We currently have a number of fully-funded PhD studentships available, either in my lab, or working indirectly with my lab. Click on the project-descriptions below to learn more and to apply directly!
These two studentships are funded by the University of Portsmouth, and will start in Sept 2020. They are part of a collaboration between my lab and the group of Professor Darek Goreki, and will be concentrating on the developmental disorder Duchenne's Muscular Dystrophy, and related neurodevelopmental conditions:
1. DMD gene mutations result in Duchenne Muscular Dystrophy, which gave the gene its name. Using a genetically altered zebrafish line, this project will investigate the developmental effects of DMD mutations to establish whether an early treatment could prevent irreversible damage. Importantly, somatic DMD mutations have been associated with aggressive cancers. Given the commonalities in development and oncogensis, tumour formation might be a novel but related aspect of DMD gene dysfunction. The unique multi-omics data already available to us will be studied and the bioinformatics integration performed in collaboration with the Han Lab at the Milner Institute, Cambridge. The functional impact of DMD gene in oncogenesis will be studied in cancer cells, in collaboration with the Sicinski Cell Cycle Machinery in Development and Cancer lab at Harvard. Unravelling novel mechanisms triggered by DMD mutations in cancer might help developing new diagnostic and therapeutic tools for this condition.
2. Mutations in the DMD gene cause the progressive neuromuscular disorder and also molecular alterations in neurons and astrocytes, which could explain the cognitive deficits commonly seen in Duchenne patients. This project will exploit animal models, distinguished by specific DMD gene mutations, in combination with advanced omics analyses (collaboration with the Proteome Exploration Laboratory, CalTech) to identify alterations of specific pathways and interaction networks and then confirm their impact using molecular methods (collaboration with Leiden and Southampton universities) and advanced microscopy (Portsmouth Zeiss Global Centre). In parallel, behavioural analyses in dystrophic mice and zebrafish will be performed. Using the latter model, individual brain cells will be visualised in vivo using the light sheet microscope (in collaboration with Exeter University). Subsequently, alterations found in these animal models will be compared with patients’ phenotypes.
3. Understanding others’ mental states is key to navigating a complex social world. However, some individuals, including those with developmental disorders such as autism, find this difficult. This research will use behavioural and physiological measures to investigate how children develop these abilities and whether the same mechanisms are necessary for understanding emotions versus thoughts. Further, it will identify whether there are links between our ability to actively calculate another’s mental state and our tendency to experience contagion from their state without being aware it is occurring. By identifying the mechanisms underlying mental state understanding, we can better understand situations in which this can be impaired.
This studentship is fully funded by the BBSRC, and is part of the South Coast Biosciences (SoCoBio) initiative, and will be based at Portsmouth in the Brain an Behaviour Lab, but co-supervised by Dr J. Arjuna Ratnayaka at the University of Southampton Medical school. If you are interested in this, please see the How to Apply section of the SoCoBio website. PLEASE NOTE, THIS SCHEME IS FOR UK/EU STUDENTS ONLY.
4. With the gap between lifespan and healthspan a major societal challenge, it is critical that we understand the biological processes underlying the healthy ageing process. Two issues associated with ageing are: (1) decline in working memory; and (2) decline in visual ability. We know they are linked owing to several critical shared features, such as accumulation of amyloid beta (Aβ) in the central nervous system. Working memory deficits in older adults is related to degradation in the control of attentional processes, resulting from reduced ability to suppress task-irrelevant information. Visual field deficits result from relatively well-characterised structural and physiological changes in the ageing eye. Critically, what is not presently known is what, if any, are the shared effects of ageing on cognitive and visual field function at the behavioural, neural and molecular level. This interdisciplinary programme of work will comprise cross-sectional behavioural testing across the lifespan of wild-type and genetically altered zebrafish in the Parker Laboratory, coupled with molecular characterisation of the visual/nervous system in the Ratnayaka laboratory. Cognitive tasks will include several well-characterised tests of working memory in zebrafish. With our industry collaborator (Zantiks ltd.), we will develop completely novel visual field tests to examine the ontogeny of visual field processing in the ageing zebrafish. We will then characterise patterns of age-associated synaptic loss in the eye and brain to correlate with behavioural function using pre- (synaptophysin), and post- (PSD-95) synaptic markers.
We adopt a ‘bench to bedside’ approach to study the basis of compulsive behavioural disorders. In our basic research, we use zebrafish as a model species try to understand the biology of compulsive disorders. In particular, we want to understand more about the interaction between molecular (genetic/epigenetic) and environmental (e.g., stress) factors that cause compulsive behaviours, and the associated neural circuits, to manifest. Our approach is theoretically guided by the principles of precision medicine, i.e., that understanding the biology of neuropsychiatric conditions will help develop individualised treatments for patients. Our work involves significant amounts of method development, owing to the paucity of validated, reliable measure in zebrafish. We also carry out translational research in humans, in particular looking at the interactions of impulsivity, risk-taking (personality) and (environmental) stress on alcohol use and misuse. In our applied research, we translate our findings in the laboratory to test questions relating to compulsive disorders, such as addiction and relapse (in humans) and stereotypic behaviours in domestic, farm and laboratory animals.
- Basic neural and behavioural biology of impulsive/compulsive disorders.
In our basic research, we use zebrafish as a model species try to understand the biology of compulsive disorders. We exploit recent developments in behavioural testing of adult zebrafish (many pioneered during Matt Parker's time working at Queen Mary University of London) to study gene x environment interactions in the development of impulsive behaviour. We also have developed behavioural tools that allow for fast effective screening of adult fish for learning and memory. Our goal in our zebrafish work is to understand the behavioural biology of the species in order to use it to its full capacity as a model in behavioural neuroscience.
We are interested in the interactions between impulsivity, risk-taking (personality) and (environmental) stress on alcohol use and misuse. In particular, we have found that healthy individuals that are categorised as 'risk-takers' (through psychometric tests) are more likely to crave and drink more alcohol when they experience stress. We are looking into the mechanisms that underlie this propensity, and how being a 'low risk taker' might provide resilience against stress-induced drinking.
- Compulsive/stereotypic behaviour in captive/domestic animals
We have been involved for some time in the study of compulsive stereotypic behavioural patterns in captive/domestic/laboratory animals. We are interested in the development of stereotypic behaviour, including why some animals are more at risk, and how environmental conditions affect some animals in this manner. Our research has suggested that these behaviours may manifest as a result of restrictive environmental conditions and alterations in ascending dopamine pathways (e.g., see this review).
Our approach is theoretically guided by the principle that understanding the biology of neuropsychiatric conditions will help develop more effective treatments for patients.
We are always interested in hearing from potential PhD or MRes students, and have a variety of projects available.
Please don't hesitate to contact us if you have a great idea for a project that fits with our interests!