A Florida State University chemist has been recognized for developing a new method of analyzing human genetics that will help to more accurately understand and prevent diseases.
Christian Bleiholder, an associate professor in the Department of Chemistry and Biochemistry, earned the American Society for Mass Spectrometry's Ron Hites Award for his laboratory's paper, "Top-Down Protein Analysis by Tandem-Trapped Ion Mobility Spectrometry/Mass Spectrometry (Tandem-TIMS/MS) Coupled with Ultraviolet Photodissociation (UVPD) and Parallel Accumulation/ Serial Fragmentation (PASEF) MS/MS Analysis," published by Journal of the American Society for Mass Spectrometry in 2023.
"Receiving this award is particularly meaningful, as it acknowledges everything my lab has accomplished over the past decade," Bleiholder said. "We anticipate that our new approach of analyzing proteins created by individual human genes will lead to valuable insights and enable novel therapeutic interventions for cancer, neurodegenerative disorders and infectious diseases."
The Ron Hites Award is presented annually for an exemplary paper published in the previous two volumes of the Journal of the American Society for Mass Spectrometry, the official journal of ASMS, recognizing a high-quality presentation of outstanding original research.
"This award displays the department's excellence in research programs as well as the leadership positions held by faculty in their respective fields," said Wei Yang, chair of the Department of Chemistry and Biochemistry. "An important aspect of our research program is advancing and innovating tools, methods, and strategies that push the boundaries of modern science. Dr. Bleiholder's work is a clear representation of this goal."
The paper's lead author, Fanny Liu, is a research faculty member in the Bleiholder Laboratory, which studies the structure and dynamics of human biological systems at the molecular level to better understand how and why people become sick. Coauthors include Mark Ridgeway, Christopher Wootton, Alina Theisen, Erin Panczyk and Melvin Park, research scientists with Bruker Daltonics, a close collaborator with the Bleiholder Laboratory and a leading global developer and manufacturer of scientific instruments. Coauthor Florian Meier is a junior professor of medicine at Jena University Hospital in Germany.
"It's well known that the human genome, or a person's complete set of DNA, is made up of around 20,000 genes," Bleiholder said. "However, it's less recognized that these genes generate hundreds of thousands of different proteins, each with unique functions, shapes, and roles in health and disease. Understanding the complexity of these proteins is a fundamental challenge in biology and is crucial for precision in medicine, drug development and early diagnosis of diseases."
The presence of only 20,000 genes has long perplexed scientists, as human biology is far more complex than this number suggests. The discrepancy is explained by each gene's ability to create several types of proteins called proteoforms. Due to technical challenges, only about 5 percent of all human proteoforms have been identified.
"Our work describes a new analytical approach that has the potential to identify and characterize proteoforms more precisely, including subtle differences that are often missed by conventional methods," Bleiholder said.
To overcome limitations, the Bleiholder Laboratory has developed a new analytical platform, leveraging the individual advantages of three different mass spectrometry techniques, which measure and characterize molecules based on their mass and electrical charge. Tandem-trapped ion mobility spectrometry separates molecules based on how they move within a gas then analyzes those molecules using mass spectrometry. Ultraviolet photodissociation uses light to isolate individual molecules from larger compounds for analysis, and finally, parallel accumulation-serial fragmentation tandem-mass spectrometry accelerates and enhances the sensitivity of mass spectrometry.
"My colleagues and mentors in the mass spectrometry community constantly inspire me and my work," Bleiholder said. "Alan Marshall - Robert O. Lawton Distinguished Professor of chemistry and biochemistry - and Michael Bowers - my postdoctoral adviser at the University of California, Santa Barbara, and distinguished professor of chemistry and biochemistry - have profoundly influenced me personally and professionally. My doctoral advisers, Béla Paizs, head of molecular structure elucidation at the Rosalind Franklin Institute, and Rolf Gleiter, emeritus professor of organic chemistry at Heidelberg University in Germany, taught me to tackle difficult problems creatively."
To learn more about research conducted in FSU's Department of Chemistry and Biochemistry, visit chem.fsu.edu. For more about work done in the Bleiholder Laboratory, visit chem.fsu.edu/~bleiholder.
