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Mark Bretscher joined the MRC Unit in the Cavendish in 1961 as a research student. Working on the genetic code with Francis Crick, he established the linkage between the growing polypeptide and tRNA and its cleavage during polypeptide termination. After a post-doc with Paul Berg at Stanford (1964-5), he continued to work on polypeptide chain initiation and termination at the LMB. He analysed the structure of the erythrocyte membrane (1971), discovering the topology of its main proteins and its asymmetric bilayer, laying the foundations for present concepts of membrane structure. Shifting to animal cell movement, he proposed (1976/84) that a polarised endocytic cycle is the principal force propelling a cell forward, for which there is now much evidence. More recently he developed methods for generating temperature-sensitive mutations in the amoeba Dictyostelium, discovering the first genes required for cell locomotion. Mark combines an unusual mixture of experimental and theoretical innovation. He proposed models for how ribosomes translocate ('Hybrid Site model', 1968), how asymmetric bilayers form (using 'flippases', 1972) and how cells cap surface antigens and move ('Lipid Flow', 1976). He has never had a formal group, preferring to work on his own with the occasional visitor.
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| My main interest, how cell membranes function, is now focussed on their role in cell movement. Experiment shows that exocytosis occurs at the fronts of several motile mammalian cells, providing the surface needed for cell extension.
I have recently devised new methods for
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isolating conditional mutants in essential genes of the motile Dictyostelium amoeba. Temperature-sensitive mutants in two key membrane recycling genes - NSF and Sec1- have been made. Both lines stop moving at the restrictive temperature and encode the first proteins shown to be required for cell migration.
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