Centre for Developmental and Biomedical Genetics

Lead Research Organisation: University of Sheffield
Department Name: Medicine and Biomedical Science

Abstract

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.

Technical Summary

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.
 
Description Use of animals in Medical Research
Geographic Reach Europe 
Policy Influence Type Membership of a guidance committee
 
Description Catalyst Article (CP) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact A 1500 word article in Catalyst, a science magazine, describing the use of zebrafish in medical research at the CDBG in Sheffield.

School leaving pupils will be more aware of the use of alternative model organisms and the ability to research human diseases in models other than mice and rats. It also raises the profile of Sheffield as a University carrying out targeted research into human diseases.
Year(s) Of Engagement Activity 2009
 
Description Departmental Open Days 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Regular Departmental Open Days for prospective students and parents. Visitors are shown around the Department, including demonstrations of research work. Feedback is very positive.

Recruitment of students.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010,2011,2012,2013,2014
 
Description Molecular Biology Pratical (FVE EJ) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact Demonstration to A level students, molecular biology practical: isolating human DNA.

NA.
Year(s) Of Engagement Activity 2010
 
Description Science Week presentations (FVE EJ) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact Presentation of Biochemical techniques: chromatography.
Assistance in Using animals to model neuropathological diseases.

NA
Year(s) Of Engagement Activity 2010