Molecular profiling of blood for several purposes, 1) To identify prostate cancer biomarkers, 2) to identify commonalities between asthma and mood disorders, and 3) to identify mRNAs that may be involved in psychobiotic changes to behaviour. / Every cell of the body has the opportunity to secrete molecules into the blood.
These molecules: proteins, RNAs, and DNAs, can be secreted freely, or within
extracellular vesicles (EV). The complement of specific molecules secreted by cells can
vary in accordance with changes to their immediate environment, such as disease in a
particular organ. Cells of the immune system which circulate in the blood may also
change the rates at which they produce these molecules in response to a disease or
unusual event occurring somewhere within the body. The full complement of proteins,
RNAs, or DNAs from all sources within the blood can therefore be measured to garner
information about disease states and communication between every tissue of the body. In
this body of work, we leveraged this to address three separate challenges within medical
science. First, we utilized blood as a source of biomarkers for disease and disease
severity; isolating EVs from the blood of prostate cancer patients and healthy subjects
and characterized their proteins with mass spectrometry to identify potential biomarkers
for prostate cancer and its stages. Next, we explored the ability of blood to identify
commonalities between distinct but often comorbid diseases; here we utilized publicly
available datasets to identify transcripts or gene sets potentially facilitating the
relationship between PTSD, MDD, and asthma. Finally, we utilized differential gene and
gene sets expression to gain mechanistic insight into microbiota-gut-brain axis;
investigating the hippocampus and blood of mice fed one of two psychobiotic bacteria:
Lactobacillus rhamnosus JB1, Lactobacillus reuteri 6475. The analysis identified several
mRNA expression differences potentially responsible for the mood-altering characteristics of these psychobiotic bacteria. This body of work illustrates the utility of
blood omics data for addressing many problems within medical science, and highlights
the large scale of information stored within the blood. / Thesis / Doctor of Philosophy (Medical Science) / Every cell of the body has the opportunity to secrete molecules into the blood.
These molecules: proteins, ribonucleic acids (RNAs), and deoxyribonucleic acids
(DNAs), can be secreted freely, or within small membrane compartments called
extracellular vesicles (EV). Specific molecules are secreted more or less by cells
depending on changes to their immediate environment, such as disease in a particular
organ. We leveraged this to the benefit of medical science in three separate scenarios: 1)
using the molecular contents of EVs to determine when someone has prostate cancer, and
at what stage; 2) examining RNAs of the blood to determine why so many with asthma
also have depression or PTSD; 3) measuring RNAs in the blood and hippocampus of
mice to better understand how certain bacteria in the gut can alleviate depression. This
work illustrates the utility of blood in tackling many challenging problems within medical
science.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/28178 |
| Date | January 2022 |
| Creators | Haas-Neill, Sandor |
| Contributors | Forsythe, Paul, Medical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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