Ode to the fruit fly research! – Drosophila rule!! – Marco Gallio – @US_Conversation

Ode to the fruit fly: tiny lab subject crucial to basic research

Marco Gallio, Northwestern University

The world around us is full of amazing creatures. My favorite is an animal the size of a pinhead, that can fly and land on the ceiling, that stages an elaborate (if not beautiful) courtship ritual, that can learn and remember… I am talking about the humble fruit fly, Drosophila melanogaster. By day, a tiny bug content to live on our food scraps. By night, the superhero that contributes to saving millions of human lives as one of the key model systems of modern biomedical research.

Fruit flies entered the laboratory almost through the back window a little more than 100 years ago. The excitement was still fresh after rediscovery of Gregor Mendel’s work on the genetics of peas in 1900. It was an outlandish notion at the time that Mendel’s simple laws of inheritance could apply even to animals. To test this revolutionary idea, scientists were looking for an animal they could keep easily in the lab and reproduce in large numbers.

Thomas Hunt Morgan struck gold when he decided to use the fruit fly as a model. He and his students pushed this prolific little animal to great success. They furthered Mendel’s work to discover that genes are located on chromosomes, where they are arranged, in Morgan’s words, like “beads on a string” – a breakthrough that was recognized with the Nobel prize in 1933. With the success of Morgan’s “flyroom,” the humble fruit fly was set on its way to becoming one of the leading models in modern biology, contributing vast amounts of knowledge to many areas – including genetics, embryology, cell biology, neuroscience. Additional fly Nobel prizes were awarded in 1946, 1995, 2006 and 2011.

A tiny fly stands in for us in basic research

If you ask a geneticist, humans are brothers to mice and just first cousins to flies, sharing 99% and 60% of protein-coding genes, respectively. Our anatomy and physiology are also related, so that we can use these laboratory animals to design powerful experiments, hoping what we find will be of significance to animals and humans alike. It’s undeniable that the research on animal models – such as nematodes, flies, fish and mice – has contributed immensely to what we know about our own body and as a result is helping us tackle the diseases that plague us. On this front, the services of the fruit fly will certainly be required for some time to come.

Studying fly brains to understand our own

A recent renaissance in neuroscience is also bringing the fly to the forefront of our efforts to understand the brain. One of the things we least understand is how our own brain produces our emotions and behavior. Scientists are naturally attracted by the unknown, making this one of the most exciting open frontiers in biology. Perhaps, our brain, the ultimate Narcissus, cannot resist the temptation to study itself. Can the humble fly really contribute to our understanding of how our own brain works?

The fruit fly brain is a miracle of miniaturization. It deals with an incredible flow of sensory information: an obstacle approaching, the enticing smell of overripe banana, a hot windowsill to stay away from, a sexy potential mate. And it does this literally on-the-fly, as the little marvel is computing suitable trajectories around the room. Yet the fly brain is composed of only about 100,000 neurons (compared with nearly 100 billion for human beings) and can fit easily through the eye of the finest needle.

The fruit fly brain, tiny compared to the mouse and minuscule compared to the human – but still so useful in research.
Dr Frank Hirth, King’s College London

The relatively small number of cells is a key advantage for brain mapping, and large efforts are under way to label, trace and catalog every single neuron in the fly brain. Combine this with the unique wealth of information on the genetics of this little animal, and you will see how we are now able to design incredibly powerful experiments in which we alter the “software” (that is, introduce specific changes in the genome) to create animals with unique and predictable changes in the “hardware” (the brain circuits) to ask questions about brain function.

Following this playbook are recent experiments demonstrating, for example:

 

Of course, we can do these kinds of experiments in a number of animal models. But the unique advantage of the fly is that we can pinpoint every single neuron that’s important for a particular response or behavior, precisely map how they connect to each other and silence or activate each one to figure out how the whole thing works.

Don’t forget the flies

Just a few weeks back, Chicago hosted the Genetics Society of America’s annual “fly meeting,” bringing together thousands of fly scientists from around the world. One of the topics discussed was that, in this tough economic climate, funding cuts to public agencies are disproportionately hurting research on fruit flies in favor of more “translational” approaches – that is, research that has more immediate practical applications.

It’s worth remembering that neither Mendel nor Morgan expected that their work could have a direct impact on medicine. Yet when, hopefully soon, we manage to “cure” cancer – a genetic disease par excellence – they should be among the very first people receiving a thank you note from humanity.

Flies still have a lot to contribute to our understanding of all aspects of biology. As with much basic research, the direct benefits from this work may be around the corner, or may take a little longer to find. It would be a big mistake to curb fruit fly research now that the flies are just getting warmed up to tackle some of the most interesting questions in biology.

The Conversation

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Fruit flies help researchers study human diseases. Mohit Jolly explains @ConversationUK

If you took #IceBucketChallenge you need to read about these fruit flies

By Mohit Kumar Jolly, Rice University

If you have a Facebook account, you are likely to have seen someone pour an ice bucket on themselves in the name of raising awareness for amyotropic lateral sclerosis (ALS). ALS is a disease that affects nerve cells in the brain, and it falls into a class of diseases known as neurodegenerative, which include diseases such as Parkinson’s, Alzheimer’s and Huntington’s. All of them are incurable and claim many lives around the world. These diseases can be caused by genetic mutations, but our understanding of what causes these remains poor.

A study, conducted by Manish Jaiswal and colleagues and led by Hugo Bellen and Michael Wangler at the Baylor College of Medicine, just published in Cell, takes a key step forward. They identified hundreds of new mutations in specific genes that are associated with various aspects of the development, function and maintenance of neural system in the fruit fly Drosophila melanogaster. The fruit fly is a stand-in for humans, and allows investigation of the molecular mechanisms of 26 human diseases, including ALS.

Researchers could use Drosophila melanogaster, because it is a well-established model organism to understand the molecular mechanisms of many human diseases. This is because: about 75% of human disease-causing genes are found in the fly in a similar form, it is easy to work with and breeds quickly, and many tools are available to manipulate any genes in it.

Messing with a fruit fly

The standard way of learning about genes is by studying the effect on the fly when a specific gene is “knocked out” from its genome. However, this strategy is sometimes ineffective – for instance, if the gene knocked out is an essential gene required for growth and development, then the fly will not fully grow, rendering the effort useless.

The authors overcame this limitation by inducing mutations in just a few cells in the fly, so that even if an essential gene is mutated, it does not kill the fly during its embryo-to-adult development. The effect of that mutation can be studied by looking at the tissue or organ where that mutation was supposed to act.

This is an important method because it helps to do experiments that can’t be done in humans. For instance, looking at the full genetic data of two siblings suffering from microcephaly – a disease in which size of the head is much smaller than expected – the researchers found that a specific gene, called ANKLE2, was mutated in both. This could be coincidence. But given there are 20,000 genes in the human genome, the chance of such a coincidence are quite low. To find out whether ANKLE2 is causing microcephaly, the researchers would need to conduct gene manipulation experiments in humans. Such experiments, however, are unethical.

Genetic shortcut

That’s when studying fly and human genetics together becomes crucial. The authors found that flies with mutations in the same gene had small brains too. However, when the human ANKLE2 gene was introduced in these mutant flies, they had a normal brain size, providing evidence from the fly that ANKLE2 is the culprit.

This technique allowed the authors to isolate 614 new mutations in 165 genes that affect the development, function and maintenance of a functional neural system. But what is perhaps more important is that, these results have helped the authors to suggest a new method for identifying various disease-causing human genes by looking at the mutations in the genomes of patients alongside the mutations in corresponding Drosophila genes. They find that the disease-causing genes in humans have more than one copy of them in the fly, so if one can enlist which genes have more than one copy in the fly, they are likely to be disease-causing in humans.

As more people use this method, we will get closer and closer to finally understanding the genetic basis of many neurological and neurodegenerative diseases.

The Conversation

Mohit Kumar Jolly does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations.

This article was originally published on The Conversation.
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#Science Quotable: Mark Gerstein on genetic model organisms!

encode

“One way to describe and understand the human genome is through comparative genomics and studying model organisms. The special thing about the worm and fly is that they are very distant from humans evolutionarily, so finding something conserved across all three – human, fly and worm – tells us it is a very ancient, fundamental process.” – Mark Gerstein on genetic model organisms, and the modENCODE and ENCODE projects.

Read more at: http://phys.org/news/2014-08-scientists-human-worm-genomes-biology.html#jCp

Spineless National Zoo has closed its Invertebrate Exhibit

worm

The Invertebrate Exhibit at the National Zoo is no more (so sad, this was one of my favorite exhibits at the zoo). This Sunday the exhibit closed its doors according to an article in NPR by Bill Chappelle.

The zoo says its exhibit of cuttlefish, butterflies, spiders, and other spineless animals, which first opened in 1987, needs $5 million in upgrades, along with $1 million annually. But officials say their fundraising priorities lie elsewhere, including a renovation of the zoo’s Bird House.

The exhibit of spineless animals “is not included in the zoo’s five-year strategic plan or its 20-year master plan,” the AP said Monday. “Plans call for a future Hall of Biodiversity, including invertebrates.”

Invertebrates lack a spinal cord and make up ~97 percent of all animals. Common invertebrates include worms, insects, clams, crabs (crustaceans), octopuses, cuttle fish, starfish, and snails.

Two of the most popular and important genetic model organisms are invertebrates, the fruit fly (Drosophila melanogaster) and the nematode (Caenorhabditis elegans). The use of these animal models by biomedical researchers has lead to huge discoveries in many biomedical research fields, including neuroscience, genetics, and biochemistry. These models have also been extensively used to study the genetics and molecular mechanisms underlying many human diseases. Both of these animal models have also been involved in research that led to scientists winning the Nobel Prize.