An open LSTM Seminar from guest lecturer
Prof David B Sattelle
UCL Respiratory, Division of Medicine, Rayne Building, University College London WC1E 6JF
Introduced by Dr Gareth Lycett
About the Seminar
The short pipeline of new chemicals for the control of soil-transmitted helminths and the insect vectors of major tropical diseases such as malaria, together with the pressing problems of resistance point to an urgent need to develop high-throughput assays in the search for new compounds and in the quest for ways to extend the life of existing chemicals. We have developed methods for rapid, automated measurement and analysis of nematode and insect motility using a 96-well plate based platform, high-speed filming and the use of algorithms.
In collaboration with colleagues at the Universities of Manchester and Oxford we have used this technology to undertake library-scale chemical screens. By this means we have identified novel hit compounds that immobilise adult Trichuris muris and may have potential for meeting the unmet need for the control of trichuriasis, caused by the whipworm Trichuris trichuria, which affects 500,000 people. No adverse effects were seen in cell-based toxicity tests and although a selected hit did not affect embryonation, pre-treatment of eggs prior to infection reduced the host’s parasite load, illustrating the potential of this type of chemistry for use as a spray to prevent re-infection as well as an oral anthelmintic.
Using a separate set of algorithms we found that we can quantify aspects of the motility of larvae of the mosquito Anopheles gambiae, a vector of malaria. We measure both overall larval motility and the probability of larval “jumping”, the latter being a feature we can easily relate directly to an important component of larval behaviour. In collaboration with colleagues at The Liverpool School of Tropical Medicine, we are using this assay to measure dose- and time-dependent actions of insecticides and have shown our assay to be sufficiently robust to permit detection of resistance to deltamethrin, a pyrethroid insecticide. We are als exploring possible intrinsic behavioural differences between susceptible and resistant larvae and the prospects of an Iphone-based field assay for resistance.