The NC3Rs (National Centre for the Replacement Refinement & Reduction of Animals in Research) is a UK-based scientific organisation that works with the research community to replace, refine, and reduce the use of animals in research and testing. These awards are two out of only 10 NC3Rs PhD studentships awarded nationally to embed the 3Rs in the development of the next generation of researchers.
Zebrafish models of Major Depressive Disorder as a replacement for rodent models
The project 'Zebrafish models of Major Depressive Disorder as a replacement for rodent models' is a collaboration between Professor Robert Hindges from the Centre for Developmental Neurobiology and Professor Gerome Breen from the Social Genetic and Developmental Psychiatry Centre. This project aims to establish and disseminate the zebrafish model as an alternative to mice to study the genetic basis for Major Depressive Disorder (MDD).
The group will use novel genome editing techniques to manipulate the genome of zebrafish. Zebrafish have a highly similar genome to humans, with conserved neurotransmitter pathways and brain areas. These similarities make them suitable as subjects for testing such as behavioural assays and functional brain imaging. Furthermore, zebrafish can be used for a high-throughput drug screen, expediting the chance of making a significant advance in the search for novel therapies.
This project will create zebrafish mutant lines to study candidate genes that have been identified through genome-wide association studies. They will then validate the roles of these genes through an established assessment pipeline. Additionally, this project will determine some of the relevant biochemical markers in depression and identify potential new compounds suitable for MDD treatments.
I am grateful to the NC3Rs for this special award, which will allow us to train a new researcher and study a variety of candidate risk genes for Major Depressive Disorder. Zebrafish larvae are an excellent preclinical model that allow high-throughput approaches in line with the 3Rs and we are excited to embark on this project.”– Professor Robert Hindges, the Principal Investigator of this study
Potential students are encouraged to enquire about this project directly to Professor Hindges via email.
Mapping mitochondrial contact sites during neuronal ageing and neurodegeneration in Drosophila
Dr Alessio Vagnoni from the Department of Basic and Clinical Neuroscience will be collaborating with Dr Frank Hirth on 'Mapping mitochondrial contact sites during neuronal ageing and neurodegeneration in Drosophila'. This project will use fruit flies to study the contact between mitochondria and other organelles in ageing and neurodegeneration.
The project builds on novel transgenic animals previously generated by the Vagnoni Group, to study the mitochondrial-endoplasmic reticulum contact. The new project will develop and validate genetically encoded probes to analyse the associations between mitochondria and other organelles, specifically the lysosomes and the peroxisomes. Using super-resolution microscopy, the scientists will measure these contacts in healthy and diseased ageing models (including Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis).
The Drosophila models resulting from this project will be crucial for ageing research. A collaborative network has been developed to maximise the use of this technology, with the goal of reducing the use of mice. This technology will also provide an alternative to the time-consuming and high-cost use of electron microscopy, which is currently the gold standard to study mitochondrial contact.
I am delighted to receive this award to build capacity on mitochondrial research and to continue my association with the NC3Rs through the development of new Drosophila models and training of new early career scientists”– Dr Alessio Vagnoni, the Principal Investigator of this study