Metabolomics and Mass Spectrometry
Our group is using mass spectrometry approaches to discover and validate biomarkers which are implicated in autism. This involves screening of human urine samples and developing quantitative approaches (using isotopic labeling or other chemical labeling) to determine levels of specific metabolites, including the tetrapyrrole stercobilin. The approaches are also being extended to screening fecal material excreted from transgenic rodents used as a model of autism. In addition, because of the high mass accuracy capability of the Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, we can deduce molecular compositions and (with MS/MS) structures of unknown metabolites. Additional metabolomics research in our group is focused on metabolites found in soybeans.
Current Students Involved:
Emily Sekera, Kevin Zemaitis, Erin Thiede
Imaging Mass Spectrometry, IMS
Using MALDI, it is possible to interrogate the surfaces of tissues (animal and plant) and examine their spatial distribution and even three-dimensional distribution. Our group is developing two-dimensional sheets to help improve the spatial resolution of imaging MALDI mass spectrometry and to extend it to less polar analytes than those currently accessible with traditional MALDI matrixes. Applications of MALDI imaging in our laboratory include distribution of substances delivered directly to mouse brains, distribution of molecules throughout the brains of mouse models of autism, models of demyelination/remyelination in spinal cord, and in plant metabolomics, with a focus on examination of how the aging of a plant leaf throughout a season can be tracked via MSI.
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A new aspect of our research involves the creation of a desorption electrospray ionization (DESI) source that can perform spot profiling of tissue sections. Our source was developed in part with 3D printing technology. A future aspect is to extend this to imaging, both alone and coupled with MALDI MSI.
Current Students Involved:
Kevin Zemaitis, Emily Sekera, Alexandra Izydorczak
Low-Flow Microreactors for Proteomics
Our group has made significant contributions in the development of miniaturized emitters for low-flow electrospray ionization. Our focus has turned to coupling such devices with enzyme microreactors for extremely rapid proteolysis and proteomic analysis. Such microreactors are stable for a period of months. We couple these devices with high-resolution FT-ICR for unparalleled analysis of proteolytic peptides. One application of our work is obtain sequence information from ancient proteins from fossils in the field of paleoproteomics. In addition, such microreactors can be utilized to obtain higher-order structural analysis when combined with hydrogen-deuterium exchange (HDX) or x-ray Footprinting.
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Current Students Involved:
Emily Sekera, Connor Gould