26 October, 2008

Sunday Sensational Science

Flies like us.

We had a pet fly for a few weeks one summer in Page, AZ. Friendly little bugger - he liked to hang out with us in the kitchen, never caused trouble, and would sit contentedly on a knee cleaning himself while we chatted. We felt a kinship with him.

Turns out there may be good reason for that.

Meet Drosophila melanogaster, the fruit fly. Yes, the same fruit fly Sarah Palin disparged just a bit ago. She mightn't be putting dear old Dro down if she knew how much we share. 61% of disease genes, in fact. 50% of mammalian genes, even so. Fruit flies have led to some - forgive me - fruitful research when it comes to understanding how genes affect everything from birth defects to why alcohol leads to lust.

They have a lot to tell us about how genes affect embryonic development, and about the diseases that result when our genes turn against us. They make effective research subjects for a variety of reasons. For one, they're not cute, so it's unlikely PETA's going to show up demanding we set them free. Secondly, their genes are elegantly simple, which makes them much easier to research and manipulate. Thirdly, their short life spans and profligate procreation means we can study them over generations in a usefully short amount of time. And finally, the fact we all evolved from the same source means we can apply what we've learned from them to other research animals, and eventually to us.

It starts with Hox genes. Those are the subgroup of homeobox genes that come in clusters on vertebrates, and basically let the developing embryo know what bits are where. They can get a little complicated in mammals, but they're dead easy in fruit flies:

I filched that illustration from PZ, who 'splains a lot better than I can sum up. All we need to know for today's purposes is this: Hox genes - fruit flies has gots 'em, and so do we.

This becomes critically important when we try to understand how genes make the mammal. Studying Drosophila gives us a basic outline of the processes involved. Once we've got those basics down, we can start translate that understanding to more complex critters. Like us.

Understanding the basics of how genes work is vital to understanding what happens when they don't work. Take birth defects. A lot of medications cause them, and mitigating those side effects is a huge thing. Imagine if we could understand how and why the medication is affecting genes, and come up with either alternative therapies or develop "rescue" therapies that will prevent the problem. Enter the humble fruit fly, who is now helping scientists do just that with MTX, a drug that treats everything from cancer to arthritis - but at a horrible cost. The flies suffer the same defects. Through them, we've discovered something important: "Many of the genes found to be affected by MTX are involved in cell cycle regulation, signal transduction, transport, defense response, transcription, or various aspects of metabolism."

Knowing is half the battle. And the humble little flies will allow us to test therapies as they're developed, eventually leading to fewer birth defects due to life-saving and life-enhancing drugs.

Need a bigger brain? Studies with Drosophila lately identified "timer" genes that regulate when and how stem cells stop producing more neurons. I'll let Dr. Alex Gould, who led the research, explain the importance:

Dr Gould said: "This discovery has relevance for future stem-cell based therapies in two ways. Firstly, while we know how to grow massive quantities of neurons from neural stem cells in a petri-dish, it’s also important to understand how to stop them growing if they are to be transplanted safely into a human brain."

"Secondly, we know that the human brain retains a few neural stem cells into adulthood. If we could learn how to influence the internal clock of these cells it might be possible to rejuvenate them so they can make replacement neurons. These could then be used to help repair damage caused by neurodegenerative conditions like Alzheimer’s or Parkinson’s disease.

That's tremendous. This research could end up helping us regrow damaged areas of the brain. It could end the tyranny of neurodegenerative diseases and brain injury. (And, as an SF author, let me just say it's fun to extrapolate this into the idea of a strap-on brain - who wouldn't want to grow an extra one to help us remember and comprehend things?)

From growing new brains, it's just a short hop over to understanding why some of them grow wonky. Take autism, for instance. We've got pretty good evidence that abnormalities in the gene neurexin 1 has something to do with autism. Neurexin is a critical protein - it's the stuff required for connections between neurons to form and function the way they should. How do we know that? Drosophila told us. And now it's going to tell us even more:

The discovery, made in Drosophila fruit flies may lead to advances in understanding autism spectrum disorders, as recently, human neurexins have been identified as a genetic risk factor for autism. “This finding now gives us the opportunity to see what job neurexin performs within the cell, so that we can gain a better insight into what can go wrong in the nervous system when neurexin function is lost,” said Dr. Manzoor Bhat, associate professor of cell and molecular physiology in the UNC School of Medicine and senior author of the study. The study, published online Sept. 6, 2007, in the journal Neuron, is the first to successfully demonstrate in a Drosophila model the consequences that mutating this important protein may have on synapses.
Pretty incredible stuff. Drosophila turns out to be quite the font of information - and it can tell us about ourselves even when it doesn't share our heart. Heartless (well, multi-chambered heartless) Dro has taught us quite a bit about the genes that play a role in the development of one of our most vital organs. It's also got plenty to teach on the subject of diabetes. While fruit flies don't suffer from that disease, they share almost all of our insulin-signalling circuits. That wonderful fact has already, in just two short years, led to three new drug targets.

Amazing that an insect, a pest no less, shares enough in common with us to help us understand how our biology works and how to fix it when things go awry. Drosophila, it turns out, may be among our best friends. Move over, Rover.

Just be careful if you buy Dro a drink to celebrate our commonalities. They, ah, lose their inhibitions and, well, might get a little fresh. Among other things.

See here for an eye-popping list of Drosophila research. As always, click the pics for sources and additional delights.

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