Marie Nugent - How Can a Fly Tell the Time?

Almost every living organism has an intrinsic time keeping mechanism in order to keep its physiology optimum to its environment, from the humble fruit fly to humans. In this article, Marie Nugent of the Department of Genetics describes her research exploring the workings of the circadian clock in fruit flies.

About My Research

Our environment is characterised by 24 hour cycles in light and temperature. These fluctuations let us know the time of day and help our body clock (circadian clock) adjust accordingly. In fruit flies, Drosophila melanogaster, light detection occurs via a blue light sensitive protein called CRYPTOCHROME (CRY). This allows the body clock of the fly to adjust so that its physiology and metabolism is optimum for its environment. This process is important for almost all living organisms, from humans to bacteria.

CRY has been shown to be involved in many physiological processes in flies; however my project focuses on how it changes the activity of clock neurons that are involved in controlling sleep and arousal in the fly brain. When nerve cells are active, they give off an electrical signal that can be recorded and analysed. Using this principle, electrical recordings of these cells can allow insights into what changes CRY is able to make to allow the body clock to change with its environment. To do this, a continuously active form of CRY called CRY∆ is used to amplify the effects of normal active CRY in clock neurons.

Not much is known about the electrical activity of clock cells in the adult fly brain. This project aims to characterise this, as well as determine the mechanism behind CRY’s ability to increase clock cell activity.

Research Approach

Fly Patch ClampThere are many genetic tools available to use in the fruit fly model in order to achieve specific expression of genes in particular types of tissues. For example, I have been able to specifically express CRY∆ in the motor neurons of the fruit fly larvae to assess if there is an effect on their crawling behaviour. 

I have also been able to express CRY∆ in the clock cells in the fruit fly brain to see if this changes their electrical activity. I am able to see if there are changes in the electrical activity in clock cells by using a technique called whole cell patch clamping. When nerve cells are active, they give off an electrical signal that we can record using this method. The technique involves using a small glass pipette filled with conducting solution and an electrode that can simultaneously give out current and record changes in the electrical activity of the cell. 

To do this the glass pipette has to adhere to the cell membrane and burst it open within the pipette so the conducting solution in the pipette and the cell cytoplasm are in contact.

Research Findings

The results so far indicate that CRY∆ is able to increase the activity of the neurons it is expressed. When expressed in the motor neurons of fly larvae, it causes them to crawl faster. When expressed in clock cell neurons, it causes them to be more active after being injected with current. 

We have also found that the clock cells we are interested in characterising are more diverse in their activity than previously thought. This could suggest that even within this small subset of clock cells, there is more diversity in their electrical activity than would be expected.

The aim is to continue to use CRY∆ to help dissect how CRY is able to elicit increases in electrical activity. We would also like to determine the factors behind the diversity seen in the clock cells and the function of this diversity.

Biologists have known for years that important physiological mechanisms are highly conserved throughout evolution.  If the humble fruit fly has even more complex mechanisms to help with its time-keeping than we first thought then there are implications that we do too. Most people are aware of their own ‘body clock’ and how this affects them day in, day out. There are also implications on how this influences the progression of human diseases, in particular heart disease which is still the biggest killer in the Western world.

About Marie Nugent

Marie NugentMarie Nugent is a research student working towards completion of her doctoral degree in the Department of Genetics. Marie holds a studentship from the Biotechnology and Biological Sciences Research Council.

Marie is supervised by Dr Joern Steinert, Professor Ian Forsythe, and Dr Ezio Rosato.

Department of Genetics
University of Leicester
Adrian Building
University Road

Marie will present her work at the Festival of Postgraduate Research 27 June 2013 - see Marie's Festival poster.

The Festival is open to all members of the University community and the public - book your place here.

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