Research News

Neurosciences researcher Nikhil Panicker, PhD, and his lab are advancing discovery about basic signaling pathways and a lesser understood signaling complex in the brain’s immune cells: inflammasomes.

While scientists have known about inflammasomes for the past decade, effects of their activation in response to a detected threat are still unexplained. A fundamental discovery from the Panicker Lab highlighted how immune cells react unconventionally after inflammasomes assemble, and the team is now setting out to explore the downstream effects of that reaction.

Inflammasomes: ‘Alarm systems’ in immune cells

Inflammasomes are molecular “alarm systems” inside immune cells that activate when they sense infection or stress. In most parts of the body, like the blood or immune cells outside of the brain, inflammasomes assemble when they detect a threat and activate a protein that punches holes in the membrane of the dangerous cell.

That cell then releases inflammatory signals that alert nearby cells to danger, and purposely dies. This process is meant to keep a pathogen from spreading.

Dr. Panicker’s team expected to see this interaction between inflammasomes and immune cells in the brain like microglia and macrophages. What they actually saw was quite different.

Unexpected behavior—a mitochondrial connection

The Panicker Lab observed that when inflammasomes assemble in the brain, they do not go to the cell membrane. Instead, they go to the mitochondria, or structures inside cells that generate energy to fuel the cell's biochemical reactions. The mitochondria then become damaged and are transported out of the cell—but are then absorbed by nearby cells.

“Our interpretation of this package–transport–absorb cycle is that it is amplifying signaling between immune cells,” Dr. Panicker says. “Mitochondrial transfer has traditionally been understood as a way cells support one another. Our work suggests that this same process may carry inflammatory information.”

Working together to understand the ‘why’

Funding from the National Institute of General Medical Sciences will allow the Panicker Lab to narrow in on basic discovery. Their work will enhance knowledge in the field about inflammasomes, as well as the process of mitochondrial transfer in the brain.

The team, led by Amanda Serapiglia, a graduate student in Dr. Panicker’s lab who is in the Biomedical Sciences Training Program at Case Western Reserve University, will collaborate with other researchers who have additional equipment and techniques that are needed for the study. Hod Dana, PhD, has a special two-photon microscope in his lab that applies advanced fluorescence with lasers that excite molecules in living tissue. With this microscope, researchers will be able to observe the mitochondrial transfer in brain tissue. In addition, Dr. Panicker will use a red fluorescence technique to label and track the mitochondria, building on previous research from Justin Lathia, PhD, about mitochondria in glioblastoma.

“Collaborating with colleagues like Hod and Justin, who bring the expertise we need to do this research, proves that the sum of our strengths is more than the sum of its parts,” Dr. Panicker says. “Most importantly, the work we’ll get to do through this grant has the potential to challenge existing beliefs in our field.”