• Sunday, March 03, 2024
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How a simple fungus paved the way to the Nobel Prize

A  technician with GE’s Delta Vision Elite microscope. (GE Healthcare Life Sciences)
A technician with GE’s Delta Vision Elite microscope. (GE Healthcare Life Sciences)

Recycling has been an essential human activity ever since early cave  dwellers fashioned new tools from flint and bone reclaimed from old or broken implements.

You could even say that it is in our genes. Take, for example, autophagy, the process living cells use to deconstruct and reuse their broken or worn-out components.

Juleen Zierath, a biologist at Sweden’s Karolinska Institute and a  member of the Nobel Committee for Physiology or Medicine, says that humans  need to replace up to 300 grams of protein in our bodies every day. Yet we  only eat on average about 70 grams of protein a day. The rest is salvaged in  cells through processes like autophagy. “Proteins are recycled with this  sophisticated machinery so that we can sustain and survive,” Zierath said in  an interview.

Much about autophagy, which occurs in life as diverse as mammals and single-celled yeast, remained a mystery until Japanese cell biologist Yoshinori Ohsumi started exploring it in the 1990s. His biological detective work won him the Nobel Prize in Physiology or Medicine in October. In recent years, Ohsumi used for his research a ground breaking microscope made by GE Healthcare Life Sciences.

This research laid the foundation for the team’s later work, which  relied on the increasingly sophisticated microscopes that became available  and allowed scholarly work on autophagy to explode.

Understanding autophagy is important because cells can’t survive  without it. In addition to replenishing the raw materials they need to build  new proteins and structures throughout an organism’s life, the process also  plays a critical role in clearing damaged proteins that can become toxic when  allowed to accumulate. Autophagy is also an important part of our immune  system, neutralising and dispatching invading pathogens, and it plays a role  in diseases such as cancer, Parkinson’s and Alzheimer’s diseases.

Before Ohsumi started working on autophagy, “the machinery was  unknown,” Zierath said. “How the system was working was unknown. And whether  or not it was involved in disease was unknown. Dr. Ohsumi was interested in  problems that other investigators stayed away from.”

In the late 1990s, Ohsumi needed to resolve smaller and smaller  structures to advance his research, and he started bumping against the limits  of the microscopes he had available. Also, pumping more light into the  microscope to resolve finer details can create heat that can kills cells. “At  the resolution Ohsumi’s lab was working at, the question becomes ‘Are you  watching biology in action, or are you watching a microscopic egg fry?” said  Paul Goodwin, the science director at GE Healthcare Life Sciences.

In 2001, in order to move forward, Ohsumi’s team began employing a  state-of-the-art fluorescence microscopy system called DeltaVision, which was  later bought by GE Healthcare Life Sciences. The system handles biological  materials much more gently, allowing researchers to record clear, highly  magnified time-lapse images of biological processes as they occur. With this,  Ohsumi’s group could start seeing the specifics of how vesicles called  autophagosomes form around the cell’s contents and fuse with the yeast’s  vacuole. This is the part that produces enzymes capable of breaking apart  larger molecules. That’s also where the proteins responsible for autophagy  localise over time.

The next step for this kind of research probably involves  super-resolution microscopy of yeast. In the super resolution space, GE Healthcare  offers the DeltaVision OMX SR, an advanced multimode, 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, Goodwin said.

“In biology, we often think about making things — DNA, proteins — but  we don’t think about what happens on the other end. And as important as  making proteins is, how they get broken down and reused is just as important  to understand,” Goodwin said. “Imagine if you could harness this process to  create new therapies. Imagine if you could disturb this recycling process  only in cancer cells and kill only them.”