Maltese scientists have shown how the common fruit fly Drosophila, which is genetically and biologically similar to humans, could now be used to develop new therapies for the most common genetic killer of childhood – spinal muscular atrophy (SMA).
SMA causes death of the nerve cells (motor neurons) responsible for controlling body movement, slowly leading to muscle weakness and eventually causing death. The majority of the cases are due to an inherited flaw in the gene encoding for the Survival Motor Neuron (SMN) protein.
SMN is known to be intimate with a set of diverse proteins collectively termed as Gemins. The SMN-Gemins alliance is crucial for guarding against abnormalities in messenger RNA, the genetic mail carrier of instructions for building proteins.
Researchers from the University of Malta School of Medicine have been using the fruit fly as a model organism to study the biology of the SMN-Gemins family in brain and muscle. The latest results, published in the online, open-access journal Plos One have demonstrated that the disruption of the Gemin associates of SMN in either brain or muscle depresses the flight performance of flies, rendering them flightless.
Like any body movement in humans, active flight in flies is dependent on muscle capable of generating sufficient forces to offset gravity, and a controlling system provided by the brain to keep flies from tumbling to the ground. The expansive motor behaviour of flies has made them superb model organisms of neurodegenerative disease worldwide.
For the first time in Malta, the team has made use of DNA technology to generate flies that contain genetically-modified versions of the Gemin proteins. In this regard, the normal or mutant version of the proteins were fused to a glowing tag derived from jellyfish – green fluorescent protein (GFP) – to follow their movement within cells. GFP, which is an amazing cellular GPS, enabled researchers to track the otherwise invisible Gemin proteins to the cell nucleus or the vault containing the instruction manual for life – DNA.
Dr Ruben Cauchi, lead author from the University’s School of Medicine said: “We were crazy enough to use biotechnology tools to engineer, from scratch, normal and mutant proteins, and to generate genetically-modified organisms that can express these proteins in every single cell of their body.
“What motivates us? We are essentially curious, hungry for discovery, and have one mission – that of understanding one of the most catastrophic of diseases and its eventual eradication.”
“Our next step is to investigate whether the Gemin proteins, which remain undamaged in SMA, can functionally replace SMN. The fruit fly, which for more than a century has been a workhorse of genetics in the laboratory, is the only animal in which we can rapidly, economically, and effectively test this therapeutic strategy.”
The study, entitled The Gemin Associates of Survival Motor Neuron are Required for Motor Function in Drosophila, by Rebecca Borg and Ruben Cauchi, was partly funded by Malta Council for Science and Technology (MCST) through the National Research and Innovation Programme 2012 and was published in Plos One: http://dx.plos.org/10.1371/journal.pone.0083878