As the institute's centenary celebrations draw to a close we share one of more than 200 personal stories written for our award-winning Discovery Timeline centenary website. The website explores 100 years of discoveries through time, place, and most importantly, the people behind the science.

A childhood gift is likely to blame for Dr Melissa Call’s scientific career. A chemistry set from her grandmother inspired a journey that has led Melissa from Dunedin, New Zealand, to the Walter and Eliza Hall Institute, where she now heads a structural biology laboratory with husband and collaborator Dr Matthew Call.

Bright minds meet in Boston

Melissa gained a coveted postdoctoral position at the Dana-Farber Cancer Institute in Boston, US, and soon after arriving she encountered Matthew Call, a PhD student from Dallas, Texas. He’d come to science through an adolescent fascination with wildlife, when he started reading journals to better maintain his menagerie of reptiles. 

Matthew figured he would become a medical doctor, but at university found he gravitated to bench work. “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,” he said. 

"It wasn’t long before we found that we got along quite well!” 

 “I was doing my PhD when Melissa joined. We were both interested in understanding the activation of immune cells and serendipitously got put together in an empty room. It wasn’t long before we found that we got along quite well,” Mathew said. 

Two sides of the same problem

Melissa’s interest was in how molecular evidence of infection displayed to T cells – the white blood cells that are the defence commandos that respond to invading pathogens. Matthew, on the other hand, was looking at the mechanics of the T-cell receptor, which recognises these molecules. “We were literally working at opposite sides of the same problem,” Mathew said. 

“We were literally working at opposite sides of the same problem.” 

Almost 15 years later, this is in a sense still what Matthew and Melissa do – approach the same problems from different methodological sides. “We co-advise on everything, we write grants and papers together. Where we split is on the techniques we have expertise in,” he said.

An inspired move to Melbourne 

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 in 2009 while on holiday.

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,” Matthew said. “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”. It also won him a Nobel Prize.

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 of the cell surface, and how they pass information into the cell.

Deciphering the code

If the Calls 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.

“Just about everything that happens in the adaptive immune response – killing infected cells, producing antibodies, everything that vaccines are based on – is really centered on this event of activation of T cells through this particular set of molecules, so it is really the nexus of adaptive immunity,” Matthew said.  

“When we understand exactly how it is triggered, that opens doors to ways we can manipulate it for therapeutic use,” he said.

A collaborative calling

“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,” Melissa said.

“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,” she said.

“The first instinct is to collaborate rather than compete.” 

Both Matthew and Melissa reflect that the institute was a great place to land to pursue scientific ideas. “The first instinct is to collaborate rather than compete, and that is really attractive,” Matthew said.