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Publications of the Week

Dynamic Molecular Changes During the First Week of Human Life Follow a Robust Developmental Trajectory

By March 28, 2019No Comments

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This week we profile a recent publication in Nature Communications from an international research team
including Dr. Amy Lee (pictured) at UBC and Casey Shannon at PROOF Centre of Excellence.

Can you provide a brief overview of your lab’s current research focus?

Infection is the most common cause of death in early life, especially for newborns. Our pilot study was designed to understand the molecular changes that occur during the first week of life, as part of the National Institutes of Health (NIH)/National Institute of Allergy & Infectious Diseases (NIAID)-funded Human Immunology Project Consortium (HIPC) study on the Expanded Program on Immunization Consortium (EPIC). This is a large international study including partners at UBC, Boston Children’s Hospital, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Papua New Guinea Institute of Medical Research, University of Western Australia, Institute for Medical Immunology in Belgium, Telethon Kids Institute in Australia, and others.

Amy Lee is currently a research associate in the Hancock Lab in the Department of Microbiology & Immunology at the University of British Columbia. The fundamental interest of the Hancock laboratory is in designing new therapeutic strategies to treat infections in the light of increasing antibiotic resistance coupled with a dearth of new antibiotic discovery. We are particularly interested in understanding host responses to pathogens and inflammatory diseases using systems immunology approaches.

Casey Shannon is a computational biologist and data scientist at the PROOF Centre of Excellence, a not-for-profit organization hosted by Providence Healthcare and the University of British Columbia. PROOF leverages modern high-throughput molecular profiling technologies (transcriptomics, proteomics, metabolomics, etc.) to develop biomarker tests to better predict, diagnose, manage and treat a range of diseases and indications.

What is the significance of the findings in this publication?

One of the major challenges associated with studying neonatal immune development is the amount of blood that can safely be obtained. Our group developed a robust set of standard operating procedures that allows us to obtain transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1 ml (<1/4 teaspoon) of blood. This pilot work, the most comprehensive systems biology study yet performed during the first week of human life, identified profound and robust changes to the newborn immune system in this short time frame.

Applying state-of-the-art multi-omic integration techniques, we were able to demonstrate that these profound changes occur in a coordinated manner across multiple molecular compartments (transcripts, proteins, metabolites). In contrast to the relatively steady-state biology observed in healthy adults, the first week of human life is characterized by a highly dynamic molecular and cellular development, especially in the interferon and complement pathways, as well as neutrophil- associated signalling. Importantly, we observed similar trends across two independent cohorts of babies, from the Gambia and the Papua New Guinea.

What are the next steps for this research?

Our next steps are to apply the methods developed in this pilot work to better understand newborn responses to the hepatitis B and Bacillus Calmette–Guérin vaccines. Our primary goal will be to identify vaccine-induced molecular patterns (“signatures”) that can predict vaccine-mediated protection to help us develop and optimize vaccines against early life infections.

This work was funded by:

Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health as part of the Human Immunology Project consortium under 5U19AI118608-02.

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