Structural biologists Drs Matthew and Melissa Call come to the institute from Harvard University, to lead a collaborative laboratory.
A chemistry set – a childhood gift from her grandmother – is likely to blame for Melissa Call’s scientific career. It inspired the journey out of her native Dunedin on New Zealand’s South Island to the University of Auckland, where she set her sights on biochemistry.
On gaining a coveted postdoctoral position at the Dana-Farber Cancer Institute in Boston, Call flew out to pursue her research career on a date forever etched not just in her memory but in history: September 11, 2001. She landed in Hawaii to news of the terrorist attacks and several days of delays before eventually being cleared into Boston in the shocked aftermath.
Soon after arriving at the laboratory she encountered Matthew Call, a PhD student from Dallas, Texas. He’d come to science via an adolescent fascination with wildlife, when he started reading journals to better maintain his menagerie of reptiles.
He figured he would become a medical doctor, but at university “I just fell in love with tinkering at the bench,” Matthew recalls. “Coming up with ideas, testing them, having few limits on what you can do appealed to me a lot more than the prescribed path of medicine.
“In 2001 I was one year into my PhD at the lab when Melissa joined,” he says. They were both interested in understanding the activation of immune cells, digging deep to look at the actual molecules that get triggered “to turn on the T cells and call them to go and kill pathogens. “We very rapidly and serendipitously got put together in an empty room, and found we got along very well.”
Melissa’s interest was in how molecular evidence of infection is displayed to T cells – the white blood cells that are the defence commandos that respond to invading pathogens. Matthew was studying the mechanics of the T cell receptor, which recognises these molecules. “So we were literally working at opposite sides of the same problem,” says Matthew.
Almost 15 years later, now married and also partners leading a laboratory at the Walter and Eliza Hall Institute, “in a very real sense that is still what we do – approach the same problems from different methodological sides”, he says. “We co-advise on everything, we write grants and papers together. Where we split is on the techniques we have expertise in.”
The Calls’ laboratory investigates how immune cells respond to external cues that control immune responses. Their focus is on the molecular structures and mechanisms used by sensors embedded in the thin fatty membrane on the cell surface, and how they pass information into the cell.
If they can decipher these communications, they will likely uncover ways the conversation might be therapeutically manipulated to change immune responses in cancer, infection and autoimmune diseases.
Much of their work so far has been in developing techniques to allow closer scrutiny of the communications and interactions in the “greasy bits” within the membrane. Breakthroughs on that frontier now crack open potential to advance further and faster.
“Just about everything that happens in the adaptive immune response – killing infected cells, producing antibodies, everything that vaccines are based on – is really centred on this event of activation of T cells through this particular set of molecules,” says Matthew. “So it is really the nexus of adaptive immunity. When we understand exactly how it is triggered, that opens doors to ways we can manipulate that for therapeutic use.”
“Inside the cell membrane has been a really challenging place to study the structure of proteins, because everything is embedded in oil, and most of the chemistry that has been worked out to study these molecules has been worked out in aqueous environments,” says Melissa. “We are developing or adapting techniques to be able to solve the structures of these membrane-embedded portions which we think are where important changes occur when T cell receptors are triggered.”
The move to the Walter and Eliza Hall Institute came when, shortly after determining that they wanted to pursue their careers together, the couple passed through Melbourne while on holiday. With their postdoctoral work finishing up, they were sniffing the wind for jobs.
They visited Parkville in 2009 and found a huge hole in the ground. The foundations for the new institute building were being poured as they watched and the opportunity it signalled – through the expansion it would allow – sealed their fate. “It was really very fortuitous,” says Melissa.
The institute’s credentials resonated powerfully. “One of the most basic tenets of immunology, our field, came out of the Walter and Eliza Hall Institute”, explains Matthew. “That was Burnet’s clonal selection theory, which really laid the groundwork for understanding how individual lymphocytes [white blood cells responsible for immune response] with predestined reactivity towards some molecules can be selected in the immune system”.
Melbourne was also by then home to Professor Peter Doherty, whose discoveries with Rolf Zinkernagel about cell-mediated immune defence also defined the field – and won a Nobel Prize.
The Walter and Eliza Hall Institute was “a great place to land” to pursue their scientific ideas, Melissa says. “We’ve been given a lot of flexibility. But there is also a real culture of working together. The institute is not really interested in recruiting great scientists who just work in their own little field. They really want to promote this culture of collaboration and cooperation.” They’ve partnered in projects in both the structural biology and infection and immunity divisions as well as pursuing their own program.
“I wouldn’t say it is any less competitive here in in the sense that there are very high quality researchers competing for diminishing resources,” says Matthew. “But the first instinct is to collaborate rather than compete, and that is really attractive.”
The Calls are representative of the recruitment and appointment of a number of younger laboratory heads at the institute by director Professor Doug Hilton. “I think a lot of outside institutions are waiting to see what happens next,” says Matthew. “And so are we.”