Single Molecule Science
One of the intractable mysteries of biomedicine is how our T cells – the ‘frontline soldiers’ we depend on to activate our immune systems – make the critical decisions that determine our health and wellbeing.
Overactive immune systems attack their own hosts, manifesting in conditions such as diabetes, arthritis and Crohn’s disease, while underactive systems fail to adequately protect against pathogens and cancers.
Although we know that the decision-making process is ‘read out’ across a large signalling network inside a cell, we don’t yet know how signals are generated and how information is processed across the network, says Scientia Professor Katharina Gaus. Consequently, we don’t know what’s going wrong when the immune system underperforms or overreacts.
Instead of looking at this highly complex system from the top down, Gaus and her team are working from the ground up by trying to understand the rules that govern individual molecules.
Single molecule science isn’t just a road less travelled, “it’s a road not travelled at all in terms of scientific discovery”, she says.
“It seems paradoxical to study a complex system by investigating individual molecules, but if we discover the molecular rules then that complexity, or chaos, is reduced to the few rules that are unique to each molecule.”
Parallels can be seen in the animal world. Ants form highly organised and resilient systems despite having no one ant in charge. The insects’ behaviour is determined by innate rules that each ant follows, allowing them, for example, to form an “ant highway” directly to food.
Whether it’s ants or single molecules, the rules governing the individual elements illuminate how the whole system works, Gaus says.
The single molecule science that Gaus is pioneering has been made possible through significant advances in imaging and the development of a new generation of super-resolution fluorescence microscopes that allow researchers to see even a single copy of protein within a living, intact cell. Understanding the incredible potential, Gaus has built a lab of the new microscopes at UNSW, which is the Australian node of the European Molecular Biology Lab (EMBL).
The goal is to create a new class of drugs that can alter the rate at which molecules interact to recalibrate compromised immune function.
In a world-first result, described in Nature Immunology in 2013, Gaus and her team at UNSW’s EMBL Australia Node in Single Molecule Science identified a kinase protein that ‘yo-yos’ in and out of clusters. They proposed that the rate of this dipping in and out determines how quickly a signal is generated, a critical step towards understanding the all-important rate of molecular interactions.
The work won Gaus the prestigious Elizabeth Blackburn Fellowship for Australia’s top-ranked female research fellow in biomedical science in 2013.
“What’s really exciting is that we are at the beginning of a new science. For me, being able to do research at the cutting edge is an absolute privilege,” she says.