NICOTINIC RECEPTORS · Viral vector and RNAi strategies to determine the role of beta2 containing nicotinic receptors in aversive learning
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-02-01 → 2008-01-31
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
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Results in brief
Final Activity Report Summary - NICOTINIC RECEPTORS (Viral vector and RNAi strategies to determine the role of beta2 containing nicotinic receptors in aversive learning)
Nicotine, the main addictive component in tobacco, acts at nicotinic acetylcholine receptors (nAChRs) present throughout the brain. Understanding the consequences of nAChR activation in the brain and its relationship to both addiction and other psychiatric disorders will be of great societal value. Investigating the underlying neuroscience provides information that will point to new targets for interventions and therapies that will reduce tobacco consumption or treat psychiatric disorders. This project has served to begin the development and validation of new tools to study nicotinic receptor function in vivo. Five shRNA constructs, tagged with green fluorescent protein (GFP) have been developed in viral vectors that we can use to down-regulate nAChR function in specific areas of mouse brain, the GFP acts as a marker so we can ascertain the site of infection and gene down-regulation in the brain. These constructs utilise a cutting edge technology where RNA molecules targeted to specific DNA sequences are able to interfere with gene expression and thus selectively down-regulate the gene of interest, in this case beta2 subunit containing nicotinic receptors. Future studies will use these constructs to study the role of nicotinic receptors in passive avoidance behaviour. A fear associated learning paradigm that is sensitive to both nicotine administration and disruption of nicotinic receptors (in beta2 knockout mice).
Data: CORDIS, © European Union
Project objective
Dr. Sarah King has recently returned (August 2004) to the UK after working for seven years in the Department of Psychiatry, Yale University, USA. As a new Lecturer in the Department of Psychology at the University of Sussex (permanent position) Dr. King endeavours to set up an active and internationally competitive research programme studying the actions of nicotine and role of nicotinic receptors (nAChRs) in brain function and psychiatric disorders. Dr. King requests funds to aid this reintegration back in to Sussex, the UK and Europe by supporting the costs of a technician, equipment and consumables. In the USA, Dr. King worked with transgenic mice, generating lines with temporal and region specific expression of beta2 subunit containing nAChRs, and tested hypotheses as to the brain circuitry underlying the role of nAChRs in behavioural processes. By bringing the expertise and knowledge gained in the USA back to the UK, Dr. King wants to further develop and use new genetic tools to study nAChR function in vivo.Combining the transgenic work with cutting edge techniques, viral-mediated gene transfer and RNA interference, will provide novel and efficient methods to study nAChR function. These tools will be used to determine the brain circuits in which nicotine acts to enhance aversive learning. This work falls into the objectives of the 6th Framework Programme. Dr. King is an ideal candidate for a Marie Curie Mobility Action International Reintegration Grant. Having returned to the UK from the USA, she can introduce these new and cutting edge techniques, and provide an invaluable contribution to the European research community, by advancing European research in the field through her essential knowledge, experience and position. Dr. King's research objectives and plan fit solidly into the Life Sciences, genomics and biotechnology for health research area, specifically on the research topic's studying the brain and combating diseases of the nervous system.
Original text from CORDIS.
Participants
- UNIVERSITY OF SUSSEX · BRIGHTONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union