Dr Cahir O'Kane works at the Department of Genetics at the University of Cambridge.
Dr O'Kane's talk was around the study of HSP in Drosophila - also known as fruit flies. The first aspect was why do we do this. Firstly, they have a short development period, going from egg to adult in around 10 days. Also they are small, so one wall of the room at Cambridge can hold 15,000 flies. They have 4 of these rooms and there are several groups working with these flies.
Flies and humans had a common ancestor with humans around 600 million years ago, which means that flies share about 80% of their genes with us, including the HSP genes. The team are able to breed paraplegic larvae, and as they age they lose the ability to climb. You can see this here: http://labs.cellbio.duke.edu/kinesin/WTKHClarvae.html.
These flies have axons in a similar way to humans. Nerve fibres or axons are typically up to 10,000 times longer than a cell body, and cell engineering is needed to maintain the axons. In HSP the longer axons breakdown first.
We have around 20,000 genes and the fly has around 14,000. Over 70 HSP genes have been cloned, and more continue to be found, around one every couple of months. Each gene disrupts a particular protein. Figure 2 here http://sp-foundation.org/file_download/510e252f-c9ec-484c-a90b-8f95372a499f shows which HSP genes affect which parts of the nerve fibre. Within this figure tubular endoplasmic reticulum (ER) can be seen, which forms a network within the cell. The axons in the fly have a similar ER shape.
Some of the HSP proteins have roles in the integrity of axonal ER in any organism. The research on the flies shows that if a fly is bred with the removal of one of the SPG/HSP genes there are mild effects, and with the removal of multiple HSP genes the ER becomes fragmented - and the nerve no longer functions as intended.
What does the future hold? It is possible that the functions of axonal ER could be altered by drugs, however at the moment it is not known which of these are important to maintain the axon.
The researchers have shown that it is possible to genetically reverse HSP in flies, but they are some way off being able to do this in humans in the embryo. The two of the issues putting this into practve are that there is a much larger risk of miscarriage, and that this is prevented by biomedical regulations (ethics). The researchers dont know all about neurons yet - if the letters in the DNA were printed in a book the human genome would take around 2000 books to print it all. Each gene within the DNA is several thousands of letters in length.
Dr O'Kane mentioned the Tom Wahlig Foundation (http://www.hsp-info.de/en.htm) who research HSP and promote an international network of HSP researchers.
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