|
| FACULTY |
| Name |
Room |
Phone |
E-Mail |
| Baranov, Vladimir |
MDS SCIEX |
905-660-9005 |
vladimir.baranov@utoronto.ca |
| Bohme, Diethard K. |
260 CB |
*66188 |
dkbohme@yorku.ca |
| Fournier, René |
303 PS |
*30687 |
renef@yorku.ca |
| Goodings, John M. |
148 CB |
*33852 |
goodings@yorku.ca |
| Hastie, Donald R. |
305 PS |
416-736-5388 |
hastie@yorku.ca |
| Hopkinson, Alan C. |
248 CB |
*77839 |
ach@yorku.ca |
| McDermott, John C. |
327 FS |
*30389 |
jmcderm@yorku.ca |
| Pearlman, Ronald E. |
242 FS |
416-736-5241 |
ronp@yorku.ca |
| Rudolph, Jochen |
302 PS |
416-650-8117 |
rudolphj@yorku.ca |
| Siu, Michael |
242 CB |
416-650-8021 |
kwmsiu@yorku.ca |
| Thomson, Bruce A. |
MDS SCIEX |
905-660-9005 |
thomsoba@sciex.com |
| Derek Wilson |
237 CB |
*20786 |
dkwilson@yorku.ca |
 |
Dr. Bohme's research continues to focus on the investigation of metallic, organometallic and biometallic ion chemistry and has now expanded further into biological ions and ion chemistry. An inductively coupled plasma / selected-ion flow tube / triple quadrupole (ICP/SIFT/QqQ) mass spectrometer has been used to study bare metal-ion chemistry and two electrospray ionization (ESI)/triple quadrupole mass spectrometers are providing information on the breakdown of selected organometallic, biological and biometallic ions. Also, an ESI/q/SIFT/QqQ configuration has been developed to study reactions of small molecules with biological and biometallic ions, including positive and negative ions of penicillins, siderophores, porphorins, phthalocyanines and oligonucleotides. Further strides have been made in characterizing periodic trends in the reactivities of bare atomic metal and lanthanide cations towards a variety of small molecules (the data are available on our web site). Early measurements with the ESI/q/SIFT/QqQ have focussed on the protonation of highly-charged anions of a 6-mer oligonucleotide and the ozonolysis of metallated peptides, porphyrin and phthalocyanine. These measurements, along with others involving ligation of metals with small segments of biological molecules, show promise for mimicking of in vivo biological interactions and measuring their intrinsic reactivities in the gas phase.
In 2006/07, 29 refereed papers and book chapters were published by the Bohme group or are in press. Bohme has been invited to edit a series of issues in Mass Spectrometry Reviews that will highlight mass spectrometry in Canada (he has asked Bob Boyd to be co-editor). Talks were again presented by student members of the group at this year’s Ontario Ion Chemistry meeting in Orillia. Several members of the group also presented at the 55th ASMS Conference on Mass Spectrometry in Indianapolis in early June. Janna Anichina gave a talk entitled "Electrospray Ionization Mass Spectrometry of the Interaction of Oligonucleotides with Metals, Small Molecules and Drugs." Michael Jarvis was invited to speak at York University on April 26th to a group of visitors from Europe on "Searching for the Origins of Life in Interstellar Space". Bohme presented a plenary lecture at the 21st joint meeting of the mass spectrometry societies of New Zealand and Australia in Christchurch in January, 2007, entitled "Atomic Ions: the Ultimate Sites for Catalysis". While in Australia he also lectured on "Gas Phase Chemistry of Atomic Metal Ions" at the Dept. of Chemistry, U. Wollongong, on Jan. 29 and on "Gas Phase Chemistry of Atomic Metal Ions: from Atomic to Biometallic Cations" at the Dept. of Chemistry, Australian National University, Canberra, on Feb. 1. At the Gordon Conference in Ventura, CA (Feb. 26 - March 2) he presented an invited lecture on "Ions in Space" in a Symposium on Astrochemistry. Later on May 27th Bohme presented the CIC Medal Lecture entitled "Gaseous Ions and Chemical Mass Spectrometry" in Winnipeg at the 90th Canadian Chemistry Conference. On October 2nd he lectured on "Atomic Metal Ion Chemistry in the Gas Phase" to the Dept. of Chemistry, Memorial University, Nfld. Most recently, while guest professor at the Institute of Ion Physics and Applied Physics of the University of Innsbruck, Austria, in December, 2007, Bohme lectured on "Chemistry with Multiply-Charged Ions: from Atoms to DNA". |
 |
Dr. Fournier studies the geometric
structure of clusters by theoretical methods. The energy is calculated by
density functional theory (DFT) and is minimized by a new algorithm called
the "Tabu Search in Descriptor Space" (TSDS) developed by the Fournier
group. Clusters and molecular ions often have unusual structures that do not
obey the simple rules of chemistry textbooks. The current TSDS algorithm
systematically searches all kinds of cluster structures, without a priori knowledge or assumptions, so it is able to find unusual structures. A
Ph.D. student, Yong Wan, is modifying TSDS so that molecular ions can be
studied in the future. Another student, Min Zhang, is developing a
semi-empirical method to calculate, at a small computing cost (seconds or
minutes), atomic charges, ionization energies, and electrostatic potentials.
This method can treat neutral or charged systems containing up to thousands
of atoms with an accuracy nearly as good as DFT. |
 |
Dr. Hastie is interested in
mass spectrometric analysis of atmospheric particulate matter. There is a
robust connection between atmospheric particulate matter and adverse health
impacts. As part of the efforts in understanding the production and fate of
particulate matter, the Hastie group addresses the chemical identification
of the species present in the secondary particulate matter produced from the
atmospheric oxidation of gas phase hydrocarbons. This material is known to
be a significant contributor to atmospheric particulate mass, but its
toxicity cannot be properly studied until a more complete chemical
identification is done. The ultimate aim of this work is to actually
determine the chemical species produced in these oxidation reactions and
those that end up in the particle phase. The identification of these
compounds will permit identification of the source of particulate matter,
both in terms of the precursor compounds and the sector responsible for
their production. The methodology involves producing atmospherically
relevant particulate matter in the laboratory from the controlled oxidation
of gas phase hydrocarbons, and analyzing the products using mass
spectrometry. |
 |
Dr. Hopkinson's research is in the area of
application of computational chemistry to the calculation of ion structures
and energetics. The bulk of his research has been carried out in
collaboration with Professors Bohme and Siu. These calculations are crucial
to mass spectrometry research as they provide plausible structures and
energetics of experimentally measured ions and transition states involved in
fragmentation pathways. These allow fragmentation mechanisms to be proposed
and ion chemistry rationalized. Ions that have been examined range from
dipositive and tripositive metal-centered ions, protonated and metalated
oligopeptides, polysodiated ions, and peptide radical cations. |
 |
Dr. McDermott's
mass spectrometry-related research centers on the phosphorylation status of
an important protein, myocyte enhancer factor (MEF) 2A, which is a member of
a family of transcriptional regulators recognized for heart and skeletal
muscle development and in the protection of neuronal cells from apotosis. In
the last year, several novel phosphorylation sites on MEF2A were identified,
and significant advancement in the understanding of MEF2A regulation was
also made. These constitute the basis of a collaboration with Stratagene, La
Jolla, CA, on the development of tandem affinity purification for producing
significant quantities of proteins for mass spectrometry characterization. |
 |
Dr. Pearlman's mass
spectrometry-related research has continued to focus on the development of
proteomics approaches with the model eukaryotic microorganism, the ciliated
protozoan Tetrahymena thermophila. This work has been carried out in
collaboration with Dr. Siu. A major emphasis of these studies has been on
the analysis of proteins of cilia, an important organelle present in many
eukaryotes including metazoans (e.g. human) but not present in another model
eukaryotic microorganism, the yeast, Saccharomyces cerevisiae. Data
were obtained by LC/MS/MS analysis of isolated and purified cilia.
Initially, protein identification was based on analysis of an in-house
database of translated expressed sequence tags (ESTs) from a pilot
EST-sequencing project (Genome Canada, Pearlman co-PI) as well as MS-BLASTing
against complete GenBank databases. The complete but unannotated Tetrahymena genome sequence was released in October, 2003 (NIH and NSF
funded, Pearlman-co PI). New bioinformatic analysis approaches have been
developed to analyze whole organelle MS/MS data and this has accelerated and
facilitated protein identification and functional analyses. To date, 285
ciliary proteins have been identified. Other Tetrahymena organelle
proteomics is also underway. Analysis of the phagosome proteome is ongoing,
in collaboration with Dr. Lawrence Klobutcher, University of Connecticut
Health Sciences Center. Phagosomes are another organelle with very important
function found in metazoans including humans but not in S. cerevisiae.
Examination of the mitochondrial proteome has been initiated, in
collaboration with Dr. Michael Gray, Dalhousie University. This project will
provide important comparative information as essentially no data on the
complete mitochondrial proteome of any protist exist. These efforts have
already resulted in identification of hundreds of proteins in phagosomes and
mitochondria. In addition, a proteomic approach to the analysis of regulated
secretion in Tetrahymena has also been initiated, in collaboration
with Dr. Aaron Turkewitz, University of Chicago. A comparative proteomic
analysis of Tetrahymena nuclei has also begun. The focus of this work
will be to identify proteins specifically involved in developmentally
programmed genome rearrangement. Furthermore, whether methylation at lysine
residues occurs in an important nucleolar protein involved in ribosome
biogenesis in Tetrahymena is also currently being addressed. |
 |
Dr. Rudolph is interested in characterization of
secondary organic aerosols (SOAs), in particular the use of stable carbon
isotope ratios in identifying their origin. Measurement of the isotope ratio
of SOA formed by the photochemical oxidation of toluene in a flow reactor
showed a significant fractionation between toluene and the formed secondary
particulate organic matter. The observed isotope fractionation is consistent
with a fractionation solely due to the kinetic isotope effect for the
reaction of toluene with the OH-radical. Independent of the origin of the
isotope fractionation between precursor and SOA, the results strongly
suggest that the isotope ratio of the SOA depends on the degree of
processing of the gas-phase precursor. It can therefore be expected that
measurement of the stable carbon isotope ratio of ambient SOA will allow
differentiation between recently formed and old SOA. This can be used to
differentiate between SOA formed locally and SOA from long range transport.
Isoprene is one of the most important organic compounds in the atmosphere
and a main contributor to photochemical air pollution. Although atmospheric
isoprene is predominantly due to emissions from vegetation, understanding the role of isoprene is essential for the development of
effective pollution control strategies. Combining concentration with isotope
ratio measurements is a very powerful tool to determine study the sources
and chemistry of isoprene in the atmosphere. |
 |
Dr. Siu's
group continues to tackle a
variety of subjects ranging from the very fundamental to the very applied. A
series of studies have been carried out to examine the fragmentation
chemistries and mechanisms of protonated peptides; fragmentation of
protonated peptides constitutes the backbone in protein sequencing and
identification in proteomics. Much progress has been made in exploring and
understanding the structure and dissociation mechanisms of molecular radical
cations of peptides, after an unprecedented method for producing these
fascinating species were discovered by the Siu group in 2000. Binding
chemistries of peptides to metal ions have also been examined in detail.
These investigations were carried out experimentally and theoretically in
collaboration with Professor Hopkinson. Much inroad has been made in
building and applying new mass spectrometric hardware for innovative
studies. These were carried out in collaboration with MDS Sciex scientists,
including Drs. Thomson and Baranov. A custom-built triple quadrupole mass
spectrometer having a high-pressure segmented second quadrupole has been
used for characterizing metallothioneins and examining the effects of
methylation, an important protein posttranslational modification. A similar
instrument, but one that is based on a commercially available triple-quadrupole
mass spectrometer, was utilized for examining ion-molecule reactions. A
hybrid quadrupole/time-of-flight mass spectrometer has been modified for
infrared multi-photon dissociation; initial results in application to
top-down sequencing of proteins have been encouraging. A number of
collaborative proteomic projects with biologists and biomedical scientists
have resulted in significant findings. In collaboration with Dr. Terence J.
Colgan, Mount Sinai Hospital, and Dr. Alexander D. Romaschin, St. Michael’s
Hospital, a total of 15 potential protein markers for endometrial cancer have been discovered and identified; some of these have been independently
verified using immunohistochemistry and tissue microarrays. In collaboration
with Professor Pearlman, 285 ciliary proteins have been identified in Tetrahymena thermophila, a model organism whose genome sequence was
released at the end of 2003 (see above); collaborations with other
researchers in mapping the proteins in other organelles are ongoing. In
2004/05, 28 refereed papers and book chapters have been published or are in
press (5 others have been submitted and are in review); 49 presentations
were given by Siu and his group. Thirty of the presentations were invited,
including presentations at academic institutions (University of Toronto,
University of Alberta, University of California Davis, St. Francis Xavier
University, McMaster University, and University of Hong Kong), hospitals
(Princess Margaret Hospital and Sunnybrook and Women’s College Health
Sciences Centre), conferences (American Society for Mass Spectrometry, Trent
Conference on Mass Spectrometry, Federation of Analytical Chemistry and
Spectroscopy Society Conference, Lake Louis Tandem Mass Spectrometry
Workshop, Asian Conference on Analytical Sciences, International Conference
on Analytical Sciences and Spectroscopy, Proteome Society Meeting, Human
Proteome Society Annual Conference, Canadian Society for Pharmaceutical
Sciences Annual Symposium, Toronto Biotechnology Initiative Symposium,
Progress in Systems Biology Symposium, and Annual Workshop on Innovative
Research Group of Persistent Toxic Substances), and industrial symposia
(Applied Biosystems / MDS Sciex Life Science, Proteomics, and Biomarker
symposia). |
| |
Dr. Thomson’s is centered on developing new tools to combine with mass spectrometry for the improved analysis of biomolecules. Work has continued on interfacing an infrared laser to a QqTOF for improved fragmentation and desolvation. IRMPD has previously been shown to be able to fragment proteins, and now has been shown to fragment large protein complexes. Additionally, there is recent evidence to show that IRMPD can help to decluster protein complexes, which should improve the ability to obtain more accurate molecular weight information. Studies of the utility of using IRMPD to fragment and decluster protein complexes will continue. A second project is directed at combining a differential mobility analyzer (DMA) with both QqTOF and triple quadrupole mass spectrometers. Working in collaboration with Yale University, we have developed an efficient interface between the DMA and the MS, and have worked to demonstrate the improved signal-to-noise in real analytical scenarios, including LC/MS/MS analyses of biological samples such as urine extracts. The Yale DMA, with a resolution of >50, is able to separate isomers in many situations. |
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Dr. Wilson received his doctorate from the University of Western Ontario in 2006. His doctoral work under Dr. Lars Konermann centered on the introduction of new Mass Spectrometry and Microfluidics-based technologies for the investigation of rapid dynamic processes in proteins. Dr. Wilson held the top level National Science and Engineering Research Council (NSERC) award, the Canada Graduate Scholarship, throughout his graduate career. He then took up an NSERC post-doctoral fellowship for tenure in the Dobson group at Cambridge . His post-doctoral work on amyloidogenic proteins, including Transtherytin and S. Solfataricus Acylphosphatase extended his expertise to biological NMR, with a focus on biophysical methods. Dr. Wilson has published articles in top ranked international journals including Analytical Chemistry, Biochemistry and the Biophysical Journal. He has also co-authored three book chapters in Protein Structures (Nova Science), Comprehensive Analytical Chemistry (Elsevier) and The Encyclopedia of Mass Spectrometry (Elsevier). His technology for measuring rapid solution phase dynamic processes by Mass Spectrometry was awarded a U.S. Patent in 2005 (#6,870,154). Dr. Wilson’s research at York combines his unique Mass Spectrometry approach with biophysical NMR to study enzyme kinetics and protein dynamics with the aim of paramaterizing models for rational drug design. |
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