Magnifying wonders

Linda Clarke Monday, February 10, 2025

Estimated read time: 0 min

Research Associate Meiling Zhu depends on the Olympus 1X70 microscope for experiments she conducts in Professor Emeritus Karl Insogna’s lab.

To the untrained eye, a look at cells through a light microscope might call up a memory from an early science class when the magnification of tissue on a slide felt wondrous. But to the experienced eye of Research Associate Meiling Zhu, the cells are part and parcel of experiments that could lead to new medical treatments for osteoporosis. Successful cell experiments might eventually result in clinical trials.

Zhu uses the Olympus 1X70 microscope in her work in the Anlyan Center labs, where she studies osteoclast cells that break down bone and are vital for bone health. Microscopy enables Zhu to see in detail the osteoclasts’ structure and behavior.

The computer-controlled microscope has a Hoffman modulation contrast objective lens that gives Zhu the chance to observe cells in three dimensions in real time. The microscope can also microinject cells and use fluorescence to image cells that have been dyed in certain ways. Its imaging capabilities —taking a static image, measuring its area, taking another static image and comparing its area to the first — have resulted in a method to quantify the cell volume and area of authentic, freshly isolated osteoclasts.

desktop computer screen displaying magnification of osteoclast-like cells — The magnification of these osteoclast-like cells on the computer screen is exactly what Zhu sees through the microscope.

The experiments that Zhu conducts are part of the work she does as a 21-year-long member of the research team of Karl Insogna, MD, Ensign Professor Emeritus of Medicine (Endocrinology) and an internationally recognized expert in the field of metabolic bone disease. Insogna is a leading researcher in the causes of bone loss in osteoporosis and hyperparathyroidism.

His lab concentrates largely on the process by which one hormone, the parathyroid, regulates bone formation and breakdown. In response to this hormone, cells build bone and make the Colony Stimulating Factor 1 (CSF1) molecule, which has a leading role in stimulating the osteoclasts’ ability to move.

images of osteoclast cells — 15 minutes after treatment with CSF1.

“Osteoclasts are cells that move along the bone surface like Pac-Man,” said Insogna. “They eat the bone to get rid of what is old and damaged — a critically important function because we need to renew our skeleton by removing the old bone and then putting down new bone.”

“The reason we focus on this,” he added, “is that when women reach menopause and lose the benefits of estrogen, their osteoclasts go bonkers and start letting go of more bone than they’re gaining. So, we are interested in the role of CSF1 in regulating osteoclast activity. Meiling is expert at using our microscope to investigate authentic osteoclasts and study their movement.”

The magic of microscopic eyes

reflection of osteoclast-like cells in a microscope lens — Reflected in the microscope’s lens is the osteoclast-like cell that Zhu is studying in the lab.

What is invisible to the naked eye is what Zhu relies on to run her experiments, which begin in the lab right around the corner from where the microscope resides. One of her investigations involves isolating live osteoclasts from bones that are chemically digested and purified in an incubator. Before the nutrient-rich culture is placed in the incubator, Zhu mixes the medium in a sterile environment.

The cells stay in the incubator until all the required slides are prepped in different mediums and are ready to go to the microscope. The osteoclasts are a tiny fraction of the cells in bone and locating them is akin to finding a needle in a haystack. Once Zhu identifies a live osteoclast, she uses the microscope’s magnification to precisely position it. Working quickly (osteoclasts do not live long), she uses the microscope to find other viable cells.

She then uses a computer driven stage on the microscope to return to each cell and observe its response to CSF1 alone, or after injecting the osteoclast with a molecule that is suspected of playing a role, in how and to what extent, the cell responds to CSF1.

cells under a microscope lens — Cells in different mediums are set under the microscope’s phase contrast lens for Zhu’s observation.

“The microscope gives our research so much potential,” said Zhu. “We can check cell culture and cell growing conditions. And, while this work is often very complex, it is exciting when we get good results from an experiment. It is meaningful because what we do can improve lives and cure diseases.”