Breakthrough two-dimensional gel technology is leading researchers to the causes of male infertility and the development of effective male contraception
Researchers at the Australian Research Council Centre of Excellence in Biotechnology and Development, part of the School of Environmental and Life Sciences in the Faculty of Science and Information Technology at the University of Newcastle, are rapidly gaining ground on the mysteries of male infertility and progressing the development of a reversible male contraceptive based on their findings.
Using two-dimensional gel technology called Dige (2D fluorescence difference gel electrophoresis) developed by GE Healthcare, researchers at the university have identified key enzymes, including certain kinases, believed to have a major role in male infertility.
The discovery has led to further research toward developing a reversible male contraceptive, based on the premise that inhibiting key enzymes including kinases in the sperm causes infertility, and reintroducing them reverses the process.
Mark Baker, based at the centre's reproductive lab, said one of the primary goals of his research is to establish how kinases are regulated.
"A staggeringly high portion - up to 10% - of Australia's male population is infertile, and the rate is rising," said Baker.
"We want to know why, and to do that we're comparing samples of fertile and infertile sperm using technology that makes the process faster and more accurate than was possible even two years ago".
The centre is currently one of only two in Australia - and eight in the world - actively researching male contraception, and Baker cites GE Healthcare's Dige technology as the key to its rapid progress.
"What Dige allows us to do is take a look at multiple normal and infertile samples and quickly compare the differences in their protein profiles," he said.
"We use special fluorescent gels called CyDye to mark individual proteins in the comparison samples, effectively creating a gel matrix or map of each sample.
"By overlaying the maps of normal and infertile samples, we can quickly see which proteins are shared by both, which are present in the normal sample and lost from the infertile sample, and which are present in the infertile sample but not in the normal.
"We can then start looking at the causes for the differences".
Protein profiling technology like Dige is ideally suited to this type of research because sperm, like red blood cells, do not produce any new proteins.
"We can't use DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) based technology to study sperm or red blood cells, but we can study their mature protein profiles using Dige," he said.
"Because ordinary 2D gels are relatively inconsistent, we previously had to take up to 72 gel readings to compare samples, just to verify the accuracy of the readings.
"With Dige we can now conduct the same experiment with 12 gels and be far more confident with the level of accuracy.
"The time savings are enormous".
Baker said the technology also helps to eliminate false positives and false negatives in the research findings, further improving accuracy.
"There were instances before we started using Dige where perceived changes in the protein profiles were later confirmed as false - hence false positives, and likewise perceived inertness was later seen as change - hence false negatives.
With DIGE these instances have been all but eliminated, and any inconsistencies can be quickly re-tested".
Despite the newfound efficiency of the fertility research project, Baker believes it will be at least seven years before any medications or treatments would be commercially available.
The current research is part of a long list of successes at the centre; it has already conducted critical research into the causes of asthma using Dige, and has also made the technology available to outside researchers to give interested parties access to the latest available technology in their own fields.
Peter Simpson, general manager Australasia, GE Healthcare biosciences, said the two organisations had a long-standing relationship pre-dating GE's acquisition of Amersham.
"To date we have not only supplied equipment to various labs at the university but have also assisted with the development of research methodologies and undergraduate and post-graduate training.
"Now with the backing of GE Healthcare we have a larger pool of resources on which we can draw to support the university's work," said Simpson.
"In line with our community focus, GE Healthcare continues to support the groundbreaking work being done at the centre, ensuring our technology remains at the forefront of advanced protein and gene analysis research in Australia."
