Dissecting cell and tissue mechanics of the prospective forebrain during early zebrafish development

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School

Abstract

Programme overview:

This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Project:
This study will address how mechanical forces contribute to forebrain development and will use the zebrafish embryo as a model system to investigate the affect of forces on cell and tissue shape changes, by performing live cell imaging and probing cell mechanical properties using biophysical measurements.
The project will involve cutting-edge live-cell imaging (multiphoton and diSPIM microscopy) to image processes during embryonic development on multiple levels. Quantitative force measurements such as laser ablation and force interference methods will be applied. High-end software and computational analyses will be developed for quantitative tension measurements and a mathematical model to calculate material properties will be developed.
Studying very early processes of brain development in the growing embryo will lead to a better understanding of the complexity of the adult brain and associated pathologies. It becomes increasingly clear from work on mutant zebrafish embryos associated with brain abnormalities such as cyclopia, that cell and tissue morphogenesis is impaired during early development, creating a causal link between force generated processes and disease. Given the numerous birth defects in humans, the outcomes of this study are expected to advance understanding of the causes, prevention and treatment of related diseases, including cyclocephaly, and neural tube defects including the prevalent spina bifida.
The interdisciplinary techniques as well as the areas of science covered make this project a perfect fit for the framework of the MRC strategic priorities, in particular the Applied Biomedical Technologies theme. Discoveries from this research can be a valuable starting point for industry objectives, such as developing of novel drugs and treatments tackling brain diseases. Creating a better understanding of complex disease mechanisms is therefore essential to accelerate medicine discoveries and progress advanced therapeutics such as regenerative medicine.

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