Walter and Eliza Hall Institute researcher Dr Matthew Call has been awarded a $150,000 Victorian Endowment for Science, Knowledge and Innovation (VESKI) Fellowship by the Victorian Government to continue his novel studies of immune cell receptors and signalling.
Dr Call's research could signal the beginning of an entirely new strategy for treating immune diseases, using creative 'membrane mimic' technology to solve the structures of membrane-embedded proteins, The research has the potential to initiate the development of a new class of drugs for treating autoimmune diseases and preventing transplant rejection.
Dr Call is a joint-laboratory head, with Dr Melissa Call, in the institute's Structural Biology division. He has spent 10 years studying the immune system and immune cell signalling, focusing on the function and role of the portions of cell signalling receptors that are embedded within cell membranes.
Dr Call said the membrane-embedded portions of immune receptors constituted a significant 'blind spot' in the field. "We are interested in understanding how signalling events at the surface of a cell are transmitted to the inside of the cell," Dr Call said. "Our lab takes a different approach to many by actually looking at the parts of the receptor that are embedded in the membrane of the cell, and trying to learn more about their structure and how they fit together. We hope this will give us a more direct view of the kind of mechanical movements that take place within the cell membrane to transmit a signal across the cell boundary."
Dr Call joined the institute last year from Harvard Medical School, where he and his colleagues spent years developing highly specialised techniques to purify and assemble the receptors in 'membrane mimics' that help to analyse their structure. "We are using these structures to generate hypotheses about how things might move during signalling, then we can use other cellular and biochemical studies to test those hypotheses," Dr Call said.
He said the VESKI Fellowship would enable the lab to use this set of techniques to study the membrane embedded portions of receptors. "We are going to be studying 'stress' receptors on natural killer (NK) cells," Dr Call said. "When a cell has turned cancerous, is physically injured, or infected by a virus, it sends out a set of cell surface proteins that are a 'distress flag' to the immune system. The receptors we study recognise some of those flags and mark the cells as targets for NK cells."
The work is particularly difficult because proteins embedded in the fatty cell membrane are oily and sticky, and can't be manipulated using standard techniques. "One of the problems with the field is that the proteins are really difficult to work with," Dr Call said. "They are difficult to make, they are difficult to purify and, even when you've done that, it's difficult to know what to do with them to identify their function."
Dr Call said that targeting the movements and interactions that take place within the cell membrane could generate a whole new class of drugs. "Most drugs do one of two things: they either target something on the outside of the cell, or the drug crosses the cell membrane and inhibits something going on within the cell. But there is an entire class of molecules that like to live within the fatty cell membrane and we are starting to look at the parts of proteins that sit inside the cell membrane as potential drug targets of the future."
Institute director Professor Doug Hilton said the VESKI Fellowship provided an excellent opportunity to recruit outstanding international researchers to Australia. "Dr Call's research is at the frontier of the structural biology field," he said. "The new ideas and techniques that Dr Call has brought to this area are unique in the world."
|Contact: Liz Williams|
Walter and Eliza Hall Institute