John McLean, Vanderbilt University and Structural Mass Spectrometry
The advancing role of ion mobility MS in systems biology
At our Pittcon conference on Monday, March 9, 2015, we showcased the innovative work of Prof. John McLean of Vanderbilt University’s Center for Innovative Technology. Prof. McLean was named a Waters Center of Innovation partner in 2013.
Prof. McLean will provide an overview of work his laboratory has recently been focusing on, “Targeting the Untargeted: Structural Mass Spectrometry for the Analysis of Complex Samples in Systems, Synthetic, and Chemical Biology.”
Vanderbilt University is the site of one of the world’s largest installations of mass spec instruments – with close to 80 state-of-the-art instruments supporting the work of 2,000 scientists per year. Some of the most exciting and varied work with Waters MS systems is being performed under the direction of Professor John McLean.
Professor McLean’s research spans everything from diabetes to wound healing to breast cancer, but he’s here today to tell us specifically about his analytics work in translational research centered on individual organs and human-on-a-chip programs.
Professor McLean and his team have built up expertise in the development of bioinformatic algorithms to sort through data and help researchers who are using mass spectrometry – and in particular, ion mobility – to discern complex biological signatures from massive molecular datasets.
Here’s more detail from the abstract of his discussion during our Pittcon press conference:
“One of the predominant challenges in systems-wide analyses is the broad-scale characterization of the molecular inventory in cells, tissues and biological fluids. Advances in computational systems biology rely heavily on the experimental capacity to make simultaneous broadscale omics measurements, i.e. integrated metabolomics, proteomics, lipidomics, glycomics, etc., accompanied with fast minimal sample preparation, fast measurements, high concentration dynamic range, low limits of detection and high selectivity.
“This confluence of figures-of-merit places demanding challenges on analytical platforms for such analyses. Ion mobility-mass spectrometry (IM-MS) provides rapid (MS) gas-phase electrophoretic separations on the basis of molecular structure and is well suited for integration with rapid (us) mass spectrometry detection techniques.
“Furthermore, the timescales of this multi-dimensional separation are well suited for combination with fast condensed-phase separations such as UPC2, UPLC and GC (min) for enhanced separation selectivity as the sample complexity becomes ever more challenging.
“This report will describe recent advances in IM-MS-based omics measurement strategies in the analyses of complex biological samples of interest in systems, synthetic and chemical biology. These strategies are described in the context of cutting-edge “human-on-a-chip” initiatives that utilize 3D primary human cell cultures to emulate organotypic function of the human.
“This new paradigm for drug toxicity and efficacy studies demands the extraordinary measurement capabilities afforded by integrated omics strategies, but places emerging challenges in rapid analysis of massive data.
“New directions in bioinformatics and biostatistics will be described to overcome these challenges from an unbiased and untargeted perspective and to quickly mine the data gathered to provide targeted and actionable information.”
Prof. McLean’s team also wrote a fascinating article for The Analytical Scientist in 2014,”Wound Healing in Diabetes: Applying an inclusive analysis that requires minimal sample manipulation to generate robust biomolecular signatures from diabetic wound fluid.”
See more of his group’s recent publications on their department web page.
About Prof. John McLean
John A. McLean is Stevenson Professor of Chemistry at Vanderbilt University. Prof. McLean completed his Ph.D at George Washington University in 2001, where he made significant contributions in plasma spectrochemistry in the development of new technologies for the analysis of complex and limited radionuclide and biological samples.
Subsequently, he performed postdoctoral research at Forschungszentrum Jülich in Germany and then as a postdoctoral at Texas A&M University with Prof. David H. Russell in biological mass spectrometry. Working with David Russell from 2001-2006, he constructed ion mobility-mass spectrometers capable of broad-scale omics analyses of complex biological samples, on the basis of both molecular structure and mass.
In 2006, Prof. McLean was recruited to Vanderbilt University as Assistant Professor of Chemistry through both the Department of Chemistry and the Vanderbilt Institute of Chemical Biology. At Vanderbilt, McLean and colleagues focus on the conceptualization, design and construction of structural mass spectrometers, specifically targeting complex samples in systems, synthetic and chemical biology as well as nanotechnology. His group applies these strategies to forefront translational research areas in drug discovery, precision medicine and “human-on-chip” synthetic biology platforms.
Prof. McLean has received a number of awards, including being designated a Waters Center of Innovation, an Agilent Thought Leader Award, Excellence in Teaching Award from the student members of the American Chemical Society, a Defense Threat Reduction Agency Research Award, an American Society for Mass Spectrometry Research Award, a Spectroscopy Society of Pittsburgh Award, an R&D 100 Award, and the Bunsen–Kirchhoff Prize from the GDCh (German Chemical Society), among others.