Sleep and learning: a genetic approach. The allnighter gene.

Background

Sleep is a vital activity, whose function still remain mysterious despite centuries of scientific research. All animals that have been tested so far, from nematodes to humans, possess and require the fundamental characteristics of sleep. In Drosophila, like in humans, sleep deprivation leads to a remarkable decrease in intellectual performance, learning and memory; chronic sleep restrictions also shows widespread metabolic changes and eventually leads to unexplained death.

My laboratory investigates the many functions of sleep using mainly the fruit fly Drosophila melanogaster as model organism. In particular, current research is aimed at elucidating the connections between sleep and synaptic plasticity, learning and neuronal homoeostasis. In previous work we provided evidence of how sleep may function as a mechanism to maintain a proper homoeostasis for synaptic strength and connections in Drosophila (see [1] for a recent review). We are now extending that line of work and we employ a rich selection of multidisciplinary techniques ranging from genetic manipulation of Drosophila (with transgenes and RNAi) to computer assisted analysis of behaviour to measure intellectual performance, including odours recognition and ability to court and mate.

The project

Following a genome wide screening for short sleeping mutant flies, we identified a novel gene that we called allnighter. allnighter mutant flies are viable but sleep considerably less than wild type controls and show general symptoms (such as tense “eagle” wings) that strongly suggest an underlying problem with neuronal excitability. 

The project aims at extending the characterization of this gene, and other belonging to the same family. Some of the questions that you will try to answer are: “where is the gene express and at what stages of development? Does expression change with sleep or experience? Is the enzymatic activity of allnighter required for its function? How do allnighter flies perform when challenged with task measuring their learning and memory capabilities”

Techniques. Working with Drosophila

An MRes rotation in Drosophila allows the unique opportunity to investigate a biological problem in vivo and yet follow the development of a relatively complicated project from the beginning (e.g.:genetic manipulation of a new animal) to the end (e.g.: behavioural testing of the new phenotype). Your daily work will most likely encompass basic techniques of molecular biology (DNA cloning, PCR etc), genetics (crossing flies and follow up progeny) and behavioural neuroscience (analysis of sleep, sleep deprivation, analysis of learning and memory performance).

Drosophila and neurobiology.

For decades, Drosophila has been the most powerful animal models for genetic dissection and manipulation, and the outstanding contributions that flies gave to developmental biology and genetics were celebrated twice with Nobel Prizes(1933, 1995), and countless time in our text books. Recently, more and more laboratories started pairing the incredible genetic tools that we have been building in the past century with new and exciting neuronal techniques, leading to a Drosophila neuronal renaissance. From circuit formation to their function, Drosophila offers the complexity of an animal that can learn, memorize, socialize and yet the accessibility of a 250 thousand neurons brain. Here, I link a few entertaining and informative videos with the aim to communicate the excitement this field is living right now.

• Gero Miesenboeck (Oxford). Engineering the brain (18 minutes TED talk)
• Michael Dickinson (Caltech). Towards an integrated view of brain function (28 minutes video)
• Bjoern Brembs (Berlin). The Drosophila Flight Simulator (3 minutes video)
• Charalambos Kyriacou (Leicester). An interview on the use of Drosophila for studying circadian biology and behaviour (14 minutes video)

Getting in touch.

My office is in room 743 of the Huxley Building, in the South Kensington Campus.
Email and phone number are listed here. I’ll be happy to meet you and show you the lab, just drop me an email.

References and sample readings

1. Synaptic plasticity in sleep: learning, homeostasis and disease.
   Trends Neurosci. 2011 Sep;34(9):452-63. (pdf)
2. Waking experience affects sleep need in Drosophila.
   Science. 2006 Sep 22;313(5794):1775-81. (pdf)
3. Widespread changes in synaptic markers as a function of sleep and wakefulness in Drosophila.
   Science. 2009 Apr 3;324(5923):109-12. (pdf)