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Easy and rapid generation of light-emitting somatic-transgenic mice to monitor specific disease states and to screen effective drugs

Objective

For decades, researchers have used small mammals to study the underlying processes of human disease and potential therapies for such ailments. Current strategies for measuring disease progression and/or drug effect usually involve groups of animals being killed at multiple time points for post-mortem tissue analysis. Recently, transgenic strains of mice have been created in which light-emitting luciferase is produced when a disease-specific pathway is switched on or off. High-sensitivity cameras are used to follow the profile of light emission in individual animals during disease induction/treatment, thus avoiding serial culling. However generation of transgenic mice is time-consuming, expensive, and costly in terms of animal usage. A major problem is that every tissue in the mouse may emit light, so
organ-specific effects are difficult to discern. This research programme describes the development of a process of generating light-emitting somatic-transgenic rodents by gene transfer in neonates or in utero. This permits the production of mice
containing bespoke biosensors and avoids the lengthy process of production of germline transgenics. Crucially, specific organs and tissues can be targeted by the appropriate choice of application route and gene transfer vector. This technique is highly adaptable to new developments in biology (for example, new signalling targets, new genetic regulators such as miRNA and improved light-emitting enzymes) and is applicable to any strain of mouse or rat. As proof-of concept several widely-used models of disease will be examined over the duration of this programme of work: i) LPS-induced lung inflammation ii) Bleomycin-induced lung fibrosis iii) LPS-induced liver inflammation iv) Carbon tetrachloride/ethanol-induced liver fibrosis v) collagen-induced arthritis vi) Cutaneous wound-healing following dorsal punch biopsy vii) Neonatal cerebral hypoxia/ischaemia

Field of science

  • /natural sciences/biological sciences/zoology/mammalogy
  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes
  • /engineering and technology/environmental biotechnology/biosensing

Call for proposal

ERC-2010-StG_20091118
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

UCL Elizabeth Garrett Anderson Institute for Women’s Health
Address
Gower Street
WC1E 6BT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 212 503,97
Principal investigator
Simon Nicholas Waddington (Dr.)
Administrative Contact
Greta Borg-Carbott (Ms.)

Beneficiaries (3)

UCL Elizabeth Garrett Anderson Institute for Women’s Health
United Kingdom
EU contribution
€ 1 212 503,97
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
Principal investigator
Simon Nicholas Waddington (Dr.)
Administrative Contact
Greta Borg-Carbott (Ms.)
QUEEN MARY UNIVERSITY OF LONDON

Participation ended

United Kingdom
EU contribution
€ 104 855,77
Address
327 Mile End Road
E1 4NS London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Gerard Collins (Mr.)
ST GEORGE'S HOSPITAL MEDICAL SCHOOL
United Kingdom
EU contribution
€ 153 912,26
Address
Cranmer Terrace
SW17 0RE London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Steff Hazlehurst (Ms.)