Drosophila & Human Disease:
How the fly provides insight into brain disease & injury
Nancy Bonini
Lucille B. Williams Term Professor of Biology
I’ll start with DNA. We have been in the age of knowing the human genomic sequence since 2003 – that means we now know the entire DNA code of our genome – all our genes that make us who we are.
But still we have little understanding of how those genes and that sequence makes us who we are.
A continuing puzzle is to figure out how those genes work.
Primary among these fascinating challenges is the brain – the final frontier.
How do we make a brain? how does the brain work? what is a thought? how do we maintain our brain? how do we repair our brain in disease and injury?
This is where simple but extraordinary systems called “model organisms” take center stage. Model organisms like the fruit fly Drosophila. And where a technique – an old technique, a classic technique of scientists – called genetics – provides us the tool to unravel the puzzle of gene function in the brain. Via genetics, we generate mutant flies, lacking certain functional genes, and ask: what are the properties of this mutant fly?
The fly - the tiny fruit fly Drosophila - has the core set of genes that we have – the fly has our genome but condensed to a simple barebones form. The fundamental set of genes.
And it also has a brain – the fly has a brain much like our brain –organized into fundamental centers and units just like ours.
And it has brain function like ours: the fly can learn, can remember, it sleeps, it uses basically the same core set of genes to make its brain that we do.
Importantly, the genes function the same: so we can take a mutant fly that is missing a gene activity. Like a gene that makes the eye - without that gene, the fly is eyeless.
We can then take the human counterpart of that same fly gene – we can put that human gene into the fly, and that human gene will restore the eye to the fly.
That is human genes function the same in the fly as they do in us.
So with that, we can use the fly to tell us about the function of the counterpart human genes. And allows us to do it fast.
We can grow 100’s of flies within 2 weeks. We can see and examine in detail the brain with fast simple assays.
So this is what we are doing in our lab, we are using the fly to tell us about human brain disease and injury.
That is, we can take any human gene that causes brain disease and put it in the fly and re-create that disease in the fly – we can give the fly Alzheimer’s disease, Parkinson’s disease, Huntington’s disease. We can give the fly brain injuries like spinal cord injuries that cause paralysis.
so what good is it to give the fly such a disease?
Why, because we can then cure the fly– we use the power of fly genetics to screen for other genes that will delay or cure the disease in the fly.
And once we discover those genes, we can ask if those same genes and mechanisms function to delay or cure disease in vertebrates like the mouse model system, and then in humans.
Thus, using the simple fly Drosophila, we can merge knowledge of our genome – our DNA code – with simple approaches to brain disease and function – and find new ways to treat and cure them.
This approach is limited only by our brain – by our imagination our creativity in asking what interesting and important biological functions about the brain can we ask the fly reveal to us.
And most important - it’s fascinating & it’s fun.