Excerpt from National Institute of Neurological and Communicative Disorders and Stroke Annual Report, Vol. 2: July 1, 1975 Through June 30, 1976

The Laboratory has investigated cellular mechanisms controlling differentiation, cellular effects of lipophilic acids and their reversibility, and viral autointerference and persistence. All investigations employed micro - organisms or mammalian cell cultures assuring the availability of large numbers of identical and often synchronized cells and allowing the biochemical investigation of cell or virus components at different times of development. 1) The investigation of differentiation has so far been limited to bacilli in which sporulation occurs almost synchronously and for which many auxo trophic and cacogenic mutants are available that have been analyzed biochem ically and genetically. It was demonstrated that differentiation is not triggered irreversibly by the change of a single macromolecular species, but it comes about by a series of cellular changes each of which renders the reversion to vegetative growth more difficult., In bacilli, the complete engulfment of the prespore cell compartment by a double membrane is responsible for the ultimate commitment to differentiation. Within this new cell compartment, into which compounds can no longer be actively transported, the synthesis of new protein molecules is possible, as has been shown for a spore-specific glucose dehydrogenase which is drastically different from the glucose dehydrogenase of vegetative cells. Manganese ions are required for sporulation because they are needed as co-factor of phosphoglycerate phosphomutase, an enzyme of the glycolytic pathway 2) Lipophilic acids, which include preservatives, antiseptics, and compounds known to cause brain damage or teratogenic effects, inhibit the growth of both bacterial and mammalian cell cultures with about the same potency.

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