Dr. Gabriela Grigorean, (L) Senior Research Lab Specialist who manages the Orbitrap Fusion Lumos instrument, has significant expertise in both proteomics and metabolomics, and worked with Chemistry Professor Kristina Håkansson (R), the principal investigator on the NIH grant that made the purchase possible. photo: Suzanne Tainter

There’s a new mass spectrometer in town, and it’s being used by researchers in the Chemistry Department to study the molecular mechanisms of disease.

An Orbitrap Fusion Lumos mass spectrometer is now housed in the Department’s Mass Spectrometry Facility. The instrument is being used to measure proteins and metabolites to uncover the inner workings of cells.

Genome sequencing can provide clues about the causes of disease, but because genes are merely the template for the many proteins that actually perform biological functions, it is crucial to study proteins directly. Similarly, the makeup of metabolites, the small chemical products of life-sustaining reactions, can give an even more up-to-the-minute picture of a cell. Changes in the abundance or activity of proteins and metabolites can significantly impact biological function, and it is important for researchers to be able to detect such variations.

The Department obtained the instrument with a $1.1 million high-end instrumentation grant from the National Institutes of Health in 2016.

Before the Orbitrap arrived in 2017, the Chemistry Department did not have its own instrument for proteomics and metabolomics, experiments that profile proteins and metabolites. Now the Department has a mass spectrometer that is tailor-made for such ‘-omics’ studies. In a proteomics experiment, proteins from cultured cells or tissue samples are typically cut into pieces, or digested, with an enzyme. These protein pieces are then sprayed into the mass spectrometer, where they are precisely weighed. By measuring the protein pieces, the identity and abundance of the originating protein can be found. A proteomics experiment provides a snapshot of the protein landscape, and can help pinpoint disease-related changes in protein abundance and activity.

However, a major obstacle to getting an accurate picture of proteins or metabolites is their sheer complexity. The human body makes over 20,000 different proteins and more than 100,000 metabolites. Adding to the challenge, some of these are highly abundant while others are extremely scarce. In order to measure most of them in a reasonable amount of time, a mass spectrometer must be extraordinarily sensitive and tremendously fast. The Department’s new Orbitrap Fusion Lumos is the fastest and most sensitive mass spectrometer of its kind.

Users will also benefit from the prowess of Dr. Gabriela Grigorean, the new Senior Research Lab Specialist who manages the instrument. Dr. Grigorean was previously a Training Instructor for Orbitrap systems with Thermo Fisher Scientific. She has significant expertise in both proteomics and metabolomics, and even worked with Chemistry Professor Kristina Håkansson here at the University of Michigan for a brief period in 2005. Håkansson is the primary investigator on the grant that brought the Orbitrap to central campus.

Chemistry Professor Kristina Håkansson and Associate Professor Brandon Ruotolo were named "Thought Leaders" by Agilent. The Agilent Thought Leader Award promotes fundamental scientific advances by contributing financial support, products, and expertise to the research of influential thought leaders in the life sciences, diagnostics, and chemical analysis space. The award provides three years of financial support, along with Agilent instrumentation for ion mobility mass spectrometry, high-performance liquid chromatography, and sample preparation and introduction. The equipment donated by Agilent Technologies represents a significant financial contribution to the department.

"We are very excited to receive support from the NIH Office of Research Infrastructure Programs, along with cost sharing from various units at UM to cover service contracts and the addition of a PhD-level staff member to our mass spectrometry facility,” said Professor Håkansson. “We are working to further expand our capabilities and build state-of-the-art infrastructure to serve a wide range of applications and faculty research areas, both in the department and in the broader UM community."

Major users of the Orbitrap mass spectrometer are labs in Chemistry and the Life Sciences Institute headed by Philip Andrews, Katrina Håkansson, Robert Kennedy, Brent Martin, Brandon Ruotolo and David Sherman. Other users include Chemistry faculty Anna Mapp and Neil Marsh. Researchers in the College of Pharmacy, the Life Sciences Institute, and Molecular, Cellular and Developmental Biology will also use the new instrument for proteomics and metabolomics experiments.

The Orbitrap Lumos system is available to help conduct proteomics experiments by University of Michigan researchers outside the Department of Chemistry as well as those unaffiliated with the University. For more information, please contact Gabriela Grigorean at elagrig@umich.edu.