Molecular mechanisms of bacterial pathogenesis
The success of a bacterial species depends on its ability to grow and survive in a changing and potentially hostile environment. This requires adaptation at both the single cell and population level. We are particularly interested in understanding how behavior of bacterial populations is underpinned by phenotypic heterogeneity. We furthermore apply our expertise to developing and understanding mechanisms of action of novel antimicrobial therapies. We combine molecular biology and genetic approaches with genomics, immunology and modeling, and collaborate with physicists, mathematicians, biochemists, and clinical researchers internal and external to the University as needed to progress our science. To illustrate these research interests of the MvdW lab, some key research questions and associated research projects in the MvdW lab are outlined below.
An aspect of bacterial populations that is only beginning to be fully appreciated is the heterogeneity of single cells in clonal populations. This heterogeneity raises a multitude of questions of broad significance. How does this heterogeneity arise, which processes are affected by this, and what is the overall effect on the success of the population? Our aim is to shed light on the contribution of population heterogeneity to the strategies bacteria use to survive, prosper, and evolve.
Altering antigenicity is a common bacterial virulence strategy, and this often is a heterogenous trait. We are examining this in Enterobacteriaceae. We have identified Salmonella genes that alter this pathogen’s antigenicity, specifically on carbohydrate surface molecules (the LPS), and have shown that expression phase varies, resulting in population heterogeneity. Our work has elucidated mechanisms of bacterial epigenetic regulation by DNA methylation, which may be applied to synthetic biology and is giving insight into phenotypes of natural pathogen populations. We are studying the proteins that mediate these cell surface changes, and are addressing how these modifications and the heterogeneity impact the interactions of the pathogen with the environment (host or otherwise). This work also is carried out in context of several collaborations. This line of research is in part basic science, and in part aims to provide knowledge that may inform vaccine development strategies and diagnostics, provide insights into pathogen evolution, and may lead to the identification of novel anti-virulence strategies.
Weblogo defining sequences that contribute to epigenetic phase variation of O-antigen modification in Salmonella.
Bacterial infections remain a significant health concern, and are caused by populations of bacteria that have to survive and grow in competitive environments and complex environments. In an interdisciplinary collaboration we are examining how individual cells and toxins affect cell-cell interactions and community development. Our experimental approaches include those facilitated by equipment and expertise from the Imaging and Cytometry labs in the University’s Technology Facility.
The lab’s microbiology knowledge and expertise supports a range of research activities across the University towards developing novel diagnostic approaches, identifying antimicrobial targets and colleagues aiming to apply their specialized knowledge to support development of novel antimicrobial therapies. We work with the York Plasma Institute integrates our microbial knowledge and approaches with the knowledge approaches and expertise on analysis and control of biomedical low temperature plasmas in the YPI. This plasma is the “4th state of matter” and consists of ionized gas, which can deliver a host of toxic compounds to a sample, and has bactericidal activity. However, much remains to be understood from both the plasma physics point of view (remit of YPI) and the biological effects. Our combined efforts aim to support further translation of basic science insights into novel antimicrobial therapies suitable for clinical applications.
The bactericidal activity of Low Temperature Atmospheric Pressure Plasma
Further information, including a full publications list, is available by following the link to the PURE database at the top of this page, in the 'publications' tab.
|Ioannis Passaris||Research Associate||The Roles of Contact-Dependent Inhibition in Building Microbial Communities.|
|Caroline Pearson||PhD Student||Biological Role and Structure Function Analyses of O-Antigen Modifying Enzymes in the Bacterial Pathogen (Co-supervisor G Thomas).|
|Sarah Rixham||PhD Student||Modeling Contact-Dependent Inhibition in Bacteria (Co-supervisor AJ Wood).|
|Helen Davies||PhD Student||
Developing Low Temperature Plasma as a therapy for chronic wound infections. (Main Supervisor Dr. D O’Connell, Physics).
|Jennifer Ferguson||PhD Student||Understanding bacteria stress responses utilizing Raman spectroscopy (Main Supervisor Dr. Y Hancock, Physics).|
I give lectures for Hull York Medical Students and for students in the Biosciences Programmes. I adhere to research led teaching, focusing on introducing concepts both classical and new, disseminating factual knowledge, and providing insight and background to research papers/experiments. The lectures provide overall support for learning. I teach microbiology with topics ranging from basic science to pathogenesis, mainly relating to bacteria. Lectures are tailored to the group I am speaking to and context I am teaching in.
Small group teaching, as in tutorials (Biosciences) or SSIPs (HYMS), allow students to explore scientific topics of their own choosing -within the tutorial remit of “bacteria”, where topics may still range from bacterial pathogenesis to industrial applications, to antimicrobial resistance. Students’ participation is key and their interests help shape the direction of the sessions. We use the sessions as a platform to discuss science and scientific processes, practice critical thinking, study cutting edge research and novel findings, and explore how science works. Broader issues like research ethics, what science graduates can offer society or how much research costs have also been explored.
Research projects for intercalating, undergraduate and Masters students are aligned with the research activities that are ongoing in the lab at the time. I offer primarily lab-based projects, frequently molecular microbiology oriented, but image analysis or other computational projects may be available. Please see the research tab for an overview of current research activities.
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