Our long-term goal of this exploratory research proposal is to determine how chromosome conformation and subnuclear position affect the host response to viruses. Significance and role of large-scale nuclear processes of folding and juxtaposition of chromosomal fibers during innate immune response to viruses remain relatively unknown. However, these processes represent unexplored epigenetic targets for modulating the innate immune system for potential therapies. To understand these nuclear processes involved in anti-viral response in human cells, we will characterize the molecular mechanisms that modulate chromosomal conformation and subnuclear location of the type I interferon locus in the genome of diploid fibroblasts and lymphoblasts during viral infection. A better understanding of the regulatory mechanisms involved in the production of type I interferons is fundamental to the development of therapeutic strategies for treating viral infections and inflammatory diseases such as autoimmunity.

Public Health Relevance

The type I interferons are critical component of the innate immune response to microbial pathogens, and they coordinate integration of innate and adaptive immune responses. Our project aims to uncover epigenetic mechanisms involving chromosome folding that mediate dynamic and precise activation of type I interferon locus in human cells. These studies will yield potential targets that can be modulated for anti-viral therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI107067-01
Application #
8564095
Study Section
Special Emphasis Panel (ZRG1-IMM-M (08))
Program Officer
Leitner, Wolfgang W
Project Start
2013-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$195,540
Indirect Cost
$78,040
Name
Yale University
Department
Genetics
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Kim, Lark Kyun; Esplugues, Enric; Zorca, Cornelia E et al. (2014) Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells. Mol Cell 54:56-66
Banerjee, A Raja; Kim, Yoon Jung; Kim, Tae Hoon (2014) A novel virus-inducible enhancer of the interferon-? gene with tightly linked promoter and enhancer activities. Nucleic Acids Res 42:12537-54