Molecular biology of Gram-positive bacteria.

Vision, mission and objectives.

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

The vision is to fully understand the molecular mechanisms underlying life and adaptation of our model bacteria to changing environments.

Our mission is to perform top science using advanced genetics, genomics and single cell analytical tools to address fundamental and applied research questions.

Major Topics:

• Bacillus subtilis is studied as a potential cell factory for enzyme and vaccine production as well as for gaining basic insights in differentiation processes, like sporulation and competence development.
• Lactococcus lactis is investigated as model system for various biotechnological applications, and for basic research on gene regulation. Recently, single cell analyses and ncRNAs work has been implemented.
• The human pathogen Streptococcus pneumonia is studied with respect to pathogenesis and virulence.
• Bacilli from soil are studied for plant biocontrol purposes and antimicrobial properties

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 study the very relevant phenotypic heterogeneity that is present in bacterial cultures. We 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, while also natural antimicrobials are being studied for food and environmental application. Pharmaceutical characterization of promising novel antibiotics is undertaken and expanded via appropriate collaborations. Fundamental insights are being exploited for biotechnological as well as for medical applications. A more recent activity is the study of plant-microbe interactions, mostly involving a wide variety of environmental Bacillus strains (over 400 strains have been isolated). These are studied for biocontrol purposes, with a keen interest in endophytic and rhizospheric behavior and their antimicrobial potential. Kuipers has been the major coordinator and supervisor of iGEM (international Genetically Engineered Machine competition) teams at the University of Groningen since 2007. In 2012 the Food Warden team won the overall World Championship of iGEM.

Research areas and subprogrammes.

Research in the Molecular Genetics group consists of four major research themes coupled to application and societal relevance (Fig. 1):

Antimicobials (Kuipers).
Multidrug resistance is an increasing problem in our society, calling 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. Various other modified peptides are developed and characterized while also natral antimicrobials are being studied foor food and environmental applications. Kuipers is Director of the newly established Centre for Sustainable Antimicrobials (CeSAM) in Groningen and is Board member of the Netherlands Antimicrobial Discovery Platform.

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), as well as studies on ncRNAs, in combination with in-house bioinformatics (Dr. de Jong) are used to unravel the principles behind these responses. A very exciting future direction that will be pursued is single cell genomics. Moreover, metagenomics approaches are taken to study plant- and animal microbiota.

Differentiation & Phenotypic heterogeneity (Kuipers, 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 the phenotype in our model organisms is a main theme in our group in which we employ the latest advances in synthetic biology, fluorescence microscopy, microfluidics, next generation sequencing and bioinformatics.

Cell biology (Kok, Kuipers).
A cell biological programme concerning B. subtilis and L. lactis has been initiated. New tools from this programme are employed to investigate virulence gene expression at the single-cell level. In collaboration with other groupsl , super-resolution cell biology is being pursued within a number of projects.

Plant biocontrol (Kuipers).
Over 400 soil Bacilli have been isolated, which are now being studied for plant biocontrol purposes (e.g. potato, tomato, grasslands, onion), with a strong effort in studying their antimicrobial potential, as well as sporulation and germination characteristics. Both endophytes and rhizospheric species are studied.

Teaching

Molecular Genetics is heavily involved in teaching activities, both Bachelor and Masters:

• Genetics I
• Genomics and Proteomics
• Medical Genomics and Proteomics
• Microbiology Research
• Molecular Genetics
• Advanced Transcriptomics
• Advanced Genetic Engineering
• Biotechnology Food and Pharma
• Bioinformatics
• Introduction to Biomedical sciences

Prof. Kok is Director of the Science Masters program on Biomeolecular Sciences and Biotechnology. Prof. Kuipers is Member Royal Dutch Academy of Arts and Sciences, and Program Director of the Center for Sustainable AntiMicrobials (CeSAM). In 2011 he was awarded 500,000 euro as Simon Stevin meester by the Dutch Science Council for Technological studies (STW)

Kuipers and Kok are both Thomson-Reuters ISI Highly Cited Researchers