This article was downloaded by: [Selcuk Universitesi] On: 31 January 2015, At: 03:00 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Bacteriophage Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/kbac20
Life in Science: Björn H Lindqvist a
Björn H Lindqvist a
Department of Molecular Biosciences; University of Oslo; Oslo, Norway Published online: 01 Oct 2013.
To cite this article: Björn H Lindqvist (2013) Life in Science: Björn H Lindqvist, Bacteriophage, 3:4, e26673, DOI: 10.4161/ bact.26673 To link to this article: http://dx.doi.org/10.4161/bact.26673
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Versions of published Taylor & Francis and Routledge Open articles and Taylor & Francis and Routledge Open Select articles posted to institutional or subject repositories or any other third-party website are without warranty from Taylor & Francis of any kind, either expressed or implied, including, but not limited to, warranties of merchantability, fitness for a particular purpose, or non-infringement. Any opinions and views expressed in this article are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor & Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions It is essential that you check the license status of any given Open and Open Select article to confirm conditions of access and use.
bacteriophage community
cell cycle news & views
Bacteriophage 3:4, e26673; October/November/December 2013; © 2013 Landes Bioscience
Life in Science Björn H Lindqvist Email: [email protected]
graduated with a Filosofie kandidat degree (BS). DNA and the nature of the gene attracted me and I was ready to proceed with my studies leading to a Filosofie licentiat degree, a forerunner to a Filosofie doctor degree. As I was aware, so far very few in Sweden had embraced molecular biology at this time. Biochemistry at Stockholm University meant enzyme research and, somewhat reluctantly, I approached the biochemistry department headed by professor Karl Myrbäck.
Downloaded by [Selcuk Universitesi] at 03:00 31 January 2015
The Bertani Phage Lab and Microbial Genetics at the Karolinska Institute
Björn H Lindqvist, Professor Emeritus, Department of Molecular Biosciences, University of Oslo
I grew up in Stockholm, Sweden, during the 40s and 50s, embedded in wartime and social democracy. After graduation from Gymnasium in May 1957, I was drafted for almost a year into the Swedish Coastal Artillery as a cryptotechnician and stationed on the island of Gotland. A summer job at AB Atomenergi, Stockholm in 1958, analyzing uranium deposits, made me decide to apply for studies in chemistry at Stockholm University.
Stockholm University The first semester was dedicated to inorganic chemistry while physical chemistry was taught in the spring semester, all by a group of fine teachers. Professor Ölander acted as the supreme examiner. The department specialized in Xray crystallography. Organic chemistry was taught by Nils Lövgren, a co-discoverer of the anesthetic drug Xylocain. In the fall of 1959 some of us went on to study genetics. KG Lüning was the professor in the Department of Genetics, with roots that can be traced back to TH Morgan’s lab at Columbia University and Morgan’s Norwegian student OL Mohr. The research was mainly focused on radiation biology supported by the Swedish Atomic Research Council. As a major in genetics, I studied dominant lethal mutations in Drosophila after Xray exposure and left the studies impressed by Mendel’s scientific approach. In January 1961, I started to study microbiology. The course contained some microbial genetics such as phage lambda transduction. In June 1961, I
On my first day at Stockholm University, I received a call from Bengt Zacharias, one of my teachers in microbiology. He asked if I was interested in a licentiat-project in the laboratory of a newly recruited professor at the Karolinska Institute. His name was G Bertani and he studied bacterial viruses.1 It did not take long before I was in the Bertani’s office in the brand new Wallenberg Lab 60. I left the office as Bertani’s student and ready to start on the spot in the fall of 1961. At the end of 1964 I submitted my licentiat thesis in biochemistry at the Stockholm University titled “A physicochemical characterization of the super infecting phage P2 DNA”. My formal advisor was professor Karl Myrbäck, and Joe Bertani was my thesis advisor. He had given me the task to try to demonstrate the binding of the immunity substance, present in an E. coli P2 lysogen, to the super infecting P2 DNA. This was a highly relevant project, as it explored the nature of a repressor, as we know now. We hypothesized that the immunity substance was a protein that bound to and enclosed a substantial part of the super infecting DNA. By subjecting such complexes to nuclease treatment, we thought we might find the super infecting DNA more degradation resistant, compared with replicating P2 DNA. Equilibrium density gradient centrifugation to detect a density shift of the super infecting DNA was also tried. These approaches were obviously too crude. The intensity of seminars and the opportunity to meet all the visitors to the Bertani lab was exciting. James D Watson stopped by when he got the Nobel Prize in 1962, and many additional distinguished visitors also passed by. Betty Bertani held a docent position in the lab working on P2 and there were always a number of postdoctoral fellows present, mostly from the United States. At one point Martha Chase was there finishing her
PhD thesis. The other students were Birgitta Rönn, Marianne Wiman, and Gunnar Lindahl. Lisa Mörndal was Bertani’s loyal technician. I am grateful to Bengt Zacharias who led me to Joe and Betty Bertani. They introduced me to phage and became my most influential mentors together with Robert L Sinsheimer.
Single-Stranded DNA Replication at Caltech In the fall of 1964, Joe Bertani arranged for me to go to California Institute of Technology to work on the single-stranded DNA virus ØX174 as a research fellow in laboratory of professor Robert L Sinsheimer.2 I was fortunate to get a Fulbright travel grant, and when I arrived at Caltech in January 1965, the quest to understand the mechanism of singlestranded ØX174 DNA replication was ongoing. The Sinsheimer lab was bustling with people from all over the world. After a year or so, we discovered that mitomycin C pre- treatment of the E. coli host cell blocked its DNA synthesis while leaving that of ØX174 undisturbed. Now, pulse and chase experiments could be performed, and the results indicated that the double-stranded replicative form RFII was a direct precursor of viral single stranded DNA circles.3 This is probably my most important discovery ever. This and other observations led to “the rolling circle model of DNA replication” as formulated by Gilbert and Dressler.4 Caltech was a truly magnificent institution. After two and a half years in the Sinsheimer lab, my tenure was up, and I left for Sweden marked for life.
Microbiology at Stockholm University I arrived in Stockholm in August 1967 to take up a lectureship in microbiology at Stockholm University. During this time, I started to study P2 DNA replication together with Elisabeth Haggård—then a student in microbiology. I was, for the first time, confronted with the never-ending challenge of a scientist—how to get financial support. Erich Six, from the Department of Microbiology, School of Medicine, University of Iowa, spent the fall of 1968 as a visiting professor in Bertani’s laboratory at the Karolinska Institute. Six had discovered phage P4, a satellite phage, which needed a helper such as P2 for P4 particle formation, utilizing the structural late gene products of P2. He had now brought P4 to Stockholm and wondered if P4 infection of an E. coli P2 lysogen led to P2 DNA replication.
www.landesbioscience.com Bacteriophage
e26673-1
We did a few preliminary experiments, using the mitomycin C technique, in Stockholm and finally demonstrated lack of P2 DNA replication during a short visit of mine to Iowa City in the summer of 1969. We concluded that P4 taps the late genes of P2 by a mechanism of gene activation independent of P2 DNA replication.5 Soon, Richard Calendar, a student of P2, started to work on P4 and the family of P2–P4 workers grew. Later I had two fine sabbatical stays in his laboratory at UC Berkeley.
Downloaded by [Selcuk Universitesi] at 03:00 31 January 2015
Phage and Molecular Genetics above the Arctic Circle: University of Tromsø In May 1971, I defended my filosofie doctor thesis comprised of seven publications on ØX174, P2, and P4. Thomas Lindahl acted as my examiner. That very same year, I did transcriptional studies of P2 with Kjell Bøvre at the medical school, University of Oslo. He had just returned from Waclaw Szybalski’s lab at Madison where he had been studying phage lambda using RNA-DNA hybridization techniques. I had gotten a stipend that made the Oslo stay possible. In Oslo I was introduced to the plans of establishing a University at Tromsø, Norway. In 1972 I resigned from my lectureship and spent the whole year in Iowa City, continuing the collaboration with Erich Six until I was appointed docent in 1972 and from 1976 professor of microbiology in the medical school, at the brand new University of Tromsø, Norway. The town of Tromsø, located 69.65° north—way above the Arctic Circle—is the capital of North Norway. It is known as the gateway to the Arctic, as many of the famous attempts to reach the North Pole started here. We, the scientific vagabonds, now gathered at Tromsø, had other dreams—to build a fine University. Four of us had phage background, Finn Haugli, a student of Bill Dove at University of Wisconsin, Karin Carlsson, a student of Andrzej Kozinski at University of Pennsylvania, Kjell Bøvre and myself. During these years Erich Six made several lengthy visits to my lab, much to the benefit for the students like Svein Valla, my first student in Tromsø. Barry Egan came once for a summer to do transcriptional studies on phage 186, and Ken Murray brought me EcoR1 in a capillary tube during
a visit of him in 1974. Later we produced our own restriction enzymes.
Molecular Biology and Biotechnology at University of Oslo Three years in a row (1984–1986), I was invited to give a lecture and laboratory course in gene-technology at University of Oslo, and in 1986 I was invited to join the faculty at the Institute of Biology, University of Oslo, as professor of biotechnology. Classical biotechnology was now in transformation as a result of the recombinant DNA technology, spun off from the research efforts, largely in molecular genetics, decades before. Molecular genetics and recombinant DNA, prerequisites for the development of modern biotechnology, were lagging in Norway at this point. This was a challenge. Settled in Oslo, I decided to pursue my phage work with emphasis on virus assembly in the P2–P4 system. This platform promised to give the students depth and understanding at the molecular level of life, but at the same time fostering an entrepreneurial driven molecular biotechnology as exemplified by phage display. I started by setting up a course in molecular biology for the undergraduates in biology at University of Oslo. Since we had taught a course in molecular genetics in Tromsø from 1973, I tailored the course in Oslo after that and included an exercise in recombinant DNA. I also served as an adjunct professor at The Agricultural Research Council, where I set up a study program in molecular genetics, with special reference to phage, for a group of PhD students from the Agricultural University just south of Oslo. Over the years, I had several masters as well as PhD students contributing to the P2–P4 phage system, initially at Tromsø and from 1986 at Oslo. The discovery of the P4 scaffold, called Sid, which made us understand the redesign of the P2 size capsid into the smaller P4 capsid6 represents a memorable moment shared with the students. To promote biotechnology, a course was set up focusing on basic cellular and molecular phenomena in biology that had been harnessed into technologies and resulted in biotech companies. Rewardingly, a number of students went on to start companies, three of which led to
stock exchange listings. During that time, an in vitro peptide/protein display system was developed utilizing the P2 A gene.7 Biology of phage merits continued study to understand the diverse roles of phage in nature and for exploiting them as nanodevices. I have always enjoyed doing science and opening the doors of the incubators in the morning; looking for a “catch” was the thrill. My ultimate scientific goal is to understand how long-term memory is stored—yet another thrill.8
Acknowledgments I dedicate this article to Joe Bertani at his 90th birthday.
References 1. Bertani G. Lysogeny at mid-twentieth century: P1, P2, and other experimental systems. J Bacteriol 2004; 186:595-600; PMID:14729683; http://dx.doi.org/10.1128/ JB.186.3.595-600.2004 2. Sinsheimer RL. The Strands of a Life: The Science of DNA and the Art of Education University California Press, 1994 3. Lindqvist BH, Sinsheimer RL. The process of infection with bacteriophage phi X174. XVI. Synthesis of the replicative form and its relationship to viral singlestranded DNA synthesis. J Mol Biol 1968; 32:285-302; PMID:4868423;
http://dx.doi.org/10.1016/0022-
2836(68)90010-7 4. Gilbert W, Dressler D. DNA replication: the rolling circle model. Cold Spring Harb Symp Quant Biol 1968; 33:473-84; PMID:4891987; http://dx.doi.org/10.1101/ SQB.1968.033.01.055 5. Six EW, Lindqvist BH. Multiplication of bacteriophage P4 in the absence of replication of the DNA of its helper. Virology 1971; 43:8-15; PMID:5543291; http://dx.doi. org/10.1016/0042-6822(71)90219-4 6. Marvik OJ, Dokland T, Nøkling RH, Jacobsen E, Larsen T, Lindqvist BH. The capsid size-determining protein Sid forms an external scaffold on phage P4 procapsids. J Mol Biol 1995; 251:59-75; PMID:7643390; http://dx.doi. org/10.1006/jmbi.1995.0416 7. Lindqvist BH, Andrews D, Haggård-Ljungquist E, Isaksen, M. In vitro peptide or protein expression library. PCT patent 1998/037186 8. Lindqvist BH. The molecular biology of the Engram. Unpublished working hypothesis, University of Tromsø, 1976/77
e26673-2 Bacteriophage Volume 3 Issue 4
Bacteriophage Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/kbac20
Life in Science: Björn H Lindqvist a
Björn H Lindqvist a
Department of Molecular Biosciences; University of Oslo; Oslo, Norway Published online: 01 Oct 2013.
To cite this article: Björn H Lindqvist (2013) Life in Science: Björn H Lindqvist, Bacteriophage, 3:4, e26673, DOI: 10.4161/ bact.26673 To link to this article: http://dx.doi.org/10.4161/bact.26673
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Versions of published Taylor & Francis and Routledge Open articles and Taylor & Francis and Routledge Open Select articles posted to institutional or subject repositories or any other third-party website are without warranty from Taylor & Francis of any kind, either expressed or implied, including, but not limited to, warranties of merchantability, fitness for a particular purpose, or non-infringement. Any opinions and views expressed in this article are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor & Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions It is essential that you check the license status of any given Open and Open Select article to confirm conditions of access and use.
bacteriophage community
cell cycle news & views
Bacteriophage 3:4, e26673; October/November/December 2013; © 2013 Landes Bioscience
Life in Science Björn H Lindqvist Email: [email protected]
graduated with a Filosofie kandidat degree (BS). DNA and the nature of the gene attracted me and I was ready to proceed with my studies leading to a Filosofie licentiat degree, a forerunner to a Filosofie doctor degree. As I was aware, so far very few in Sweden had embraced molecular biology at this time. Biochemistry at Stockholm University meant enzyme research and, somewhat reluctantly, I approached the biochemistry department headed by professor Karl Myrbäck.
Downloaded by [Selcuk Universitesi] at 03:00 31 January 2015
The Bertani Phage Lab and Microbial Genetics at the Karolinska Institute
Björn H Lindqvist, Professor Emeritus, Department of Molecular Biosciences, University of Oslo
I grew up in Stockholm, Sweden, during the 40s and 50s, embedded in wartime and social democracy. After graduation from Gymnasium in May 1957, I was drafted for almost a year into the Swedish Coastal Artillery as a cryptotechnician and stationed on the island of Gotland. A summer job at AB Atomenergi, Stockholm in 1958, analyzing uranium deposits, made me decide to apply for studies in chemistry at Stockholm University.
Stockholm University The first semester was dedicated to inorganic chemistry while physical chemistry was taught in the spring semester, all by a group of fine teachers. Professor Ölander acted as the supreme examiner. The department specialized in Xray crystallography. Organic chemistry was taught by Nils Lövgren, a co-discoverer of the anesthetic drug Xylocain. In the fall of 1959 some of us went on to study genetics. KG Lüning was the professor in the Department of Genetics, with roots that can be traced back to TH Morgan’s lab at Columbia University and Morgan’s Norwegian student OL Mohr. The research was mainly focused on radiation biology supported by the Swedish Atomic Research Council. As a major in genetics, I studied dominant lethal mutations in Drosophila after Xray exposure and left the studies impressed by Mendel’s scientific approach. In January 1961, I started to study microbiology. The course contained some microbial genetics such as phage lambda transduction. In June 1961, I
On my first day at Stockholm University, I received a call from Bengt Zacharias, one of my teachers in microbiology. He asked if I was interested in a licentiat-project in the laboratory of a newly recruited professor at the Karolinska Institute. His name was G Bertani and he studied bacterial viruses.1 It did not take long before I was in the Bertani’s office in the brand new Wallenberg Lab 60. I left the office as Bertani’s student and ready to start on the spot in the fall of 1961. At the end of 1964 I submitted my licentiat thesis in biochemistry at the Stockholm University titled “A physicochemical characterization of the super infecting phage P2 DNA”. My formal advisor was professor Karl Myrbäck, and Joe Bertani was my thesis advisor. He had given me the task to try to demonstrate the binding of the immunity substance, present in an E. coli P2 lysogen, to the super infecting P2 DNA. This was a highly relevant project, as it explored the nature of a repressor, as we know now. We hypothesized that the immunity substance was a protein that bound to and enclosed a substantial part of the super infecting DNA. By subjecting such complexes to nuclease treatment, we thought we might find the super infecting DNA more degradation resistant, compared with replicating P2 DNA. Equilibrium density gradient centrifugation to detect a density shift of the super infecting DNA was also tried. These approaches were obviously too crude. The intensity of seminars and the opportunity to meet all the visitors to the Bertani lab was exciting. James D Watson stopped by when he got the Nobel Prize in 1962, and many additional distinguished visitors also passed by. Betty Bertani held a docent position in the lab working on P2 and there were always a number of postdoctoral fellows present, mostly from the United States. At one point Martha Chase was there finishing her
PhD thesis. The other students were Birgitta Rönn, Marianne Wiman, and Gunnar Lindahl. Lisa Mörndal was Bertani’s loyal technician. I am grateful to Bengt Zacharias who led me to Joe and Betty Bertani. They introduced me to phage and became my most influential mentors together with Robert L Sinsheimer.
Single-Stranded DNA Replication at Caltech In the fall of 1964, Joe Bertani arranged for me to go to California Institute of Technology to work on the single-stranded DNA virus ØX174 as a research fellow in laboratory of professor Robert L Sinsheimer.2 I was fortunate to get a Fulbright travel grant, and when I arrived at Caltech in January 1965, the quest to understand the mechanism of singlestranded ØX174 DNA replication was ongoing. The Sinsheimer lab was bustling with people from all over the world. After a year or so, we discovered that mitomycin C pre- treatment of the E. coli host cell blocked its DNA synthesis while leaving that of ØX174 undisturbed. Now, pulse and chase experiments could be performed, and the results indicated that the double-stranded replicative form RFII was a direct precursor of viral single stranded DNA circles.3 This is probably my most important discovery ever. This and other observations led to “the rolling circle model of DNA replication” as formulated by Gilbert and Dressler.4 Caltech was a truly magnificent institution. After two and a half years in the Sinsheimer lab, my tenure was up, and I left for Sweden marked for life.
Microbiology at Stockholm University I arrived in Stockholm in August 1967 to take up a lectureship in microbiology at Stockholm University. During this time, I started to study P2 DNA replication together with Elisabeth Haggård—then a student in microbiology. I was, for the first time, confronted with the never-ending challenge of a scientist—how to get financial support. Erich Six, from the Department of Microbiology, School of Medicine, University of Iowa, spent the fall of 1968 as a visiting professor in Bertani’s laboratory at the Karolinska Institute. Six had discovered phage P4, a satellite phage, which needed a helper such as P2 for P4 particle formation, utilizing the structural late gene products of P2. He had now brought P4 to Stockholm and wondered if P4 infection of an E. coli P2 lysogen led to P2 DNA replication.
www.landesbioscience.com Bacteriophage
e26673-1
We did a few preliminary experiments, using the mitomycin C technique, in Stockholm and finally demonstrated lack of P2 DNA replication during a short visit of mine to Iowa City in the summer of 1969. We concluded that P4 taps the late genes of P2 by a mechanism of gene activation independent of P2 DNA replication.5 Soon, Richard Calendar, a student of P2, started to work on P4 and the family of P2–P4 workers grew. Later I had two fine sabbatical stays in his laboratory at UC Berkeley.
Downloaded by [Selcuk Universitesi] at 03:00 31 January 2015
Phage and Molecular Genetics above the Arctic Circle: University of Tromsø In May 1971, I defended my filosofie doctor thesis comprised of seven publications on ØX174, P2, and P4. Thomas Lindahl acted as my examiner. That very same year, I did transcriptional studies of P2 with Kjell Bøvre at the medical school, University of Oslo. He had just returned from Waclaw Szybalski’s lab at Madison where he had been studying phage lambda using RNA-DNA hybridization techniques. I had gotten a stipend that made the Oslo stay possible. In Oslo I was introduced to the plans of establishing a University at Tromsø, Norway. In 1972 I resigned from my lectureship and spent the whole year in Iowa City, continuing the collaboration with Erich Six until I was appointed docent in 1972 and from 1976 professor of microbiology in the medical school, at the brand new University of Tromsø, Norway. The town of Tromsø, located 69.65° north—way above the Arctic Circle—is the capital of North Norway. It is known as the gateway to the Arctic, as many of the famous attempts to reach the North Pole started here. We, the scientific vagabonds, now gathered at Tromsø, had other dreams—to build a fine University. Four of us had phage background, Finn Haugli, a student of Bill Dove at University of Wisconsin, Karin Carlsson, a student of Andrzej Kozinski at University of Pennsylvania, Kjell Bøvre and myself. During these years Erich Six made several lengthy visits to my lab, much to the benefit for the students like Svein Valla, my first student in Tromsø. Barry Egan came once for a summer to do transcriptional studies on phage 186, and Ken Murray brought me EcoR1 in a capillary tube during
a visit of him in 1974. Later we produced our own restriction enzymes.
Molecular Biology and Biotechnology at University of Oslo Three years in a row (1984–1986), I was invited to give a lecture and laboratory course in gene-technology at University of Oslo, and in 1986 I was invited to join the faculty at the Institute of Biology, University of Oslo, as professor of biotechnology. Classical biotechnology was now in transformation as a result of the recombinant DNA technology, spun off from the research efforts, largely in molecular genetics, decades before. Molecular genetics and recombinant DNA, prerequisites for the development of modern biotechnology, were lagging in Norway at this point. This was a challenge. Settled in Oslo, I decided to pursue my phage work with emphasis on virus assembly in the P2–P4 system. This platform promised to give the students depth and understanding at the molecular level of life, but at the same time fostering an entrepreneurial driven molecular biotechnology as exemplified by phage display. I started by setting up a course in molecular biology for the undergraduates in biology at University of Oslo. Since we had taught a course in molecular genetics in Tromsø from 1973, I tailored the course in Oslo after that and included an exercise in recombinant DNA. I also served as an adjunct professor at The Agricultural Research Council, where I set up a study program in molecular genetics, with special reference to phage, for a group of PhD students from the Agricultural University just south of Oslo. Over the years, I had several masters as well as PhD students contributing to the P2–P4 phage system, initially at Tromsø and from 1986 at Oslo. The discovery of the P4 scaffold, called Sid, which made us understand the redesign of the P2 size capsid into the smaller P4 capsid6 represents a memorable moment shared with the students. To promote biotechnology, a course was set up focusing on basic cellular and molecular phenomena in biology that had been harnessed into technologies and resulted in biotech companies. Rewardingly, a number of students went on to start companies, three of which led to
stock exchange listings. During that time, an in vitro peptide/protein display system was developed utilizing the P2 A gene.7 Biology of phage merits continued study to understand the diverse roles of phage in nature and for exploiting them as nanodevices. I have always enjoyed doing science and opening the doors of the incubators in the morning; looking for a “catch” was the thrill. My ultimate scientific goal is to understand how long-term memory is stored—yet another thrill.8
Acknowledgments I dedicate this article to Joe Bertani at his 90th birthday.
References 1. Bertani G. Lysogeny at mid-twentieth century: P1, P2, and other experimental systems. J Bacteriol 2004; 186:595-600; PMID:14729683; http://dx.doi.org/10.1128/ JB.186.3.595-600.2004 2. Sinsheimer RL. The Strands of a Life: The Science of DNA and the Art of Education University California Press, 1994 3. Lindqvist BH, Sinsheimer RL. The process of infection with bacteriophage phi X174. XVI. Synthesis of the replicative form and its relationship to viral singlestranded DNA synthesis. J Mol Biol 1968; 32:285-302; PMID:4868423;
http://dx.doi.org/10.1016/0022-
2836(68)90010-7 4. Gilbert W, Dressler D. DNA replication: the rolling circle model. Cold Spring Harb Symp Quant Biol 1968; 33:473-84; PMID:4891987; http://dx.doi.org/10.1101/ SQB.1968.033.01.055 5. Six EW, Lindqvist BH. Multiplication of bacteriophage P4 in the absence of replication of the DNA of its helper. Virology 1971; 43:8-15; PMID:5543291; http://dx.doi. org/10.1016/0042-6822(71)90219-4 6. Marvik OJ, Dokland T, Nøkling RH, Jacobsen E, Larsen T, Lindqvist BH. The capsid size-determining protein Sid forms an external scaffold on phage P4 procapsids. J Mol Biol 1995; 251:59-75; PMID:7643390; http://dx.doi. org/10.1006/jmbi.1995.0416 7. Lindqvist BH, Andrews D, Haggård-Ljungquist E, Isaksen, M. In vitro peptide or protein expression library. PCT patent 1998/037186 8. Lindqvist BH. The molecular biology of the Engram. Unpublished working hypothesis, University of Tromsø, 1976/77
e26673-2 Bacteriophage Volume 3 Issue 4
