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Measuring cellular processes in microseconds gives biochemists new view of how diseases begin

person sitting in research lab

To better understand illnesses that originate in the body, including cancer as well as autoimmune and neurological disorders, WVU biochemists are examining a molecular process that can initiate disease in the cells of humans and other mammals.

Kevin Courtney, assistant professor in the Department of Biochemistry and Molecular Medicine in the WVU School of Medicine, is leading an investigation into how glitches during cellular self-cleaning can cause diseases affecting the body’s metabolism, its nervous system or even its genetic code.

Courtney explained that mammalian cells clean themselves regularly in a process called “autophagy,” in which cells remove their old or damaged parts and recycle useful components. 

When autophagy proceeds as planned, it keeps cells healthy. But when errors occur in the final “fusion” step, cells can accumulate damage that leads to disease.

Courtney’s team will gain a unique view by combining advanced fluorescence imaging with electrophysiology methods that allow them to observe cellular events in living cells on a microseconds scale.

“This will be the first time anyone has used this cutting-edge approach to study autophagy at such a fine timescale,” Courtney said. “We’re focusing on how two specific proteins regulate the fusion step of autophagy — when a cell component called the autophagosome merges with the lysosome, the cell’s recycling center.”

A $2.1 million grant from the National Institutes of Health supports the five-year study.

“Knowing how these proteins regulate the fusion process at the molecular level and understanding the human genetic mutations that disrupt fusion will give us crucial information for preventing a number of debilitating and sometimes fatal diseases,” Courtney said. 

“The goal is to primarily address diseases like amyotrophic lateral sclerosis, or ALS, while also having implications for other neurodegenerative diseases and cancer.”

The research team includes WVU undergraduate students Angelina Duriez of Martinsburg, Alexander Olivero of Huntington, Julia Austria of Morgantown and Connie Adkins of Shady Spring, as well as alumni Paige Tyra of Avon, Ohio, and Lillian Shields of Allentown, Pennsylvania. 

Courtney welcomes inquiries from prospective WVU graduate students and postdoctoral fellows interested in membrane trafficking, single-molecule biophysics, neuroscience and disease mechanisms.