When a bacterial pathogen infects a host, the host defends itself by producing toxic compounds and inducing unfavorable conditions for the bacterium. The bacterium in turn responds to the new environmental cues, often subverting host defenses by utilizing host-derived signals to trigger upregulation of virulence genes. We are focusing on bacterial transcription factors that respond to such host-derived signals to control expression of virulence genes. Understanding mechanisms by which bacterial pathogens change gene expression programs in response to the environmental cues associated with host infection is critical for development of antibacterial agents.
A major focus is on MarR family transcriptional regulators and the mechanism by which the binding of ligands controls their ability to regulate gene expression. For example, we are currently focusing on how such transcription factors alter gene expression programs in response to oxidative stress or changes in pH.
Genomic DNA in both prokaryotes and eukaryotes is compacted to fit into cellular compartments. We are interested in architectural proteins, so named because a primary function is to induce a specific DNA topology and control DNA compaction. Architectural DNA-binding proteins play important roles in controlling processes such as DNA repair and gene expression. In eukaryotes, failure to regulate these processes correctly may lead to mutagenesis, genomic instability, and cancer.
Current goals pertain to the mechanism by which yeast HMO1 stabilizes nucleosomal arrays and the role of HMO1 in DNA repair and regulation of gene activity. Of specific interest is the role of HMO1 in coordinating gene activity in response to signaling by the Target of Rapamycin (TOR) kinase pathway, which is important for regulating cell growth in response to signals such as nutrient limitation and stress.
Deochand, D. K., Meariman, J. K. and Grove, A. pH-dependent regulation of gene expression by Pectobacterium atrosepticum PecS. (2016). ACS Chem. Biol. 11, 2049-2056.
Panday, A. and Grove, A. The high mobility group protein HMO1 functions as a linker histone in yeast. (2016). Epigenetics Chromatin 9:13.
Sivapragasam, S. and Grove, A. Streptomyces coelicolor XdhR is a direct target of (p)ppGpp that controls expression of genes encoding xanthine dehydrogenase to promote purine salvage. (2016). Mol. Microbiol. 100, 701-718.
Panday, A., Xiao, L. and Grove, A. Yeast high mobility group protein HMO1 stabilizes chromatin and is evicted during repair of DNA double strand breaks. (2015). Nucleic Acids Res. 43, 5759-5770.
Sivapragasam, S., Pande, A. and Grove, A. A recommended workflow for DNase I footprinting using a capillary electrophoresis genetic analyzer. (2015). Anal. Biochem. 481, 1-3.
Gupta, A. and Grove, A. Ligand binding pocket bridges DNA-binding and dimerization
domains of the urate-responsive MarR homologue MftR from Burkholderia thailandensis.
(2014). Biochemistry 53, 4368-4380.
Huang, H. and Grove, A. The transcriptional regulator TamR from Streptomyces coelicolor controls a key step in central metabolism during oxidative stress. (2013). Mol. Microbiol. 87, 1151-1166.
Grove, A. Functional evolution of bacterial histone-like HU proteins. (2011). Curr. Issues Mol. Biol. 13, 1-11. Review.
Perera, I. C. and Grove, A. Molecular mechanisms of ligand-mediated attentuation of DNA binding by MarR family transcriptional regulators. (2010). J. Mol. Cell Biol. 2, 243-254. Review.
Xiao, L. and Grove, A. Coordination of ribosomal protein and ribosomal RNA gene expression in response to TOR signaling. (2009). Curr. Genomics 10, 198-205. Review.