Molecular biology of Gram-positive bacteria.


Vision, mission and objectives.

The Molecular Genetics group focuses on the molecular biology, physiology, genetics and functional genomics of AT-rich Gram-positive bacteria of industrial and health interest.

Vision: To fully understand the molecular mechanisms underlying life and the adaptation of our model bacteria to changing environments.

Mission: Performing top science using advanced genetics, genomics and single-cell analytical tools to address fundamental and applied research questions.

Objectives: Bacillus subtilis is studied as a potential cell factory for enzyme and vaccine production as well as for gaining basic insights in differentiation processes. Lactococcus lactis is investigated as model system for various biotechnological applications, and is used for basic research on gene regulation. The human pathogen Streptococcus pneumonia is studied with respect to pathogenesis and virulence. A major focus of the group is to not only study cells using averaging culture assays, but also to take single-cell behavior into account and investigate the very relevant phenotypic heterogeneity that is present in bacterial cultures. It is our aim to unravel novel molecular mechanisms leading to phenotypic heterogeneity, which can be a benefit for the whole bacterial culture and the survival of the species. We attempt to explore original avenues to be able to reach highly novel and relevant research results. Moreover, we will continue successful research lines employing functional genomics supported by own bioinformatics expertise. Synthetic biology approaches are taken for the development of novel antimicrobial molecules. Fundamental insights are being exploited for biotechnological as well as for medical applications.

Research areas and subprogrammes.

Research in the Molecular Genetics group consists of four major research themes coupled to two subprogrammes of application and societal relevance

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Antimicobials (Kuipers). The increase in multidrug resistance calls for new classes of antimicrobials. Using a synthetic biology approach, silent lantibiotics from various genetic sources are produced in a plug-and-play expression system. The molecular mechanisms underlying lantibiotic production are being unravelled to improve production.

Functional Genomics (Kok, Kuipers). How bacteria respond to their environment and combat various stresses is an important question in biology. Several ‘omics’ techniques (proteomics, transcriptomics, RNA sequencing, ChIP-chip), in combination with in-house bioinformatics are used to unravel the principles behind these responses. A very exiting future direction that will be pursued is single-cell genomics.

Differentiation & Phenotypic heterogeneity (Kuipers, Veening, Kok). Our group is one of the pioneers in the field of phenotypic heterogeneity i.e., the notion that within a genetically identical population of bacterial cells under identical conditions, a significant cell-to-cell variability in gene expression exists. How noise contributes to phenotype in our model organisms is a main theme in which we employ the latest advances in synthetic biology, fluorescence microscopy, microfluidics, next generation sequencing and bioinformatics.

Cell biology (Veening, Kok). A cell biological program concerning S. pneumoniae and L. lactis has been initiated. New tools from this program are employed to investigate membrane protein insertion and virulence gene expression at the single-cell level. In collaboration with Prof. van Oijen, super-resolution cell biology is being pursued within a number of projects.

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