Research Interests

Major Research Interests: We are interested in the molecular mechanisms of bacterial pathogenesis, focusing on the human pathogen Streptococcus pneumoniae, and are also developing novel tools for molecular near-infra red (NIR) imaging of disease.

Project I: Streptococcus pneumoniae pathogenesis.
We are interested in understanding the signaling processes that enables pathogenic bacteria to thrive in the host and cause disease. Our lab focuses on the Gram-positive pathogen Streptococcus pneumoniae, responsible for 25% of all preventable deaths in children under the age of 5, and the leading cause in the US of community acquired pneumonia-related deaths. Although S. pneumoniae is responsible for a considerable disease burden on society, it first resides as a harmless commensal in the nasopharynx, before disseminating into the host to cause a variety of infections under situations where one’s immune system is compromised. A key component of the success of the pneumococcus is its ability to avoid innate immunity via its polysaccharide capsule, which is its major virulence factor and defines the > 90 capsule-specific serotypes. As the current vaccine is composed only of a subset of these serotypes, it would be beneficial to identify new therapeutics for targeting all pneumococcal serotypes rather than a few. The goal of our research is to understand conserved molecular events that trigger the deadly switch from commensal to pathogenesis. Through this research we have discovered a novel pathway that we think is responsible for this key change in carrier state and involving capsule tissue-specific regulation. Excitingly, it appears this system is conserved in many other Gram-positive pathogens.

Project II: Alternative roles and evolution of two-component signaling.
All life on earth requires a means to detect their continuously changing environment or perish. In the simplest context, organisms generally have sensory receptors for this that when stimulated, respond to activate a precise signaling cascade by chemically altering the amino acids of another ‘downstream’ protein. These chemical altercations are collectively referred to as posttranslational modifications (PTMs) and can take on many forms. Two-component signaling systems are the primary means by which most life on earth senses their external environment. The canonical relay system consists of a sensor histidine kinase phosphorylating a conserved aspartate (Asp) residue on a Receiver (REC) domain. Our lab has discovered that substantial numbers of the critical REC domains are missing the phosphorylatable Asp residue, which has revealed an unexpected potential for diverse signaling inputs. We have named this new class of proteins the “Aspartate-Less Receiver (ALR) domains. This project aims to show that the most widely used signaling domains in nature (REC domains) can be activated by an infinite number of signal inputs rather than just one.

Project III. Phytochromes as tools for molecular imaging and sensing heme.
Phytochromes are classically unique red/far-red light receptors used by plants and bacteria to respond to light in the Near Infra-red (NIR). A number of years ago we and others created fluorescent versions of these proteins that could now significantly impact the field of imaging, as Phytochrome-Based Fluorophores (PBFs) emit at NIR wavelengths that are within the ideal optical window for deep tissue imaging. Our lab is interested in developing new and improved versions of PBFs to enable visualization of molecular events in whole animals without the need for surgical intervention. As PBFs use the heme breakdown product of biliverdin (BV) to enable their unique fluorescence, we have also exploited these unique fluorescent proteins as heme biosensors in pathogenic bacteria, such as the Cystic Fibrosis pathogen Pseudomonas aeruginosa. Using PBFs in this Gram-negative pathogen we have identified novel genes involved in iron/heme metabolism, paving the way for using this biosensor to identify iron/heme components in any biological system, including both prokaryotic and eukaryotic organisms.

Publications

1. Maule AF, Wright DP, Han L, Weiner JJ, Peterson FC, Volkman BF, Silvaggi NR* and Ulijasz AT* The Aspartate-Less Receiver (ALR) domains: Distribution, structure and function. 2015: PLoS Pathog. 11:e1004795.

2. Wright DP and Ulijasz AT* Regulation of transcription by eukaryotic-like serine-threonine kinases in bacteria. 2014: Virulence. 5: 863-885.

3. Cornilescu CC, Cornilescu G, Burgie ES, Markley JL, Ulijasz AT* and Viersta RD*. Dynamic structural changes underpin photoconversion of a blue/green cyanobacteriochrome between its ground and photoactivated states. 2014: J. Biol. Chem. 289: 2552-62.

4. Ulijasz AT* Vierstra RD. Phytochrome structure and photochemistry: Recent advances towards a complete molecular picture. Curr. Opin. Plant Biol. 2011: 14: 498-506.

5. Ulijasz AT1, Cornilescu G1, Cornilescu CC, Zhang J, Rivera M, Markley JL, Vierstra RD*. Structural basis for the photoconversion of a phytochrome to the activated Pfr form. Nature. 2010: 463: 250-4.

6. Glanville, D.G., et al. and Ulijasz, A.T., RitR is an archetype for a novel family of redox sensors in the streptococci that has evolved from two-component response regulators and is required for pneumococcal colonization. PLoS Pathog, 2018. 14(5):e1007052. doi: 10.1371. PMCID: 29750817. 

* Corresponding author(s)
¹ Contributed equally