Exposomics applies metabolomics methods and technologies to the comprehensive
analysis of all low molecular weight molecules (< 1.5 kDa) in complex biological
samples to characterize the interaction between cellular metabolism and exogenous
lifestyle exposures that determine health and quality of life. To fully access the
diverse classes of biological molecules related to an individual’s metabolic profile,
metabolomics frequently requires the use of complementary analytical platforms,
and employs targeted and untargeted molecular profiling strategies to identify
biomarkers that are clinically relevant to an individual’s health status. Chapter 2
describes a quinoline-based boronic acid biosensor for N-acetylneuraminic acid that
undergoes a striking binding enhancement under strongly acidic conditions. For the
first time, this work allows for direct analysis of acidic sugars with high selectivity
when using UV absorbance or fluorescence detection based on formation of a
highly stable boronate ester complex with metabolites containing an α-hydroxycarboxylate moiety. Chapter 3 describes a targeted analysis of 24 different
organic contaminants using GC-MS that can serve as biomarkers of recent smoke
exposure following search-and-rescue training exercises by firefighters located at
three different sites across the province of Ontario. Importantly, skin and possible
respiratory uptake of various polycyclic aromatic hydrocarbons, methoxyphenols,
and resin acids was confirmed by peak excretion of several wood smoke biomarkers
in urine within 6 h following acute exposure. Chapter 4 applied a cross-platform
metabolomics strategy based on CE-MS and GC-MS in order to identify and
validate dietary biomarkers in matching plasma and urine samples collected from
healthy participants in the pilot Diet and Gene Interaction Study (DIGEST). For the
first time, we demonstrate that a panel of metabolites can serve as reliable
biomarkers following contrasting Prudent and Western diets over 2 weeks of food
provisions, which correlated well with self-reported diet records. This work paves the way for the development of objective biomarkers for accurate assessment of
wood smoke exposures, as well as complex dietary patterns as required for new
advances in occupational health and nutritional epidemiology. / Dissertation / Doctor of Philosophy (PhD) / Exposomics is an emerging multidisciplinary science aimed at deciphering the
complex interactions that impact human health and gene expression, such as
lifestyle choices (i.e., habitual diet) and lifelong environmental exposures. There is
growing interest in identifying biomarkers that can be readily measured for chronic
disease prevention given an alarming global prevalence of obesity and
cardiometabolic disorders, including heart disease, type 2 diabetes and cancer. The
research in this thesis focuses on developing new analytical methods for identifying
and quantifying metabolites that may allow for better assessments of human health,
and has contributed to the development of novel biosensors for the targeted analysis
of N-acetylneuraminic (sialic) acid and related acidic sugars, as well as high
resolution methods for broad spectrum analysis of biotransformed organic
contaminants from smoke exposure by GC-MS, and plasma and urinary metabolites
that differentiate contrasting Prudent and Western diets and correlate well with self-reported
diet records.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/25031 |
| Date | January 2019 |
| Creators | Wellington, Nadine L |
| Contributors | Britz-McKibbin, Philip, Chemistry |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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