The AOX effect

You can see three tubes in the following video, each of which contains 10 flies – all alive. On the left (“controls”) , all flies comfortably climb upwards after being tapped down. These are unaffected flies. The ten flies in the middle (“COX def.”) , however, are too weak to climb, due to the lack a key protein in their nerve cells. The flies on the right (“COX def. + AOX”) also have the same deficiency, but they also have an additional protein called alternative oxidase (AOX) in the same cells, and now they can climb again (This experiment was previously published in the Scientific Reports journal).

Here is a quantification of the repeat experiment, also showing a dose-dependent effect. The y-axis, “Climbing index”, shows how well flies can climb. The controls can climb very comfortably, and AOX expression alone does not affect this. However flies with pan-neuronal cytochrome c oxidase (COX) deficiency are unable to climb without AOX. High levels of AOX expression in nerve cells dramatically rescues this phenotype. Lower levels of AOX in the same cells gives a milder (but statistically significant)  rescue. Finally, inactive AOX (inactived by mutations in its active center) does not help at all.

The effect of neuronal COX deficiency on locomotor abilities, and its rescue by AOX expression. Center lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles, data points are represented by dots. p<0.001, One-way ANOVA.

Using neuronal COX deficiency in Drosophila melanogaster as a disease model, I am studying how COX deficiency in neurons leads to locomotion problems. My focus is the type of neurons affected, and the pathological mechanisms by which they are affected. I also explore how AOX alleviates these phenotypes and processes.

Why the Fly?

Two weeks ago we organized a public outreach event in the Science Cafe of the University of Helsinki. Presenting were Essi Havula from Ville Hietakangas Lab, Martin Kracklauer from Osamu Shimmi Lab, and myself from Howy Jacobs Lab.

Each of us gave a 15-minute talk on why the hell scientists use fruit fly in their research and what results they got. Essi’s talk was in Finnish, followed by Martin’s and mine in English. Mine was about how neuroscientists made use of the fly.

A video of the talks is available online on the university website.

The talks were followed by an actual fly show! We had a microscope and wild-type flies with ourselves, and interested people from the audience did get a chance to see the flies.

We thank Toni Rönni from Think Corner for the opportunity and support.

Here are some instants from the event, courtesy of Selahattin Cin and Norman Zielke:

My Aivopesula talk on fly neurobiology

The scientist on the poster is Seymour Benzer, the father of Drosophila neurogenetics.
The scientist on the poster is Seymour Benzer, the father of Drosophila neurogenetics.

When I was a student in Kuopio, I was a member of the Aivopesula committee, made of volunteers arranging monthly neuroscience meetings. The main idea was not to just listen to a talk, but also to meet and discuss with other interested people in the university, the academic hospital and so on. At first coffee and cookies were served, followed by a not-so-long talk. The function of the meeting would be completed during the buffet with free snacks and beer.

It was great pleasure to do the shopping, prepare the snacks, chop the salads and prepare the buffet once a month with friends. And next week, I will have the privilege of giving the talk.

As far as I know, there is no Drosophila researcher in Kuopio, and I will try to convince the audience that Drosophila melanogaster is useful for neuroscience research, with some historical examples and some from our recent paper (Yalgin et al., 2015).

I will also touch upon our current work with alternative oxidase (AOX) in Howylab, Tampere.