Molecular determinants of ageing – quantitative response of fruitflies to adult-specific RNA interference (RNAi)

In order to improve our understanding of molecular mechanisms of ageing we will examine ageing processes in the fruitfly Drosophila melanogaster. To this end genes will be identified that increase life expectancy; and their effects will be studied in adults as these age. Besides exploiting modern molecularbiological methods that allow the individual inhibition of particular genes specifically in adult flies, behavioural studies of ageing will also be performed.

Mathematical models allow a joint analysis with genome-scale measurements of molecular effects. Besides contributing to an optimized experimental design, bioinformatical methods will be used to detect causal relationships between individual genes and ageing processes.

Project description

We investigate molecular mechanisms of ageing in complex multicellular organisms by adult-specific gene silencing in fruitflies (Drosophila melanogaster). Triggering temperature sensitive RNAi only in adult life allows, for the first time, the complete separation of developmental effects in a screen for longevity. In addition, multi-dimensional phenotypic and behavioural assays over the entire adult life of the flies permit a focus on lines that live long and well. Molecular effects of candidate genes on ageing will be thoroughly studied over time and genome-wide using RT-PCR and microarray time-courses. Integrated analysis of molecular, phenotypic, and behavioural data requires the development of modern probabilistic methods at all stages of the project, providing 1) optimal experimental design, 2) identification of causal consequences of target gene silencing, and 3) sensitive detection of molecular processes differentially affected during ageing.

Partners

We collaborate with Dr. Barry Dickson and Dr. Nadege Minois of the Research Institute of Molecular Pathology (IMP). All fruitfly work is performed at IMP while quantitative molecular measurements and computational analyses are conducted by our group at Boku.

Funding

Support for this project was won through competition in the WWTF Life Sciences Call 2005.