Fly Genetics

There are 14,000 genes in a fruit fly, and probably only 23,000 in a human. One of the great shocks of the genetic revolution has been to discover how much genetic information is preserved across all life forms. Genome sequencing has changed everything. We are astonishingly closely related to mice, to flies, and even to yeast.

Seventy-five per cent of genes in humans that are associated with disease have a homologous gene—i.e. the same gene making similar protein and doing a similar job—in the fly.

Many genetic mechanisms that define cell signalling pathways or developmental processes are known to be conserved in the fly. It seems highly likely that key neural mechanisms that control behaviour in flies will also be preserved in other intelligent organisms, including humans.

Sophisticated genetic manipulations can be carried out on flies that cannot be carried out on any other multicellular organisms. These genetic manipulations allow us to ask questions about the behaviour of the organism, of individual cells, and of groups of cells.

The availability of the entire fly genome sequence makes the cloning or disruption of particular genes straightforward, and precise genetic tools for inserting genes into the genome are well established. The potential for removal, and especially for addition, of single genes or proteins is a key feature of why we use flies.

We use genetic address labels called promoters and enhancers to tell our manipulated gene to become active only in certain cells in the brain. We use this technique to control a wide variety of tools. We can label cells with fluorescent proteins, or with markers for electron microscopy. We can express mutant variants of endogenous genes, or constructs that disrupt function of particular target genes. We make extensive use of optogenetic tools, which can make particular cells light up when they are active, or become active in response to light. Other tools can manipulate the properties of neurons, for example blocking synaptic transmission at certain temperatures or altering electrical characteristics.

Addressing systems can also be constructed which highlight the intersection of two (or possibly more) groups of neurons, much as the location of a city block can be described by the intersection of two streets.

Taking all these approaches together, however, we still find that we sometimes fall short of precision in directing expression of genetic tools to the circuit elements of interest. Several research projects in the CNCB are directed towards solving this problem.