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Characterisation of eotaxin-induced recruitement of eosinophilic leukocytes and its application to the development of a gene therapy approach for asthma

Objective



Research objectives and content
The accumulation of eosinophilic leukocytes is a feature of inflammatory processes that characterizes allergic asthma. Recently eotaxin has been found to be a potent eosinophil chemoattractant whose transcription is upregulated in lung epithelial cells upon allergen challenge. The purpose of the research outlined in this proposal is to gain further understanding of the function of eotaxin and the interaction with its receptor. Dominant-negative forms of eotaxin as well as antibodies will be tested for their capacity to inhibit the eotaxin signalling and thereby to prevent eosinophil recruitment to the lung. A gene therapy approach seems to be very promising in this special case of a secreted protein requiring expression only at a relatively low level. Non-viral gene delivery will be used to express dominant negative mutants of eotaxin or single chain antibodies against eotaxin or its receptor in lung l epithelial cells of mice.
Training content (objective, benefit and expected impact)
While working with the eucaryotic model organism S. cerevisiae I gained thorough experience in a broad spectrum of techniques in molecular biology, biochemistry and cell biology. This knowledge I would now like to apply to mammalian systems and thereby contribute to the development of new therapeutic strategies.
Links with industry / industrial relevance (22)
The research will be carried out at the RPR research centre at Dagenham where well-established in vitro and in vivo models of asthma are available. Thus a quantitative evaluation of the potential therapeutic use of the proposed gene therapy approach will be possible.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

Rhone-Poulenc Rorer
Address
Rainham Road South
RM10 7XS Dagenham
United Kingdom