Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Post COVID .

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Deep Proteome and Metabolome Profiling

Study AIM

Collaborate with OMF CRCs in Uppsala and Melbourne to establish a global perspective.

Decode the molecular mechanisms underlying ME/CFS and contributing to specific symptoms with a particular emphasis of post-exertional malaise (PEM) through: 

  • Deep phenotyping of ME patients 
  • Global proteomic plasma profiling of ME patients
  • Global metabolomics plasma profiling of ME patients
LEAD INVESTIGATORS
    • Alain Moreau, PhD
    • Jonas Bergquist, MD, PhD
    • Chris Armstrong, PhD
    • Neil McGregor, BDS, MDSc, PhD
Updates and Potential
  • 162 samples were received and pre-treated, and cleanup steps are complete.
  • Samples distributed to both Uppsala and Melbourne centers.
  • Plan to run full-scale proteomics – targeting end of spring/early summer 2022.                
STUDY HYPOTHESIS AND DESCRIPTION

By leveraging our expertise across Open Medicine Foundation ecosystem and through a unique partnership between three OMF Collaborative ME/CFS Research Centers (Melbourne, Montreal and Uppsala), our research team will examine the connections between molecules circulating in the blood and ME. 

This project will provide a more comprehensive understanding as to why some ME patients exhibit different symptoms and how post-exertional malaise exacerbated many symptoms. Identifying specific biomarkers will aid in the development of risk prediction of complications associated with ME, early prevention and better treatments to alleviate the most severe symptoms, which can lead eventually to new therapeutic approaches to cure ME.

No single-omic approach can completely elucidate the multitude of alterations taking place in ME. The DOMINO-ME project will couple a deep phenotyping characterization of ME patients to unbiased discovery strategies by combining global proteomic and metabolomics plasma samples profiling to uncover ME pathogenesis.

Proteomics
The large-scale study of proteins, which are large, complex molecules that are required for structure, function, and regulation of the human body's tissues and organs.
Microvesicles and viral sequencing
Microvesicles are a type of extracellular vesicle that is released from the cell membrane. Vesicles are small, fluid-filled sacs or vacuoles within the body. Sequencing is a technique used to determine the exact sequence of bases (A, C, G, and T) in a DNA (or viral) molecule.
NMR Metabolomics
NMR (Nuclear Magnetic Resonance) is an instrument/tool used to perform metabolic studies, metabolic profiling, and metabolomics in biofluids and tissues for more than 40 years using magnetic fields. There is a very close connection between metabolic measurements and NMR. This connection has flourished because of NMR’s many unique strengths for characterizing complex mixtures’ chemical composition.
Autoantibodies
Antibodies that react with self-molecules and that occur in healthy individuals and are referred to as natural antibodies or autoantibodies.
Extracellular DNA for viral reactivation and Mitochondrial DNA
exDNA (extracellular DNA), exDNA is often secreted actively and is used to perform several tasks, thereby offering an attractive target or tool for biotechnological, medical, environmental, and general microbiological applications. Viruses are intracellular parasites that rely to a significant extent on the host cell for replication. Viral reactivation occurs when an active replication of the viral genome results in a lytic (degradation of the cell) infection characterized by the release of new progeny (descendant) virus particles.
Immune cell profiling
The immune system has many important regulatory roles in disease development and progression. Given the emergence of effective immune therapies, reliable predictors of response are needed. Immune cell profiling determines response by evaluating immune cell populations from treated and untreated samples. For our purposes, we will evaluate the white blood cell response to the viral infection using a process called “Cytof.”
Leukocyte Genomics
A leukocyte is a colorless cell circulating in the blood and body fluids and is involved in counteracting foreign substances and disease. A genome is all genetic material of an organism. Genomics is a biology field focusing on the structure, function, evolution, mapping, and editing of genomes. Therefore, leukocyte genomics is the study of all genetic material of leukocytes.
Metabolomics
Metabolomics is a way to study metabolism – that is, through measuring amounts of the metabolites (small molecules) produced by our bodies as we convert food into energy and other molecules that our cells need to survive. Metabolomics technology is ‘large-scale,’ meaning that several thousand metabolites can be measured from a single sample of e.g., blood or urine.
Micro RNA
Cells use Micro RNA to control whether a particular gene is making too much, too little or the normal amount of its protein at a particular time.