Large NHMRC grant supports study of genes that affect appetite in flies, mice and humans
02 November 2011
Neuroscientists at Garvan have been awarded a $1,840,000 five-year project grant from Australia’s main medical research funding body, the National Health and Medical Research Council. Ranked within the top 3 out of 3,500 project applications, the study will screen the whole genome of the fruit fly, looking for genes that affect appetite and energy expenditure, which are also ‘conserved’ across species. The genes identified will then be examined for their effects in mice and people.
The project combines the knowledge and experience of Professor Herbert Herzog and Dr Greg Neely. Herzog is a world-renowned expert in appetite with a strong track record using mouse models. Neely is an expert in using comparative genomics approaches to dissect the conserved genetics of instinctual behavior.
“We are actually using a very simple paradigm to identify new genes in the appetite and obesity area,” said Herzog.
“We know that there are significant differences in the ways that animals of the same species use food, depending on their genetic make-up. They can eat exactly the same, but one gains weight and has more fat, whereas the other one stays exactly the same weight. So there must be mechanisms behind energy partitioning in the body that we do not yet understand.”
“With the fruit fly, we can measure food intake fairly simply by feeding them coloured food for a particular period of time – blue food as it happens.”
“Fruit flies are translucent, and so the amount of blue in their bodies is easy to measure.”
“We can also put them through various metabolic tests, as well as measuring body fat and triglycerides.”
“Once Greg’s lab has identified a handful of promising genes, my lab can assess the function of those genes in mice.”
“Obviously the most interesting genes will be those whose function we still don’t know. That proportion is still quite high – around 45 % of all genes.”
Greg Neely recently identified all the genes in fruit flies that are required for them to perceive pain. He will be approaching this project in exactly the same way, using gene libraries and bioinformatics tools, in conjunction with laboratory experiments.
“Fruit flies get hungry and eat, and so do we. That’s regulated through the nervous system and through genetics, and will likely be conserved from the fruit fly to us” he said.
“Basically we look at the whole genome – every gene that’s conserved between us and fruit flies – and take each one out, one by one.”
The first phase of the project will involve measuring the food intake and metabolism of 8,000 different strains of fly – around 60 flies at a time.
The second phase will be knocking out the most promising genes in mice, and carrying out similar measurements.