ingest cdrApp 2018-06-13T15:36:56.807Z 51cd2fe2-3fd7-401f-a923-a97bc3db68a2 modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T16:04:13.092Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2018-06-13T16:04:24.766Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2018-06-13T16:04:48.029Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T16:04:48.810Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-16T21:10:43.046Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-18T16:44:59.483Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-22T15:25:53.383Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-28T18:15:06.590Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-12T17:04:59.337Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-22T20:26:29.582Z Lior Vered Author Department of Chemistry College of Arts and Sciences Memory and Bistability in the Pheromone Response Pthway Polarity is the asymmetric organization of cellular structures, and is critical for differentiation, morphogenesis and migration in all eukaryotes. Many mathematical models of polarity rely on the existence of two stable steady states, and which state is observed depends on past conditions. However, bistable regulation of polarity has yet to be proven experimentally. One of the hallmarks of a bistability is hysteresis, a mechanism of memory in which the response of a system depends on its history. To identify hysteresis, we compared the minimum pheromone concentration needed to establish polarity with the minimum concentration needed to maintain polarity. Using a method of live-cell microfluidic microscopy, we determined that the minimum pheromone concentration required to establish polarity is 6 nM. When determining the minimum pheromone concentration required to maintain polarity, we observed that during a multi-step reduction of pheromone concentration most cells continued to hold polarity and cell cycle arrest at concentrations below 6 nM. In fact, a fraction of cells (~30%) held polarity and cell cycle arrest even after pheromone was completely removed. The difference between the minimum pheromone concentration required to establish polarity (~ 6 nM), and the minimum concentration required to maintain polarity (~ 0 nM), suggests that the polarity is bistable. Surprisingly, cells will disassemble polarity rapidly after a one-step reduction in pheromone concentration to 5 nM or less. The finding that the number of steps taken to reduce the pheromone concentration determines whether cells maintain polarity is consistent with a model containing a slow-adjusting negative regulation and a fast-adjusting positive feedback. We confirmed this model by successfully testing two predictions – that whether cells lose polarity after a one-step pheromone reduction and the rate at which polarity disassembly occurs will depend on the initial pheromone concentration. Our studies have shown that pheromone regulated polarity is bistable. We also confirmed a model of slow-adjusting negative regulation and fast-adjusting positive feedback that plays a role in this mechanism of memory. The presence of bistability in pheromone regulated polarity is informative to the study of polarity in other organisms and will inform future mathematical models. Spring 2018 2018 Systematic biology Pharmacology Cellular biology Bistability, Budding Yeast, Hysteresis, Pheromone Response, Polarity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Timothy Elston Thesis advisor Henrik Dohlman Thesis advisor Dorothy Erie Thesis advisor Beverly Errede Thesis advisor Nancy Thompson Thesis advisor text Lior Vered Author Department of Chemistry College of Arts and Sciences Memory and Bistability in the Pheromone Response Pthway Polarity is the asymmetric organization of cellular structures, and is critical for differentiation, morphogenesis and migration in all eukaryotes. Many mathematical models of polarity rely on the existence of two stable steady states, and which state is observed depends on past conditions. However, bistable regulation of polarity has yet to be proven experimentally. One of the hallmarks of a bistability is hysteresis, a mechanism of memory in which the response of a system depends on its history. To identify hysteresis, we compared the minimum pheromone concentration needed to establish polarity with the minimum concentration needed to maintain polarity. Using a method of live-cell microfluidic microscopy, we determined that the minimum pheromone concentration required to establish polarity is 6 nM. When determining the minimum pheromone concentration required to maintain polarity, we observed that during a multi-step reduction of pheromone concentration most cells continued to hold polarity and cell cycle arrest at concentrations below 6 nM. In fact, a fraction of cells (~30%) held polarity and cell cycle arrest even after pheromone was completely removed. The difference between the minimum pheromone concentration required to establish polarity (~ 6 nM), and the minimum concentration required to maintain polarity (~ 0 nM), suggests that the polarity is bistable. Surprisingly, cells will disassemble polarity rapidly after a one-step reduction in pheromone concentration to 5 nM or less. The finding that the number of steps taken to reduce the pheromone concentration determines whether cells maintain polarity is consistent with a model containing a slow-adjusting negative regulation and a fast-adjusting positive feedback. We confirmed this model by successfully testing two predictions – that whether cells lose polarity after a one-step pheromone reduction and the rate at which polarity disassembly occurs will depend on the initial pheromone concentration. Our studies have shown that pheromone regulated polarity is bistable. We also confirmed a model of slow-adjusting negative regulation and fast-adjusting positive feedback that plays a role in this mechanism of memory. The presence of bistability in pheromone regulated polarity is informative to the study of polarity in other organisms and will inform future mathematical models. Spring 2018 2018 Systematic biology Pharmacology Cellular biology Bistability, Budding Yeast, Hysteresis, Pheromone Response, Polarity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Timothy Elston Thesis advisor Henrik Dohlman Thesis advisor Dorothy Erie Thesis advisor Beverly Errede Thesis advisor Nancy Thompson Thesis advisor text Lior Vered Author Department of Chemistry College of Arts and Sciences Memory and Bistability in the Pheromone Response Pthway Polarity is the asymmetric organization of cellular structures, and is critical for differentiation, morphogenesis and migration in all eukaryotes. Many mathematical models of polarity rely on the existence of two stable steady states, and which state is observed depends on past conditions. However, bistable regulation of polarity has yet to be proven experimentally. One of the hallmarks of a bistability is hysteresis, a mechanism of memory in which the response of a system depends on its history. To identify hysteresis, we compared the minimum pheromone concentration needed to establish polarity with the minimum concentration needed to maintain polarity. Using a method of live-cell microfluidic microscopy, we determined that the minimum pheromone concentration required to establish polarity is 6 nM. When determining the minimum pheromone concentration required to maintain polarity, we observed that during a multi-step reduction of pheromone concentration most cells continued to hold polarity and cell cycle arrest at concentrations below 6 nM. In fact, a fraction of cells (~30%) held polarity and cell cycle arrest even after pheromone was completely removed. The difference between the minimum pheromone concentration required to establish polarity (~ 6 nM), and the minimum concentration required to maintain polarity (~ 0 nM), suggests that the polarity is bistable. Surprisingly, cells will disassemble polarity rapidly after a one-step reduction in pheromone concentration to 5 nM or less. The finding that the number of steps taken to reduce the pheromone concentration determines whether cells maintain polarity is consistent with a model containing a slow-adjusting negative regulation and a fast-adjusting positive feedback. We confirmed this model by successfully testing two predictions – that whether cells lose polarity after a one-step pheromone reduction and the rate at which polarity disassembly occurs will depend on the initial pheromone concentration. Our studies have shown that pheromone regulated polarity is bistable. We also confirmed a model of slow-adjusting negative regulation and fast-adjusting positive feedback that plays a role in this mechanism of memory. The presence of bistability in pheromone regulated polarity is informative to the study of polarity in other organisms and will inform future mathematical models. Spring 2018 2018 Systematic biology Pharmacology Cellular biology Bistability, Budding Yeast, Hysteresis, Pheromone Response, Polarity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Timothy Elston Thesis advisor Henrik Dohlman Thesis advisor Dorothy Erie Thesis advisor Beverly Errede Thesis advisor Nancy Thompson Thesis advisor text Lior Vered Author Department of Chemistry College of Arts and Sciences Memory and Bistability in the Pheromone Response Pthway Polarity is the asymmetric organization of cellular structures, and is critical for differentiation, morphogenesis and migration in all eukaryotes. Many mathematical models of polarity rely on the existence of two stable steady states, and which state is observed depends on past conditions. However, bistable regulation of polarity has yet to be proven experimentally. One of the hallmarks of a bistability is hysteresis, a mechanism of memory in which the response of a system depends on its history. To identify hysteresis, we compared the minimum pheromone concentration needed to establish polarity with the minimum concentration needed to maintain polarity. Using a method of live-cell microfluidic microscopy, we determined that the minimum pheromone concentration required to establish polarity is 6 nM. When determining the minimum pheromone concentration required to maintain polarity, we observed that during a multi-step reduction of pheromone concentration most cells continued to hold polarity and cell cycle arrest at concentrations below 6 nM. In fact, a fraction of cells (~30%) held polarity and cell cycle arrest even after pheromone was completely removed. The difference between the minimum pheromone concentration required to establish polarity (~ 6 nM), and the minimum concentration required to maintain polarity (~ 0 nM), suggests that the polarity is bistable. Surprisingly, cells will disassemble polarity rapidly after a one-step reduction in pheromone concentration to 5 nM or less. The finding that the number of steps taken to reduce the pheromone concentration determines whether cells maintain polarity is consistent with a model containing a slow-adjusting negative regulation and a fast-adjusting positive feedback. We confirmed this model by successfully testing two predictions – that whether cells lose polarity after a one-step pheromone reduction and the rate at which polarity disassembly occurs will depend on the initial pheromone concentration. Our studies have shown that pheromone regulated polarity is bistable. We also confirmed a model of slow-adjusting negative regulation and fast-adjusting positive feedback that plays a role in this mechanism of memory. The presence of bistability in pheromone regulated polarity is informative to the study of polarity in other organisms and will inform future mathematical models. Spring 2018 2018 Systematic biology Pharmacology Cellular biology Bistability, Budding Yeast, Hysteresis, Pheromone Response, Polarity eng Doctor of Philosophy Dissertation Chemistry Timothy Elston Thesis advisor Henrik Dohlman Thesis advisor Dorothy Erie Thesis advisor Beverly Errede Thesis advisor Nancy Thompson Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Lior Vered Creator Department of Chemistry College of Arts and Sciences Memory and Bistability in the Pheromone Response Pthway Polarity is the asymmetric organization of cellular structures, and is critical for differentiation, morphogenesis and migration in all eukaryotes. Many mathematical models of polarity rely on the existence of two stable steady states, and which state is observed depends on past conditions. However, bistable regulation of polarity has yet to be proven experimentally. One of the hallmarks of a bistability is hysteresis, a mechanism of memory in which the response of a system depends on its history. To identify hysteresis, we compared the minimum pheromone concentration needed to establish polarity with the minimum concentration needed to maintain polarity. Using a method of live-cell microfluidic microscopy, we determined that the minimum pheromone concentration required to establish polarity is 6 nM. When determining the minimum pheromone concentration required to maintain polarity, we observed that during a multi-step reduction of pheromone concentration most cells continued to hold polarity and cell cycle arrest at concentrations below 6 nM. In fact, a fraction of cells (~30%) held polarity and cell cycle arrest even after pheromone was completely removed. The difference between the minimum pheromone concentration required to establish polarity (~ 6 nM), and the minimum concentration required to maintain polarity (~ 0 nM), suggests that the polarity is bistable. Surprisingly, cells will disassemble polarity rapidly after a one-step reduction in pheromone concentration to 5 nM or less. The finding that the number of steps taken to reduce the pheromone concentration determines whether cells maintain polarity is consistent with a model containing a slow-adjusting negative regulation and a fast-adjusting positive feedback. We confirmed this model by successfully testing two predictions – that whether cells lose polarity after a one-step pheromone reduction and the rate at which polarity disassembly occurs will depend on the initial pheromone concentration. Our studies have shown that pheromone regulated polarity is bistable. We also confirmed a model of slow-adjusting negative regulation and fast-adjusting positive feedback that plays a role in this mechanism of memory. The presence of bistability in pheromone regulated polarity is informative to the study of polarity in other organisms and will inform future mathematical models. Systematic biology Pharmacology Cellular biology Bistability; Budding Yeast; Hysteresis; Pheromone Response; Polarity eng Doctor of Philosophy Dissertation Chemistry Timothy Elston Thesis advisor Henrik Dohlman Thesis advisor Dorothy Erie Thesis advisor Beverly Errede Thesis advisor Nancy Thompson Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution 2018 2018-05 Lior Vered Author Department of Chemistry College of Arts and Sciences Memory and Bistability in the Pheromone Response Pthway Polarity is the asymmetric organization of cellular structures, and is critical for differentiation, morphogenesis and migration in all eukaryotes. Many mathematical models of polarity rely on the existence of two stable steady states, and which state is observed depends on past conditions. However, bistable regulation of polarity has yet to be proven experimentally. One of the hallmarks of a bistability is hysteresis, a mechanism of memory in which the response of a system depends on its history. To identify hysteresis, we compared the minimum pheromone concentration needed to establish polarity with the minimum concentration needed to maintain polarity. Using a method of live-cell microfluidic microscopy, we determined that the minimum pheromone concentration required to establish polarity is 6 nM. When determining the minimum pheromone concentration required to maintain polarity, we observed that during a multi-step reduction of pheromone concentration most cells continued to hold polarity and cell cycle arrest at concentrations below 6 nM. In fact, a fraction of cells (~30%) held polarity and cell cycle arrest even after pheromone was completely removed. The difference between the minimum pheromone concentration required to establish polarity (~ 6 nM), and the minimum concentration required to maintain polarity (~ 0 nM), suggests that the polarity is bistable. Surprisingly, cells will disassemble polarity rapidly after a one-step reduction in pheromone concentration to 5 nM or less. The finding that the number of steps taken to reduce the pheromone concentration determines whether cells maintain polarity is consistent with a model containing a slow-adjusting negative regulation and a fast-adjusting positive feedback. We confirmed this model by successfully testing two predictions – that whether cells lose polarity after a one-step pheromone reduction and the rate at which polarity disassembly occurs will depend on the initial pheromone concentration. Our studies have shown that pheromone regulated polarity is bistable. We also confirmed a model of slow-adjusting negative regulation and fast-adjusting positive feedback that plays a role in this mechanism of memory. The presence of bistability in pheromone regulated polarity is informative to the study of polarity in other organisms and will inform future mathematical models. Spring 2018 2018 Systematic biology Pharmacology Cellular biology Bistability, Budding Yeast, Hysteresis, Pheromone Response, Polarity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Chemistry Timothy Elston Thesis advisor Henrik Dohlman Thesis advisor Dorothy Erie Thesis advisor Beverly Errede Thesis advisor Nancy Thompson Thesis advisor text Lior Vered Creator Department of Chemistry College of Arts and Sciences Polarity is the asymmetric organization of cellular structures, and is critical for differentiation, morphogenesis and migration in all eukaryotes. Many mathematical models of polarity rely on the existence of two stable steady states, and which state is observed depends on past conditions. However, bistable regulation of polarity has yet to be proven experimentally. One of the hallmarks of a bistability is hysteresis, a mechanism of memory in which the response of a system depends on its history. To identify hysteresis, we compared the minimum pheromone concentration needed to establish polarity with the minimum concentration needed to maintain polarity. Using a method of live-cell microfluidic microscopy, we determined that the minimum pheromone concentration required to establish polarity is 6 nM. When determining the minimum pheromone concentration required to maintain polarity, we observed that during a multi-step reduction of pheromone concentration most cells continued to hold polarity and cell cycle arrest at concentrations below 6 nM. In fact, a fraction of cells (~30%) held polarity and cell cycle arrest even after pheromone was completely removed. The difference between the minimum pheromone concentration required to establish polarity (~ 6 nM), and the minimum concentration required to maintain polarity (~ 0 nM), suggests that the polarity is bistable. Surprisingly, cells will disassemble polarity rapidly after a one-step reduction in pheromone concentration to 5 nM or less. The finding that the number of steps taken to reduce the pheromone concentration determines whether cells maintain polarity is consistent with a model containing a slow-adjusting negative regulation and a fast-adjusting positive feedback. We confirmed this model by successfully testing two predictions – that whether cells lose polarity after a one-step pheromone reduction and the rate at which polarity disassembly occurs will depend on the initial pheromone concentration. Our studies have shown that pheromone regulated polarity is bistable. We also confirmed a model of slow-adjusting negative regulation and fast-adjusting positive feedback that plays a role in this mechanism of memory. The presence of bistability in pheromone regulated polarity is informative to the study of polarity in other organisms and will inform future mathematical models. 2018-05 2018 Systematic biology Pharmacology Cellular biology Bistability; Budding Yeast; Hysteresis; Pheromone Response; Polarity eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Timothy Elston Thesis advisor Henrik Dohlman Thesis advisor Dorothy Erie Thesis advisor Beverly Errede Thesis advisor Nancy Thompson Thesis advisor text Vered_unc_0153D_17839.pdf uuid:92a4fffb-062b-4b0d-9b02-dca98f047c75 2020-06-13T00:00:00 2018-05-01T03:34:18Z proquest application/pdf 914451