Principal Supervisor: Professor Charalambos P Kyriacou, Department of Genetics and Genome Biology
Co-supervisor: Dr Ezio Rosato
PhD project title: Aggression in Drosophila
University of Registration: University Leicester
Aggression is a highly conserved phenotype that is found in all higher animals and remains arguably the greatest affliction of humanity. The genetic basis of aggression in humans was originally stimulated by the identification of a family pedigree in which a rare mutation in the monoamine oxidase A (MAOA) gene was implicated in borderline mental retardation and impulsive aggression1. A number of non-human model systems have also been studied in order to illuminate the genetic and environmental bases of this complex social behaviour, and the monoamines are prominent in mammalian2 and invertebrate aggression research, particularly in the crustacea3 Male Drosophila melanogaster can also be agonistic against other males, as documented in several studies4 Males demonstrate stereotyped behaviours that can be easily scored and analysed, and transcriptomics approaches, after successful selection from base populations for different levels of aggression have revealed many putative candidate genes. Not surprisingly perhaps, aggression which is much more dramatic in males is under the control of the sex determination system and octopaminergic, dopaminergic and 5HT subsets of neurons have been implicated in the neuronal network underlying this phenotype5-11.
We have used a unique paradigm to identify ‘Gandhi’ and ‘Rambo’ flies (peaceful versus hyperaggressive individuals) and have correlated their behaviour with gene expression. We find that the gene encoding Dopamine acetyl transferase (Dat), an analogue of human MAOA, has two splice forms, which when overexpressed give the Gandhi or Rambo phenotypes. The two splice forms are localised in overlapping regions of the brain that suggest a binary switch mechanism that controls fly aggression. We also have a number of other genes from our original paradigm that seems to have large phenotypic effects on aggression and we would like to develop some of these into PhD projects. We are writing up the work for a high impact journal (Nature Neurosci or Curr Biol).
The work will include behaviour, genetics and molecular biology, as well as confocal microscopy and possibly electrophysiology. Drosophila has the most sophisticated molecular genetic toolbox available for any organism and its application to a neurogenetic problem which involves the nervous system allows one to perform experiments that are almost impossible in any other model organism. Gene editing via CRISPR/Cas9 will also be applied to generate mutations in the relevant genes and determine their functional effects. Statistical and Bioinformatic techniques will be prevalent and the candidate will need excellent computer skills. In short, the project is highly multidisciplinary and transcends many different levels in biology and genetics, from the molecular to the behavioural (and almost every level in between).
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- Zhou C et al (2008) Nat Neurosci 11:1059-67
BBSRC Strategic Research Priority: Food Security
Techniques that will be undertaken during the project:
- Fly genetics and mutagenesis
- Behavioural analysis
- Neurogenetics – confocal microscopy, imaging