The goals of the proposed research are to investigate the functional mechanism used by LytTR Regulatory Systems (LRS) to control gene expression and to explore their role in controlling a cell death pathway in Streptococcus mutans. LRS are a novel class of signal transduction system that consists of a LytTR family transcription regulator and putative membrane protein inhibitor that antagonizes the function of this regulator. The goals of this project will be achieved in two aims by: 1) determining the inhibitory control mechanism employed by two subtypes of LRS and 2) determining the hierarchical transcription control mechanism in the LRS cell death pathway. 1) To determine how LRS membrane proteins function as inhibitors of their cognate transcription regulator proteins, we will examine variety of potential posttranslational inhibitory control mechanisms and map the key residues in LRS proteins responsible for mediating the inhibition. Protein-protein interaction studies will determine whether LRS membrane proteins exert their function directly. 2) To determine how concurrent activation of the HdrRM and BrsRM LRS triggers a cell death pathway, we will test key aspects of a positive feedback cross-regulation model between LRS. Promoter binding studies will be correlated with transcriptional output responses.

Public Health Relevance

Dental caries is one of the most common infectious diseases in humans and is largely correlated with the overgrowth of Streptococcus mutans. These studies aim to reduce the caries burden by examining a novel gene regulatory system that may be exploitable for inhibiting the growth of S. mutans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21DE023850-02
Application #
8914891
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2014-04-09
Project End
2016-03-31
Budget Start
2014-08-18
Budget End
2015-03-31
Support Year
2
Fiscal Year
2014
Total Cost
$167,996
Indirect Cost
$53,880
Name
Oregon Health and Science University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239