Recognized these phages as foreign, cleaving their DNA and restricting their This occurred because the host cell enzymes Phages with unmodified DNA, on the other hand, were Previous exposure somehow modified the phage DNA in a way that protected itįrom restriction. Same bacterial strain could successfully infect new host cells, and that the That only those bacteriophages that had previously been in contact with the Genetic defense mechanism (Arber & Linn, 1969). Themselves against foreign DNA through some sort of enzymatically catalyzed Arber wanted to knowĪrber proposed that bacterial cells (in this case, E. Grew poorly were said to be "restricted" by their host. Strain and growing poorly in others (Luria & Human, 1952). Host specific, with each phage surviving and flourishing only in one host bacterial Researchers Salvador Luria and Mary Human had shown that various phages were (also known at the time as host-controlled modification of bacteriophages).īacteriophages are viral particles that invade bacteria and replicate their ownĭNA independently of the bacterial chromosomal DNA. Swiss microbiologist Werner Arber was one of the recipients of theġ978 Nobel Prize in Physiology or Medicine, an award he earned for hisĭiscovery (with Stuart Linn) of restriction enzymes, otherwise known by hisĭaughter Sylvia as "servants with scissors." Arber discovered restrictionĮnzymes while studying a phenomenon known as host-controlled restriction of bacteriophages Sylvia (10 years old), daughter of Werner Arber (as quoted in Konforti, 2000) If a foreign king invades a bacterium, this servant can cut him in small fragments, but he does not do any harm to his own king. My father has discovered a servant who serves as a pair of scissors. My father calls the king DNA, and the servants enzymes. These are thick and short, almost like balls. These colonies remind me of a city with many inhabitants. These plates contain colonies of bacteria. Specifically, we currently work on (1) mitochondrial dynamics and genome instability, (2) arginine and tumor progression and (3) autophagy and drug resistance.When I come to the laboratory of my father, I usually see some plates lying on the tables. Ann’s team is to decipher the signaling transduction pathways and molecular mechanisms underlying adaptive response to metabolic stress. Their results define a mechanism of mitochondrial dynamics regulation that operates in cancer cells under metabolic stress to help preserve their survival, with potential therapeutic implications. Very recently, they found that metabolic stress by restriction of arginine or glucose or inhibition of fatty acid oxidation leads to KAP1 Ser473 phosphorylation to regulate mitochondrial fusion and fission. Their data suggest that arginine depletion results in a decrease of mitochondrial inner membrane and matrix proteins that impairs mitochondrial oxidative phosphorylation (OxPhos) and respiratory function, so-called metabolic stress. While it has long been recognized that some cancer cells are resistant to apoptosis, they discovered an alternative pathway to induce cell death that overcomes resistance to traditional apoptosis associated with cancer. Unlike apoptosis, a cell-death process in which DNA is damaged within the cell nucleus, in chromatin autophagy the nucleus is fragmented and its pieces shuttled off to the lysosome (an organelle within the cell membrane) where the fragments are degraded. Their results describe how arginine starvation specifically kills tumor cells by a novel mechanism involving mitochondria dysfunction, generation of reactive oxygen species, nuclear DNA leakage and chromatophagy, where leaked DNA is captured and “eaten” by giant autophagosomes. His research team focuses on therapeutic implication of ASS1 (argininosuccinate synthetase 1) in breast cancer biology, and we made several novel discoveries by providing a mechanistic link between ASS1 deficiency, arginine deprivation and lethal chromatin autophagy.įurthermore, they identify that arginine deprivation as a new potential breast and prostate cancer therapy that targets a subtype of these cancers that has low ASS1 expression. David Ann, Ph.D., is interested in the role of post-translational modifications including phosphorylation, acetylation, sumoylation, O-glycosylation and ubiquitination in human cancers, with a particular focus on oncogenesis, metastasis and cancer metabolism.
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