PhD Projects

 

I have PhD projects available including:















Phenotypic plasticity and maternal effects in spatially varying environments


Phenotypic plasticity is the ability of an organism to adapt its phenotype - its observable characteristics, such as body size  or growth rate - to its environment during its lifetime. Maternal effects can be described as the effects of a mother's phenotype on her offspring's phenotype through pathways other than direct genetic transmission, for example through epigenetic changes in the DNA, resource transmission in the womb, or behavioural responses to offspring behaviour. The aim of this project is to explore the effect of variable habitat quality on the evolution of phenotypic plasticity and maternal effects so as to understand better how populations adapt to spatially varying environments.

If you are interested in one of these projects or in finding out about the possibility of a PhD project in one of my other research areas please email me at r.b.hoyle@soton.ac.uk

To apply for a PhD please visit our application page www.southampton.ac.uk/maths/postgraduate/research_degrees/apply.page.

By Mgiganteus CC BY-SA 3.0 via Wikimedia Commons

Biofilm on stainless steel (public domain image)

Modelling biofilm dynamics


Biofilms are communities of bacteria and other small organisms that form a spatial structure like the black slime you get in taps and garden hoses. They can have important implications for health in some circumstances, for example by causing disease or by fouling medical implants. People with cystic fibrosis are often infected by the bacterium Pseudomonas aeruginosa. In order to survive, Pseudomonas aeruginosa needs iron, which it imports by secreting molecules called siderophores that bind the iron and then reabsorbing them. Each bacterium can absorb siderophores secreted by any other bacterium, and in fact there are mutant strains of P. aeruginosa that `cheat’ by absorbing siderophores, but not producing any. The cheats gain an advantage over the cooperative wild-type bacteria, because they don’t put energy into siderophore production and so are able to outcompete the wild-type locally as long as enough wild types remain to produce sufficient siderophores for everyone. This cooperator-cheat dynamics may lead to more persistent P. aeruginosa infections.

When P. aeruginosa cooperator and cheat strains are grown together in the lab, segregation of the two types leads to spatial patterns. This project will use mathematical and computational modelling to investigate the spatial patterning in order to understand its causes and potential consequences for bacterial persistence. The models that we develop will span multiple scales from the scale of an individual P. aeruginosa bacterium up to the level of a bacterial colony on which pattern formation is observed, incorporating not only exchanges of chemicals - such as siderophores and nutrients - between the bacteria and their environment, but also physical interactions with their surrounding medium and substrate resulting from effects such as colony growth and fluid flow. The theoretical work will develop in close cooperation with biologists Dr Jose Jimenez and Dr Alexandra Penn who have studied this system in the lab.

Modelling the effect of maternal protein restriction diet on neural stem cell differentiation and brain

development in mice

In mice the differentiation of neural stem cells is disrupted in the offspring by a low protein maternal diet: the number of neural stem cells is initially decreased, but then differentiation proceeds at greater rate compared to mice whose mothers are fed normally. When the low protein diet persists through pregnancy the final number of neurons in the offspring brains is normal, whereas when the diet is poor only during the very early phase of pregnancy the offspring end up with more neurons than normal. The offspring whose mothers were fed a low protein diet at some stage of the pregnancy exhibit `hyperactive’ behaviour as adults, but the effect is only statistically significant for those whose mothers received the diet only in early pregnancy. These mice also show a variety of other abnormal behavioural responses.


During differentiation the cells that will become neurons move through different layers of cells. Experimental data has been collected from two different locations: the cortex and the ganglionic eminences, and at 3 different timepoints during gestation on the pathway of neuronal differentiation.


In this project we will model how the differentiation of neural stem cells in mice responds to diet, predicting the numbers of cells at each stage of differentiation and fitting the models to experimental data already collected from the cortex and the ganglionic eminences at different time points. The modelling will proceed in closer cooperation with experimentalist Dr Sandrine Willaime-Morawek in whose lab the data was collected.  We will use the model to understand better how altered rates of differentiation at each stage lead to different numbers of neurons in the neonate mouse brain.

Experimental evidence shows that when mouse mothers are fed a low protein diet in pregnancy their offspring show abnormal neuronal development and behaviour. The protein in the restricted diet was half the amount in a normal diet, but still remains in the normal range so this was a mild nutritional challenge rather than starvation. Surprisingly the abnormalities were worse if the mother only received the low protein diet in the very early phase of her pregnancy before the embryo implants into the uterine wall and was fed normally after that.


It is possible that development of the human brain is also adversely affected by inadequate maternal diet during pregnancy. Children born to mothers who were in the early part of their pregnancy during the Dutch winter famine (1944-45) in World War II showed an increased risk of schizophrenia and other neurological disorders. There is also evidence for an increased risk of schizophrenia in urban cohorts that were in gestation during the Great Leap Forward Famine in China (1959-61).

A confocal  microscopic image of a cluster of neural stem cells

Further information