. You will gain experience in initiating and maintaining live slime mould cultures and designing and carrying out experimental trials under controlled conditions. You will further be exposed to developing optimised lab protocols for DNA and RNA extraction suitable for high-throughput sequencing approaches such as Illumina or Oxford NanoPore sequencing. A large part of the project will involve bioinformatics processing of sequencing data, including genome alignment, differential gene expression, physiological pathway and network analysis and exploration of genome organisation. Full bioinformatics training will be provided.[1] Shirakawa, T., Gunji, Y.P. and Miyake, Y., 2011. An associative learning experiment using the plasmodium of Physarum polycephalum. Nano communication networks, 2(2-3), pp.99-105.[2] Nakagaki, T., Yamada, H. and Tóth, Á., 2000. Intelligence: Maze-solving by an amoeboid organism. Nature, 407(6803), p.470.[3] Schaap, P., Barrantes, I., Minx, P., Sasaki, N., Anderson, R.W., Bénard, M., Biggar, K.K., Buchler, N.E., Bundschuh, R., Chen, X. and Fronick, C., 2015. The Physarum polycephalum genome reveals extensive use of prokaryotic two-component and metazoan-type tyrosine kinase signaling. Genome biology and evolution, 8(1), pp.109-125