The live-cell lattice light-sheet microscopy (LLSM) system developed by Nobel Prize winner Eric Betzig is a new technique that allows scientists to observe living cells at groundbreaking resolution. Dr McArthur traveled to the Janelia Research Campus in Virginia multiple times between 2015-2017, and remembers the moment when she witnessed, for the first time, the mitochondria actively expelling its DNA.
“As scientists, we are taught to be quite skeptical when we see something unexpected, so I think my initial reaction was ‘no way…’
“It was only after I had carefully repeated the experiment many times that I began to realize what we had found,” Dr McArthur said.
According to Professor Kile, when a cell commits suicide (a normal part of the human body’s balancing act to control blood cell numbers), two proteins called BAK and BAX are triggered.
“What we witnessed – in real time – was these professional killer proteins opening up huge ‘macro-pores’ in the outer membrane of the mitochondria, leading the inner contents to herniate out, bringing the mtDNA with it,” Professor Kile said.
“BAK and BAX deliver the ‘kill shot’ designed to permanently disable the cell. But in doing that, mtDNA is lost from the mitochondria. In essence, this is collateral damage, which, if it isn’t controlled properly, triggers the immune system to drive pathological inflammation,” he said.
The discovery was cemented by images captured by Monash University’s Titan Krios cryo-electron microscope, currently the most advanced microscope for biological electron microscopy, and the Walter and Eliza Hall Institute’s new lattice light-sheet microscope, custom built by collaborators in the Institute’s Center for Dynamic Imaging.
Professor Kile stressed that, in research, “fundamental discoveries such as this are rare, and this one has profound implications for the understanding of a wide range of autoimmune diseases and infections.
“This has been a brilliant collaboration – between Monash’s Bio-medicine Discovery Institute, the Walter and Eliza Hall Institute of Medical Research here in Melbourne and the Janelia Research Campus in the US – which has brought together cutting-edge technologies and first-class expertise to address questions that before now, had never been asked, and would have been impossible to answer,” he said.
Monash University. (2018, February 22). DNA gets away: Scientists catch the rogue molecule that can trigger autoimmunity. ScienceDaily. Retrieved March 27, 2018 from www.sciencedaily.com