We hypothesize that skin microbiota (bacteria, fungi, viruses, phage, archae) plays a significant role in common dermatological conditions, such as atopic dermatitis (eczema). There are two classical explanations for the role microbes play in skin disease: (1) a specific microbe colonizes the skin to disrupt the balance of commensal microflora, or (2) microbes release toxic substances or invade cells to induce an inflammatory response directly. Since culture-dependent skin sampling methods are incomplete, biased assessments of microbial diversity, we propose to use genomic methods to sample skin microflora and shed light on the above conjectures. A cultivation-independent genomic approach directly sequences the microbial DNA, enabling us to imply microbial community membership, structure and diversity. Our initial study of skin bacteria will analyze the bacterial 16s rRNA gene, which contains highly conserved regions, allowing for amplification with specific primers, that flank highly variable regions. These sequences suggest the identity of the species being sampled and enable us to infer phylogenetic relationships. This work has implications for psoriasis and atopic dermatitis (eczema), with long term significance for asthma and hay fever.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG000180-08
Application #
7734877
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2008
Total Cost
$1,107,155
Indirect Cost
Name
National Human Genome Research Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Choi, Yeon Sook; Cheng, Jun; Segre, Julie et al. (2008) Generation and analysis of Elf5-LacZ mouse: unique and dynamic expression of Elf5 (ESE-2) in the inner root sheath of cycling hair follicles. Histochem Cell Biol 129:85-94
Grice, Elizabeth A; Kong, Heidi H; Renaud, Gabriel et al. (2008) A diversity profile of the human skin microbiota. Genome Res 18:1043-50
de Guzman Strong, Cristina; Segre, Julia A (2008) Navigating the genome. J Cell Sci 121:921-3
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List, Karin; Currie, Brooke; Scharschmidt, Tiffany C et al. (2007) Autosomal ichthyosis with hypotrichosis syndrome displays low matriptase proteolytic activity and is phenocopied in ST14 hypomorphic mice. J Biol Chem 282:36714-23
Teng, Andy; Nair, Mahalakshmi; Wells, Julie et al. (2007) Strain-dependent perinatal lethality of Ovol1-deficient mice and identification of Ovol2 as a downstream target of Ovol1 in skin epidermis. Biochim Biophys Acta 1772:89-95
Feinberg, Mark W; Wara, Akm Khyrul; Cao, Zhuoxiao et al. (2007) The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. EMBO J 26:4138-48
Segre, Julia A (2006) Epidermal barrier formation and recovery in skin disorders. J Clin Invest 116:1150-8
Djalilian, Ali R; McGaughey, David; Patel, Satyakam et al. (2006) Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response. J Clin Invest 116:1243-53
Segre, Julia A (2006) Epidermal differentiation complex yields a secret: mutations in the cornification protein filaggrin underlie ichthyosis vulgaris. J Invest Dermatol 126:1202-4

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