Ion channels are the facilitators of all cell biology, according to Jacqui Gulbis. And she should know. She's been studying them for 25 years.
The Melbourne-based WEHI researcher is a leading expert on how the tiny, gated protein pores help regulate heartbeat, transport nutrients, activate t-cells, and allow nerve impulses and muscle contractions.
She's just as well versed on their impairment too, and its implications for the development and spread of conditions like epilepsy and diabetes as well as some cancers.
One thing Dr Gulbis and her colleagues haven't been able to explain, though, is why ion channels have for so long loomed as a prospective key to fighting disease, yet proved such a struggle for medical science to exploit.
That is, until now.
She and fellow scientist Brian Smith, an expert computational chemist with La Trobe University, have unlocked the mystery - or perhaps more precisely, opened the molecular gate which controls the flow of crucial potassium ions across cell membranes.
While conceptual, their breakthrough resolves a decades-old problem of understanding how potassium conduction is regulated by the body in order to transmit electrical signals essential for life.
Potentially, it also overcomes a major barrier to the development of life-saving drugs.
Potassium conduction is usually tightly controlled but goes awry as a result of some medical conditions, Dr Gulbis explains.
It's something science had been unable to figure out until she and Professor Smith overturned the widely accepted theory that potassium channels needed to physically widen in order to allow ions to cross membranes.
Then, using data collected at Melbourne's Australian Synchrotron research facility and other biophysical methods, they were able to show how the process actually worked.
They found that specific fatty lipids from within the cell membrane itself were instead interacting with the channel to allow the ions to squeeze through extremely narrow openings.
"In this new study we have identified 'the gate', described its nature and showed how specific membrane lipids engage with the channel to operate it," Dr Gulbis said.
"Not only is the gate in a different place than previously thought, it operates by a subtler and completely different process.
"Once you see it, it's obvious."
While true, getting there wasn't quite as easy as it sounds, according to Prof Smith.
"We used millions of hours of high-performance computing to run mathematical simulations to make this discovery," he said.
Part of the process also involved accessing the country's pre-eminent computing facility at the Australian National University in Canberra.
Prof Smith hopes the research will reignite the search for pharmaceuticals that target ion channel deregulation to treat diseases.
It's a quest which has been in hiatus for more than 20 years, Dr Gulbis says, because drug companies have been "labouring under a folkloric conviction as to how these ion channels work".
