We currently have two 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.
We adopt a ‘bench to bedside’ approach to study the basis of neuropsychiatric, neurodevelopmental and neurodegenerative disorders. Our approach is theoretically guided by the principles of precision medicine, i.e., that understanding the biology of these disorders will help develop individualised treatments for patients.
- Basic neural and behavioural biology of neuropsychiatric, neurodevelopmental, and neurodegenerative disorders.
In our basic research, we use zebrafish as a model species try to understand the biology of neuropsychiatric (eg impulsive/compulsive disorders), neurodevelopmental (eg foetal alcohol spectrum disorders), and neurodegenerative disorders (eg Alzheimer's disease). 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 behavioural abnormalities, and use a psychopharmacological approach to test our hypotheses. 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. This work is supported by grants from CAPES foundation (Brazil), Alzheimer's Research UK, and the University of Portsmouth.
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. We are involved with work at Queen Alexandra Hospital (Portsmouth) working with high-risk recreational drinkers to look at personality and genetic markers of risky drinking. This work is supported by the Economic and Social Research Council (ESRC) and the Foundation for Liver Research.
- 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). This work is currently supported by the University of Portsmouth (internal PhD research studentship).
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!