30 Jan New mass spec method gets the ‘nMOST’ out of multiomics data

Lysosomes (pink) are cellular organelles responsible for recycling biomaterial within the cell, shown here interacting with mitochondria (green). Image credit: Felix Kraus/Harper Lab, Harvard Medical School.
Biological systems are complex and highly regulated. A single genetic mutation can make all the difference in whether molecules function as part of a fine-tuned machine or if it will impair the system.
To better understand these underlying mechanisms that can lead to disease, scientists need reliable and efficient tools to collect and analyze -omics data — an integrated approach to studying different subsets of biomolecules.
In new research published in Science Advances, a team of researchers developed a method that uses nanoflow-based multiomic single-shot technology (nMOST) to profile both proteins and lipids simultaneously.
The collaboration was led by Joshua Coon, the Thomas and Margaret Pyle Chair in metabolism at the Morgridge Institute and UW–Madison professor of chemistry, and Wade Harper, department chair of cell biology at Harvard University Medical School.
The Harper Lab studies the molecular pathways involved in neurodegenerative disease, while the Coon Lab develops mass spectrometry and multiomics tools to investigate fundamental questions in cell biology.
“We were delighted to work with the Harper Lab to test and harden our new technologies and couldn’t be more delighted with the outcome,” Coon says.
This study used nMOST to assess lipids and proteins associated with lysosomal storage diseases. Lysosomes are organelles involved in the breakdown and recycling of biomolecules within the cell, like biological trash compactors. Mutations in certain proteins can impair lysosomal function, leading to the accumulation of cellular material in the organelle.
“If the trash system doesn’t work, a lot of stuff accumulates in the cell,” says Felix Kraus, a postdoc in the Harper Lab and co-first author of the paper. “It blocks the recycling and turnover of cellular material, which then causes the cells to be unhappy.”