Neuroscientist Michael Kunst discusses his work on fruit flies

By Guest

I was asked by your teacher Ms Baker to talk to you about my experiences of being a scientist. One of the biggest perks of being a scientist is that you can choose to work on something you are interested in. Also, it helps a lot that I can choose when I want to work. This can be a blessing and a curse. Yes, I can sleep in when I feel like it but that comes with the price of staying late, because at the end of the day, I still have to do my work.

A little bit about myself…I did my undergrad and graduate studies in Germany at the University of Göttingen. After I finished my PhD, I moved to New Haven, CT, to work as a researcher at Yale University. I myself am interested in brain networks that govern behavior. How they assemble, what do they look like and how they change behavior. I chose to work on the fruit fly Drosophila melanogaster, for the reason that they offer easy access to genetic manipulation, reproduce quickly, and most importantly, because the genes between human and flies are are similar. Just as an example, one of the most important genes regulating our sleep/wake cycles (the behavior the researchers in the Yale lab are working on), the gene period, was first discovered in a fly mutant. We and other labs all around the world are now using the genetic tools available for Drosophila to gain a better understanding of how genes shape this kind of behavior.

One of the most versatile tools we have in our arsenal is the GAL4/UAS-system (often referred to as the geneticists swiss army knife). With this system we are capable of expressing genes of interest in a defined subsets of cells (e.g. the nerve cells that are responsible for the daily rhythm of the fly). In this system we have two parts that regulate the expression of genes. One is the GAL4, which is a protein from yeast that activates transcription, but only of proteins found in yeast. What we do is to generate flies that have the gene for GAL4 in their genome. Then, we put a base pair sequence in front of the gene that would normally regulate the expression of a fly gene (this sequence is called a promoter), so that the GAL4 is now only expressed in the same cells that would also express the fly gene. Next, we generate a fly that has a copy of the gene for GFP in its genome. In front of this gene we put a UAS-sequence, this stands for Upstream-Activation-Sequence. The UAS-sequence is important because the GAL4-protein can bind to it and activate transcription of the GFP. If we now cross the two flies with each other the offspring will produce the GFP protein only in the cells in which the GAL4 protein is expressed. On the picture below you can see an illustration of how this technique works and an example that shows a fly brain in which GFP is expressed in very specific brain cells that are responsible for daily rhythms.

Why do you think it is better to have a two parted system for gene expression then just putting the GFP under the control of the promoter?

Over the last two decades laboratories all over the world generated thousands of fly strains that express GAL4 in different tissues and also thousands of flies that have different genes under the control of the UAS-sequence. From this, various genes and networks can be discovered that are important for such behaviors as sleep, learning, and decision making.

  • Bjoe

    To begin, Thank you so much for sharing your personal experiences with us, Dr. Kunst. Everything was very interesting, especially to get a very close look at a scientists life, interests, and work.
    This blog post focuses in on a more in depth and specific example of experimenting with fruit flies, chosen because of the extremely similar genetic build with humans. Dr. Kunst proceeds to explicate the process of using a tool called the GAL4/UAS- System, which is also known as the geneticists swiss army knife- which i found to be quite humorous. Essentially what this system does is it provides scientists with the ability to express genes of interest in a particular cell (s). This system provides you with two parts to regulate expression in the genes. One of which is the GAL4, a protein in yeast that activates transcription. The next process is to put a base pair sequence in front of the gene that would usually regulate the gene. Now, the GAL4 gene is expressed in the cells that would express the fly gene. Next, Dr. Kunst described that we would have then generated a fly with a gene for GFP in its genome. Then, in front of that, it would be necessary to put a UAS- sequence – standing for Upstream Activation Sequence. The importance of this step is that the GAL4 protein can then bind to it and cause transcription of the GFP. Now, if one breeds two flies together, the off spring will produce that same GFP protein only in the cells which GAL4 is expressed.
    And my thoughts on the question posed, I think it is better to have a two parted system for gene expression because it helps regulate it even more. I feel that the fact that it is broken into a specific system, it would cover any chances of faltering.

  • Bridget O’Hara

    This article was very interesting to read because it gave me perspective on how biologists do research in a lab. It is easy to think of a fruit fly as a very simple organism and not recognize their biological significance. Despite what many may believe, these flies have enough in common with humans for scientists to perform tests on them that simulate things that occur in the human genome. The GAL4/UAS-system described in this article that allows for scientists to regulate the expression of genes in fruit flies is useful. With GAL4, which is a protein from yeast activating transcription, gene expression is controlled for the proteins found in yeast. Flies that have this gene are generated by scientists and then a base-pair sequence is placed in front of a promoter (area that normally regulates expression of a fly gene). This causes GAL4 to be only expressed in cells that also express the specific fly gene. Afterwords, a fly with the GFP gene is generated. A UAS-sequence goes in front of this gene, making it possible for the GAL4-protein to bind to it and cause transcription of GFP. When the flies are crossed, the new generation will have GFP expressed in cells where the GAL4 protein is present. This two part system for gene expression is amazing because it allows scientists to manipulate genes in order to see expression in offspring. When the two traits come together, the desired trait is shown in the next generation. This article, which highlights gene expression in fruit flies, made it clearer to me how important studying other organisms is to humans. For example, by observing flies that posses the shaker gene, it helps scientists or even students understand the effects of episodic ataxia in humans.

  • Natalie

    Thank you Dr. Kunst for taking your time and writing this blog post which helps us learn a little more about what it is like to be a scientist in your field of expertise. GAL4 is a protein from yeast which activates transcription from other proteins that are found in yeast. To begin the GAL4/UAS-system, in order to express genes of interest, it is necessary to have two flies, one with GAL4 in its genome and one with GFP in its genome. Scientists take the fly with the GAL4 and then put a promoter in front of some gene that regulates gene expression. Now, GAL4 is expressed in the same cells that also express that gene the promoter was put in front of. The other fly, with the GFP in its genome, is then taken and a UAS sequence (Upstream Activation Sequence) is put in front of the GFP so that GAL4 can bind to it and start transcription. The two flies are then bred and the offspring produced have GFP in the cells where GAL4 is expressed. As for Dr. Kunst’s question, I’m honestly not sure, but I think it is easier to have a two parted system for gene expression because it ensures that the gene will be expressed and that it will be passed down to offspring. If only one parent has a gene that is changed, there is no guarantee that the offspring will also have that change. Since we just did a case study with fruit flies which had the shaker gene, it was nice to be able to read about the work that you do with fruit flies, so thank you again.

  • Ammar

    Dr. Kunst summarizes the GAL4/UAS-system and how it is essential in controlling the expression of genes of interest in a defined subset of cells. This system is broken into two parts: GAL4, which is a protein used to activate transcription, and UAS, or Upstream Activation Sequence, which needs to bind to the GAL4 in order to allow it to activate transcription. So, this essentially means that both parts of the system must be present in order for transcription of the specific protein to take place. Dr. Kunst specifically mentions GFP, or Green Fluorescent Protein. As the name suggests, this protein makes the fly glow green. Now, by taking a fly which has a copy of the gene for GFP and placing the UAS in front of it and crossing it with a fly that has the gene for GAL4 in its genome, we may obtain flies that express the GFP wherever it may have been placed. In his blog post, Dr. Kunst specifically mentions GFP in the brain cells.

  • Pauguste

    The article shows the usefulness of fruit flies. Since fruit flies have well of 90% of the same genetic make up as human being, they are ideal lab subjects. Fruit Flies reproduce rapidly and are susceptible to mutations with each generation of flies. We then can insert the GAL 4 gene in specific fruit fly ths expressing the fly gene in the future offspring. Then the GFP gene is inserted in front of the UAS sequence. This causes the synthesis of the GAL4 in transcription. Finally the two different type of flies are mated with each other so their offspring have the GAL4/GFP sequence. The picture then shows the daily patterns of the fly within its brain.

  • Bchristian

    Drosophila melanogaster fruit flies are an ideal test subject for efficiently experimenting with genetics related to humans. These flies show large similarities with human genes and are also an efficient way to test and regulate particular genes because they reproduce quickly. These flies are used to see how certain genes affect human and fly behavior. The GAL4/UAS-system allows one to express a desired gene in cells. The system uses proteins called GAL4 , that activates transcription in yeast. Scientists are able to produce flies with this gene and place a promoter in front of the gene that is normally used to generate fly genes. With this technique, GAL4 is expressed in the cells that code for the fly gene. A fly with the GFP gene is generated with a UAS-sequence preceding it. With this sequence, the GAL-4 protein can bind to it and activate transcription of the GFP. When the two flies cross each other, their offspring produce GFP proteins in cells that the GAL$ protein is expressed.

  • Pdrogaris

    With the GAL4/UAS-system scientist and researchers have the ability to select certain cells and express a certain gene within those cells. The example being used was the nerve cells responsible for the daily rhythm of the fly. There are two parts to this system/process. The first part involves a certain protein called GAL4 which is found in yeast cells and activates transcription. Scientist make flies with the gene GAL4 in their genome. They then put a promoter sequence in front of the gene that controls expression of the fly gene. So the GAL4 (protein that activates transcription) is now only expressed in the same cells that would also express the fly gene. That’s what a promoter does. Next flies are made with a certain gene in their genome (GFP). If front of this gene we put the UAS (upstream activation sequence) sequence. The GAL4-protein can bind to the UAS site and activate transcription of the GPF gene. Basically the GAL4 a protein that can activate transcription is capable of binding to UAS- sequences, so putting a UAS in front of a gene you would like to copy and express is possible given that you have the gene for GAL4. Putting the GAL4 on specific cells controls this

  • Josh b

    Josh Bence, great post, in 2009 i read an article on fruit flies that talks about research that may help autistic children react and study better in school. Linda L. Restifo of the Arizona Research Laboratory at The University of Arizona uses drug screens on fruit fly brains that may help develop a medicine that could combat the symptoms of mental retardation or autism. These drugs have already been approved by the U.S. Food and Drug Administration to determine whether and how well those drugs can change the size or shape of genetically abnormal brain neurons. If this is true and works there might be a way to cure autism but there is no promise but the drugs could find a way to tone down these symptoms and actually help autism kids. Unlike Sarah Palin said this research is helping kids with disabilities.

  • Anonymous

    Wow Josh, great comment i looked further more into the Fruit Flies linking to autism and i found a great website saying how the neuron and nerve cells in a fruit fly brain can link to advances in medecine to help control or even prevent Autism. Scientists claim that this has definatley boosted research for autism, but may lead to some great historical studies. Scientists say it has to do with the amount of protein in the person’s body when born. The article states
    “Currently, Bhat and other scientists are working to identify the proteins that neurexin binds to, how they interact, and what sequence of events ultimately results in the organization of synapses within nerve cells. The hope is that such studies in Drosophila will one day clarify the role neurexin plays in learning and memory, ultimately leading to a better understanding of how defects in this protein can lead to human disorders such as autism, Bhat said.” You can read this great article at the bottom of the comment.

  • Anonymous

    Great Post! I was interested when Dr. Kunst mentioned how the sleep habbits between humans and fruit flies are similar, and I was also interested becauase I have never hear dof this species of fruit flies. In our biology class there are a lot of fruit flies in our room. In the beggining of this year we had done a lab on fruit flies. I foudn fruit flies interesting so I figured I would comment on this interview. Drosophila is a species of Diptera, or the order of flies, in the family Drosophilidae. Scientist sometimes refer to it as the vineager fly. When a Drosophila is developing it varies do to temeprature. Female Drosophilas are very fascinating. They becomeable to mait with males at about 8–12 hours after emergence. For humans it takes us a decade if not less depending on when you reach the phase of puperty. Fruti flies are also used to study autism. Other studies performed an experiment on fruit flies that experimented with the limits of natural selection.

blog comments powered by Disqus

Recent Comments

Powered by Disqus

Extreme Videos


February 2011
« Jan   Mar »
  1 2 3 4 5 6
7 8 9 10 11 12 13
14 15 16 17 18 19 20
21 22 23 24 25 26 27

Search Extreme Biology