Request ID: cfg_rRequest_3057
Status
:
Approved
Project Description
:
The purpose of this request is to studying \u0093human-type\u0094 immune responses to glycan antigens using the humanized mouse system (HIS), which is a mouse strain that has an immune system genetically modified to resemble the human immune system (see Balazs et al (2014) Nature Med. 20(3):296-300).
CFG Member
:
Member
Requester First Name
:
Zhigang
Requester Last Name
:
Wu
Head of Lab First Name
:
Peng
Head of Lab Last Name
:
Wang
Assigned First Name
:
Peng George
Assigned Last Name
:
Wang
Requester Email
:
zwu14@student.gsu.edu
Requester Interest
:
This laboratory involves different aspects of glycoscience - Glycochemistry, Glycobiology, and Glycoanalysis and glycomics
Request Date [yyyy-mm-dd]
:
2014-05-06
Institution
:
Department of Chemistry, Georgia State University
Shipping Address
:
Department of Chemistry,Georgia State University,Natural Science Center Rm433,
50 Decatur St SE,
Atlanta, GA 30303
Tel: 404-413-5607
Comments
:
The purpose of our project is studying human-type immune responses to glycan antigens and could lead to immunization studies of such animals for protective anti-glycan responses as a model of primate and human immunobiology.
CFG Core
:
H
Resource Type
:
MicroArray
Amount Requested
:
Information not entered/not applicable.
Date that your RNA/GBP samples will be sent to the core [yyyy-mm-dd]
:
2014-05-13
Experiment to be conducted
:
The repertoire of anti-glycan antibodies in people and rodents is not well understood but to some degree it reflects prior exposure to pathogens (parasites and microbes) and their unusual glycans. In addition, individual humans and rodents typically lack antibodies to their cognate blood groups, e.g. human ABO(H), Lewis antigens, and CAD/Sda, etc. In this regard a significant development in immunology has been the humanized mice that have recently emerged as a powerful tool for the development of effective and affordable vaccines and therapeutics. The humanized mouse system (HIS) has an immune system genetically modified to resemble the human immune system. Such mice make it possible to explore human immunity to disease, such as susceptibility to HIV-infection (see Balazs et al (2014) Nature Med. 20(3):296-300).
My laboratory is collaborating with the lab of Dr. Richard A. Flavell (Yale), who has made available sera from Mice repopulated with human hematopoietic cells, that he is using to explore human hematopoiesis and immune function in vivo. [Our specific collaborative studies are more related to susceptibility and responses of these animals to microbial infections in terms of their glycan presentations.] These new mice overcome many of the prior problems of humanization due to inappropriate cytokine stimulation; the Flavell lab generated immunodeficient Rag2−/−Il2rg−/− mice in which the genes encoding human M-CSF, human interleukin 3 (IL-3) and GM-CSF, and human thrombopoietin are knocked in to their respective mouse loci. These mice are named MITRG for the encoded proteins M-CSF, IL-3/GM-CSF and TPO in the Rag2−/−Il2rg−/− background. The serum of these humanized mice has not been compared to wild-type mice in the same facility in terms of anti-glycan responses. We acknowledge that prior studies by the CFG have shown that both human and mouse sera contain a variety of antibodies to glycans on both the CFG and the pathogen (now MGM) glycan microarrays. Here we wish to test pooled sera from both the wild-type and MITRG-mice in an exploratory fashion to identify if there are significant differences or similarities in anti-glycan repertoire. We realize this is a fishing expedition, but in discussion with Dr. Flavell, he was astonished to learn about the glycan microarrays and the facts that anti-glycan antibodies are readily measurable in human and rodent sera, and was significantly enthused to provide sera for further testing. We would estimate that only 6 slides are needed [2 control sera and 2 for MITRG-sera and 2 for pooled human sera (normal controls) at multiple concentrations and screening for IgG and IgM].
We have prepared the following samples for analysis:
4 samples of sera from MISTRG mice which is Human immune system (HIS) mice, 1 sample of sera from CD-1 mouse (normal mouse serum, foster mothers in transgenic core) as control, and 1 sample of sera from human as control.
The preliminary information from this screen could provide information as to the value of such humanized mice for studying human-type immune responses to glycan antigens and could lead to immunization studies of such animals for protective anti-glycan responses as a model of primate and human immunobiology.
Within Scope of Consortium
:
Y
If yes, indicate the person responsible for inputing data into core B
:
Peng George Wang
GBP being Addressed
:
Information not entered/not applicable.
Specifc aims being addressed
:
Identify the ligand(s) that mediate GBP binding. Determine how GBP-ligand interactions mediate cell communication. Determine the structures of selected GBPs.