The internal clock that tells us when to wake up, when to eat and when to go to sleep might seem mundane, but it was the basis of research for this year’s winners of the Nobel Prize in Physiology or Medicine. Three scientists, Jeffrey Hall, Michael Rosbash and Michael Young won the prestigious award by unearthing the three genes that interact to regulate our circadian rhythms and showing how those rhythms connect to health problems like obesity, diabetes and cardiovascular diseases.
The trio joined an elite group of biologists whose fascination with the secret lives of cells also led them to Nobel Prize-winning discoveries in medicine or physiology. But they share more than just the Swedish award: 75 percent of recent winners of the Nobel Prize relied on a version of the DeltaVision microscope from GE Healthcare during their research. This year’s winners, for example, used it to “peek inside our biological clock and elucidate its inner workings.”
This type of “peeking” wasn’t possible up until 25 years ago. Researchers could not keep cells alive long enough to study their behavior. Once detached from their host bodies, living cells wither under the hot glare of the microscope. The DeltaVision solved that problem with an environmental chamber that mimics the temperature, humidity and other aspects of a body closely enough to keep living cells ticking for several weeks.
There are other benefits. A different DeltaVision product uses software and high-definition cameras to observe bacteria, viruses and other samples in 3D even beyond Ernst Abbe’s diffraction barrier, which limited microscopic resolution to roughly half the wavelength of the light the microscope used. The DeltaVision machine’s added resolution allows scientists to see more than they’ve ever been able to see with light microscopy, such as watching how biofilms form in real time, or viewing a cell’s nuclear pores or other subcellular structures.
The design also allows them to tag bacteria with fluorescent molecules and use them to illuminate hidden features. Paul Nurse and Lee Hartwell, who used one of the first versions of the machine, depended on this feature while doing their research into how cells divide. As the cells lived happily in the environmental chamber, the scientists were able to record clear, highly magnified time-lapse images of biological processes as they occurred. That work earned them the Nobel Prize in 2001.
Finding cell structures can be hard. In some ways, it’s like looking for a single back alley on a citywide map of Los Angeles. Elizabeth Blackburn, president of the Salk Institute and 2009 winner of the Nobel Prize, used the DeltaVision in her research on chromosomes. She was looking for telomeres — structures that protect the ends of chromosomes and are essential to understanding aging, cancer and other stem-cell disorders.
Blackburn found the telomeres by setting her cell sample on the DeltaVision’s automated stage, which lets the scientist use a joystick to scan the sample in three dimensions (marked by x,y and z axes). Viewing her specimen on a computer monitor, Blackburn was able to zero in on telomeres she found in much the same way one would use a Google map to zoom in on the right street address. She could then punch in the coordinates of her favorite spots, directing the digital camera to take continuous photos of those specific areas over a period of time. The microscope automatically stored the data to her computer so she could analyze it further.
Many of these breakthroughs may just be phase one for the Nobel laureates. For instance, Dr. Yoshinori Ohsumi, who won the 2016 Nobel Prize for his study of the protein’s recycling process, known as autophagy, also relied on an older version of DeltaVision microscope.
The next step for this kind of research will likely involve super-resolution microscopy of yeast, the cells of which share many properties with human cells. GE Healthcare’s latest version of the DeltaVision includes a super-resolution system that produces images in two and three dimensions. Advanced research in super resolution has the potential to unlock more of autophagy’s secrets and open new doorways to translate this basic science into disease treatment and prevention.
The Nobel Committee for Physiology or Medicine will surely be watching.