Roujeinikova Lab research

Collaborations | Student research projects | Publications

About Associate Professor Anna Roujeinikova

Anna Roujeinikova received her training in Natural Sciences (BSc, MSc) at the Moscow Institute of Physics and Technology and obtained her PhD in Structural Biology at the University of Sheffield (UK). She developed her research programme in the laboratories of the Institute for Cancer Studies (Sheffield, UK), Leicester University (UK) and Manchester University (UK). In 2006, she was awarded a Wellcome Trust Research Career Development Fellowship which supported her work on dissecting the molecular architecture and mode of action of bacterial molecular machines using structural biology techniques. In 2009, she took an academic position as an Associate Professor at Monash University and relocated from the UK to Australia to establish a new structural biology group. She held an ARC Research Fellowship between 2010 and 2014, and currently she works in the Faculty of Medicine, Nursing and Health Sciences as a research and teaching academic. Her group's research focus is the structural biology of bacterial virulence factors, with emphasis on the carcinogenic bacterium Helicobacter pylori.

Our research

Due to rising antibiotic resistance, there is a clear demand for new strategies to fight bacterial infections, strategies that involve new or unconventional targets for drug design. A key to success with this lies in strong basic knowledge of the molecular basis of bacterial virulence and survival.

Our research focuses on three areas:

1. Motility by flagellar motor and its control by chemoreceptors:

   Motility and chemotaxis are well established virulence factors of pathogenic epsilon-proteobacteria, such as Helicobacter pylori and Campylobacter jejuni. We study the mechanism of force generation in H. pylori flagellar motor and the structure and function of the key motility and chemotaxis proteins of H. pylori and C. jejuni.

2. Structure and function of essential bacterial proteins that have not yet experienced selective pressure in the clinical setting:

   The H. pylori eradication rates achieved with the standard therapy have been declining and now fail in approximately 20%-30% of the patients, mainly due to antibiotic resistance. We investigate structure and function of the essential H. pylori proteins that have not yet experienced selective pressure in the clinical setting. The structural insights gained through this work can provide strategies for rational design of novel therapeutics.

3. Interaction of secreted bacterial virulence factors with host cells.

Development of disease (including cancer and irritable bowel disease) in individuals infected with pathogenic epsilon-proteobacteria is facilitated by chronic inflammation caused by the action of the bacterial secreted proteins on the host cells. We investigate the structural basis of the recognition of such proteins by the host’s immune system.

Current projects

1. Architecture of high-torque bacterial flagellar motor specialised for locomotion in viscous liquids (in collaboration with Karen Ottemann (UCSC, USA) and Jun Liu (Yale, USA).

The bacterial flagellar motor is a membrane-embedded molecular machine that rotates filaments, providing a propulsive force for bacteria to swim toward nutrients, optimal temperatures, or other factors that favour survival. Motility by flagellar motor is essential for the survival, chemotaxis and virulence of many pathogenic bacteria. Our model system, the carcinogenic bacterium Helicobacter pylori, uses its polar flagella to drill into the mucus layer of the stomach and move towards the epithelial surface, where it colonizes. Its flagellar motor evolved to drive locomotion in viscous fluids. The striking feature of this motor, revealed by cryo-tomography, is a protein cage that stabilises the wider power-generating ring to sustain the larger turning force. We aim to unravel the make-up of this cage and to understand the structural basis for its ability to recruit force-generating units.

2. Laws of attraction and repulsion: how do bacteria read environmental cues? (In collaboration with Karen Ottemann (UCSC, USA), Ray Norton (Monash, Brian Smith (La Trobe), Igor Zhulin (Ohio State Univ., USA))

Many bacteria are motile. Chemotaxis, mediated by chemoreceptors, plays an important role in bacterial survival and virulence. We investigate what ligands such receptors recognize and why some molecules are attractants and some – repellents, how binding to the receptor leads to signalling, how mutations in the sensor domain affect ligand specificity and, building on this, how bacterial chemoreceptors can be redesigned to recognise and respond to non-native ligands for innovative applications in biotechnology and bioengineering.

3. New targets for the old drugs: exploring the antimicrobial potential of carbonic anhydrase inhibitors (in collaboration with Dr Terry Kowk-Schulein & Professor C. Supuran (Univ. of Florence))

H. pylori has a unique ability to withstand high acidity of the stomach by buffering its periplasm at pH 6, through the action of urease and carbonic anhydrase (CA). We have determined the first crystal structure of this enzyme in complex with inhibitors that have been used clinically for a different purpose, i.e. as antiglaucoma or antiulcer drugs. We evaluate the potential of H. pylori CA as a novel target for treatment against H. pylori by means of the analysis of structure-activity relationships, isolation of mutants with spontaneous resistance and genomic investigation of the resistance mechanisms.

Visit Associate Professor Roujeinikova's Monash research profile to see a full listing of current projects.

Techniques/expertise

Structural biology underpins our research. We use in vitro molecular biophysics methods to investigate structure and dynamics of biomolecules and based on our findings, formulate hypotheses about molecular mechanisms which we then test in vivo through collaborations using a variety of genetics and cell biology methods.

Collaborations

We collaborate with many scientists and research organisations around the world. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

Student research projects

The Song Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.