Celebratory Inaugural Lecture of Charles Dorman

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Joly Lecture Theatre

Hamilton Building

Trinity College Dublin

Dublin 2 Dublin

Ireland

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Professor Sylvia Draper, Dean of the Faculty of Engineering, Mathematics and Science requests the pleasure of your company

“Unpredictable”

Celebratory Inagural Lecture by Professor Charles Dorman

Many of the model organisms that have elucidated important principles in microbiology, inhabit environments that are prone to fluctuations in their physical nature and chemical composition. Environmental unpredictability presents the microbial population with the challenge of ensuring that at least some members are prepared for each new set of circumstances as it arises. The solution involves having in the population some members that are either prepared or that can adapt rapidly. Genetic change (mutation) creates physiological diversity, but once the mutation becomes fixed, the organism has moved to a new physiological baseline. A more flexible approach relies on cell-to-cell differences in the expression of copies of the same genes across the population. To understand how this is possible, it is important to appreciate that DNA, metaphorically, contains two types of information: digital-like information in the form of the sequence of bases and analogue-like information in the form of DNA shape. Changes to the base sequence result in mutations whereas changes to DNA shape influence the likelihood, and the degree, to which a given copy of a gene will be expressed in an individual cell. The act of transcription by DNA-dependent RNA polymerase transforms the shape of DNA and this has to be managed and reset by cellular enzymes called topoisomerases and by other DNA binding proteins. Topological variation in DNA also occurs in a programmed way in response to environmental stresses that alter the activities of these enzymes. In this way, the environment influences the presentation of genetic information to the gene expression machinery on a cell-by-cell basis, so that no two members of the population are likely to be expressing the same gene to the same extent at a given time. The environment then selects the cells that happen to be optimally 'fit'. It will be argued that the generation of physiological variety affects the efficiencies of horizontal gene transfer processes (and hence microbial evolution) and helps pathogenic bacteria to evade host defences by allowing the bacterium to experiment with the expression of physiologically 'expensive' gene sets that, if switched on inappropriately, might cause the microbe to be eliminated. The molecular mechanisms that underlie the resulting microbial unpredictability, and the regulatory hierarchies and networks within which they operate, will be described in this lecture.

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Joly Lecture Theatre

Hamilton Building

Trinity College Dublin

Dublin 2 Dublin

Ireland

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