Optical Imaging of Fly Brains for Neurodegeneration Research

Approximately 1 million people in the UK alone are suffering from neurodegenerative diseases, and the number is rising. They pose a huge burden on individuals suffering from these devastating diseases, their relatives, and the economy as a whole, and despite all research efforts there are currently no cures. A key phenomenon linking diseases such as Parkinsons and Alzheimers is that proteins, which are normally harmless, start to change shape, to aggregate and to misbehave so as to become toxic to the neurones in the patients brains. Nobody knows what mechanisms leads to this dysfunction nor how to prevent it. A huge problem is that one cannot with current tools follow how the proteins form into toxic structures in living individuals. What we propose here is to develop, by drawing on the expertise of physicists and geneticists, a novel platform that will permit us to study the formation of such toxic aggregates directly in living brains, not human brains of course, but the brains of fruit flies, which are amenable to optical microscopes and can serve as models of what might be going on in humans. If we succeed in building such a technology, we would have a tool with which to understand the disease and with which to test potential drugs which prevent the toxic structures from forming.

The aim of this proposal, submitted under the discipline hopping initiative, is for a geneticist to cross the boundary into optical engineering to develop technology with which it is possible to image the formation of toxic protein aggregates in living fly (Drosophila melanogaster) brains. We seek funds for Claire Michel from the department of Genetics to join the Laser Analytics group of Dr. Kaminski in the Department of Chemical Engineering, where novel optical microscopy platforms are being developed. Ms. Michel will be given thorough training in the design and operation of multimodal imaging technologies, co-ordinated through a combination of practical research in instrumentation design and data processing and workshops (which are to be funded and organised through the CamBRIDGESens network (http://sensors.cam.ac.uk), of which Kaminski is the director and which is funded by the EPSRC Bridging the Gaps initiative. We thus ask for Ms Michel, whose background is in Drosophila genetics, to be funded for 12 months to ?discipline hop? into an optical engineering lab. Simultaneous with this activity two other discipline hops will take place: Kaminski, the PI, is a physicist with no background in biology, and he has timed this project to coincide with a research sabbatical which he will use to learn about genetic manipulation of flies, dissection of fly brains, and fundamental aspects of neuronal disease research in fly models, practical aspects of which he will learn from Claire Michel. The fly genetics laboratory of Dr. Damian Crowther, where Michel performed her PhD work, will also benefit from the ?discipline hop?: By obtaining a fundamental understanding of the potential and limitation of modern imaging techniques it will be possible to guide future high impact experiments with which it will be possible to elucidate functional aspects of potential drugs directly in flies to serve as a flexible and high level model for neurodegenerative disease.