Centre for Developmental and Biomedical Genetics

Many human diseases involve interactions between various cell types, tissues and organ systems that cannot readily be reproduced in the tissue culture dish. The main goal of the Centre for Developmental and Biomedical Genetics is to use non-mammalian species to model human disease processes in a whole organism context. Our approach is based on discoveries made in the past two decades that have revealed that organisms as simple as a tropical fish, fruit fly or even a worm share many cellular functions and have many genes in common with humans. By manipulating these organisms’ versions of human disease associated genes, we can establish models for a variety of debilitating diseases and exploit these to discover new therapeutic agents. In addition, we can generate pathological conditions – such as the blockage of arteries – in these simple organisms and use these to discover novel genes that underlie the corresponding human pathology. Through these approaches we aim to expand our knowledge of the molecular basis of a range of human diseases, including cardiovascular, inflammatory and neurodegenerative, giving new insights into their causes and providing new leads for their diagnosis, management and cure.

Genetic analysis of model organisms over the past twenty years has uncovered an extraordinarily high level of conservation of the regulatory pathways that control developmental and physiological processes within the meatzoa, providing remarkable new insights into the molecular basis of human congenital abnormalities and disease. The sophisticated genetic tools and techniques that are now available in Drosophila, and increasingly so in zebrafish, allow developmental and physiological processes to be analysed at the cellular and sub-cellular level. These organisms thus represent outstanding experimental models for the in vivo functional analysis of the human genome and in particular, for the elucidation of the cellular and molecular processed underlying human disease. The Centre for Developmental and Biomedical Genetics brings together cell and developmental biologists with clinician scientists, creating a distinct interdisciplinary environment for the investigation of the cellular basis of development and disease using such models. Gene discovery programmes using both forward mutation screening and gene expression profiling will be combined with chemical genetic approaches to identify novel components of developmental networks and unravel their mechanisms of action. The sophisticated techniques available in Drosophila and zebrafish for the manipulation of gene activity and the analysis of cellular behaviour at the single cell level will be used to generate models diseases associated with know human gene mutations. These models will be exploited in screens for mutations and molecules that can modify their effects, to identify novel genetic disease modulators and leads for potential new therapies. Discoveries made in flies and fish will be validated in the chick embryo and using mammalian cell cultures, including embryonic stem cells. The establishment of such a Centre within the School of Medicine and Biomedical Sciences provides a focus of expertise in the development of animal models of human disease that will stimulate the exploitation of findings from model systems in the development of novel therapies and clinical practise.