UB’s new mass spectrometer can accelerate discoveries of new drug targets and biomarkers

BUFFALO, N.Y. ­— Imagine if diagnosis and treatment for devastating conditions such as Alzheimer’s disease could be developed quickly by extensive profiling of protein signatures in human tissues.

This vision may not be far from reality, thanks to a state-of-the art mass spectrometer that arrived at the University at Buffalo Center of Excellence in Bioinformatics and Life Sciences (CBLS) last fall. Researchers and industry partners are already using it to develop treatments for various diseases, among other purposes.

“Mass spectrometers are typically used to identify unknown compounds via molecular weight to determine the structure of the molecules,” said Jun Qu, PhD., professor in UB’s Department of Pharmaceutical Sciences who serves as the group leader of the Proteomics and Bioanalysis lab in the CBLS.

“It enables us to accurately determine the concentrations of specific molecules within a sample,” he said. “Particularly, in proteomics, you typically already know what proteins are in the tissue, but you want to know what protein changed or how much it changed under certain disease states or drug treatments.”

Much faster and more sensitive technology

Over the past six months, Qu has been using the new mass spec, called the Orbitrap Astral, to assist with his microscaffold assisted spatial proteomics (MASP) strategy, which enables first-ever whole-tissue mapping at the proteomic level. It uses a 3D-printed microscaffold that is capable of mapping thousands of proteins across a whole-tissue slice with excellent quantitative quality.

“The mass spec will substantially enhance the novel proteomics techniques developed by us,” Qu said. “Not only is it much faster than previous mass specs, but it also has a sensitivity that is at least 100 times higher. Sensitivity is very important when you are studying disease biomarkers and potential therapeutic targets.”

Their initial test, conducted in December 2023, indicated that with this new technology, they could cover 70-80% of commonly expressed proteomes in human samples. And that could lead to an improved understanding of diseases such as Alzheimer’s and may eventually lead to better treatment, Qu said. His group is using the MASP technique for extensive and accurate mapping of the brain.

“Not that long ago, scientists and medical professionals thought that plaque in the brain caused Alzheimer’s disease,” Qu explained. “Researchers have since realized that plaque may not be the cause. Rather, it could be a symptom. A machine like this mass spec will enable the de novo discovery of the true mechanism of this intractable disease.”

UB a pioneer with Orbitrap Astral

UB is the first institution within the State University of New York (SUNY) to acquire the Orbitrap Astral. Created by the global scientific equipment company Thermo Fisher Scientific, the Astral has the ability to accurately quantify more than 8,000 protein groups from a single cell and analyze more than a million protein groups across 180 microscopic samples in a single day.

“We were among the top 10 institutions in the country to get this revolutionary equipment,” Qu said. “When Thermo Fisher realized we had the ability to map tens of thousands of proteins, they highly supported our early delivery. Many of the engineers that traveled here with the equipment had never seen it.”

Connecting UB with innovative industry partners

A New York State economic development grant funded the acquisition through UB’s Business and Entrepreneur Partnerships office.

“Access to emerging, next-generation technologies often stands as the primary barrier to groundbreaking discoveries,” said Venu Govindaraju, UB vice president for research and economic development. “By strategically investing in spatial omics technologies, UB is poised to lead pioneering research that catalyzes vital innovations, ultimately enhancing public health and, in critical scenarios, preserving lives.”

The Astral Orbitrap opens the door for exciting new discoveries and innovations that will make a positive impact on human health and elevate the research being conducted at UB, noted Smitha James, senior associate director of life sciences programs with the BEP.

“Having access to this advanced technology will place UB researchers in a much stronger position to compete for future grants,” James said. “In addition, the new acquisition is expected to drive increased industry collaborations and support of life sciences startups.”

Study of retina degeneration in smokers 

Qu, who has been studying whole tissue samples for the last few years, said he’s excited about the opportunities the new mass spec presents.

“We want to provide the research community with access to the best proteomics tool ever devised,” he said. “It offers unparalleled sensitivity, speed and exceptional depth for proteomics analysis.”

Currently, Qu and his team, including UB PhD and postdoctoral students Xiaoyu Zhu, Min Ma, Shihan Huo and Shuo Qian, are using the mass spec as part of a collaboration with researchers at the University of Minnesota on a study of retina degeneration in smokers. Already, Qu said, he can see a huge improvement in the number of quantifiable proteins, in terms of data quality and speed, as they try to determine the mechanism underlying the higher risk of retinal degeneration among smokers.

“If we used traditional biochemical technology, it might take decades to test each protein in a project like this,” Qu said. “Here, we take a very small sample, and we can quantify 10,000 proteins in seconds.”