Dr. Elizabeth (Betty) Kutter is a phage biologist based at the Evergreen State College in Olympia, Washington, USA, where she is a Professor Emeritus. She led the T4 Genome Sequencing project, and organized the biennial Evergreen International Phage Biology meetings that draw hundreds of phage researchers from all over the world.
Kutter attended Garfield High School in Seattle from 1953 to 1958. [1] Her father was an electrical engineer working at Boeing, and she credits him for her mathematical ability. [1] From 1956 to 1957 she traveled as an exchange student to Braunschweig, Germany. [1] After she finished high school, she did her bachelor's degree in theoretical mathematics at the University of Washington in Seattle, where she graduated top in her class [1] in 1962. [2]
From here, she moved to the University of Rochester in New York where she completed her PhD in the Department of Radiation Biology and Biophysics in 1968. [2] Although initially unsure about the direction her research should take, a lunch with visiting postdoctoral John Wiberg, who was then working in the lab of Salvador Luria, clarified her interest in bacteriophages. [1] He moved to Rochester and she completed her studies as his first student, writing her thesis on the topic of how T4 phage hijacks the metabolism of its host. [3] Salvador Luria would later quote her PhD research in his Nobel Prize talk. [4] [1]
During her university studies, she married German astrophysicist G Siegfried Kutter, and had two sons. [1]
From 1969 to 1972, she worked in the lab of Rolf Benzinger at the University of Virginia. [3] She was awarded a grant from the National Science Foundation (NSF), and later a grant from the National Institute of Health (NIH). There was little support for women in the department at this time, and although she applied for a faculty position, her application was denied on the basis that it was not a suitable position for a young mother. [1]
In 1972, Kutter met with two deans of a new college in Washington, the Evergreen State College, who were in Virginia on a recruitment trip. [1] Both her and her husband were offered jobs as faculty, and she moved to Olympia with her family at the start of 1973 to set up a new lab, bringing her NIH grant with her. [3] Her early work focused on molecular biology and specifically on T4, and in 1975 she joined the National Recombinant DNA Advisory Committee. [3] In 1978 she took a sabbatical year to work with Bruce Alberts at UC San Francisco, [3] and it was this work that resulted in her leading the T4 genome sequencing project alongside collaborators from the USSR, Japan, and Germany, [5] including Gisela Mosig. [1] At just under 169 kB, the T4 genome was the largest ever sequenced at this time, and the effort took fifteen years. [1]
In 1990, Kutter participated in a four-month research exchange with the USSR Academy of Sciences. [3] It was here that she first learnt about phage therapy, and this led to several trips to Tbilisi and a close collaborative relationship with scientists at the Eliava Institute. [5] In 1996, she set up the Phagebiotics Research Foundation, with the aim to publicize and support international phage therapy research. [6]
Intended as a successor to the regular meeting held by the Phage Group at the Cold Spring Harbour Laboratory, the first West Coast T4 meeting was held at the Evergreen Bacteriophage Lab in 1975. [3] This later developed into the biennial Evergreen International Phage Biology meetings. These meetings draw hundreds of participants from all over the world. [7] Much like Kutter's work more generally, their early incarnations were focused on T4 phage, and they later expanded to be about phage research more broadly. [5] The most recent meeting was held in 2021. [8]
A bacteriophage, also known informally as a phage, is a virus that infects and replicates within bacteria and archaea. The term was derived from bacteria and the Ancient Greek word φαγεῖν, meaning 'to devour'. Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.
Viral evolution is a subfield of evolutionary biology and virology that is specifically concerned with the evolution of viruses. Viruses have short generation times, and many—in particular RNA viruses—have relatively high mutation rates. Although most viral mutations confer no benefit and often even prove deleterious to viruses, the rapid rate of viral mutation combined with natural selection allows viruses to quickly adapt to changes in their host environment. In addition, because viruses typically produce many copies in an infected host, mutated genes can be passed on to many offspring quickly. Although the chance of mutations and evolution can change depending on the type of virus, viruses overall have high chances for mutations.
Phage therapy, viral phage therapy, or phagotherapy is the therapeutic use of bacteriophages for the treatment of pathogenic bacterial infections. This therapeutic approach emerged at the beginning of the 20th century but was progressively replaced by the use of antibiotics in most parts of the world after the Second World War. Bacteriophages, known as phages, are a form of virus that attach to bacterial cells and inject their genome into the cell. The bacteria's production of the viral genome interferes with its ability to function, halting the bacterial infection. The bacterial cell causing the infection is unable to reproduce and instead produces additional phages. Phages are very selective in the strains of bacteria they are effective against.
Escherichia virus T4 is a species of bacteriophages that infect Escherichia coli bacteria. It is a double-stranded DNA virus in the subfamily Tevenvirinae of the family Straboviridae. T4 is capable of undergoing only a lytic life cycle and not the lysogenic life cycle. The species was formerly named T-even bacteriophage, a name which also encompasses, among other strains, Enterobacteria phage T2, Enterobacteria phage T4 and Enterobacteria phage T6.
DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-polymerase or by helicase in front of the progressing replication fork. It is the only known enzyme to actively contribute negative supercoiling to DNA, while it also is capable of relaxing positive supercoils. It does so by looping the template to form a crossing, then cutting one of the double helices and passing the other through it before releasing the break, changing the linking number by two in each enzymatic step. This process occurs in bacteria, whose single circular DNA is cut by DNA gyrase and the two ends are then twisted around each other to form supercoils. Gyrase is also found in eukaryotic plastids: it has been found in the apicoplast of the malarial parasite Plasmodium falciparum and in chloroplasts of several plants. Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, novobiocin, albicidin, and ciprofloxacin.
Bacteriophage T7 is a bacteriophage, a virus that infects bacteria. It infects most strains of Escherichia coli and relies on these hosts to propagate. Bacteriophage T7 has a lytic life cycle, meaning that it destroys the cell it infects. It also possesses several properties that make it an ideal phage for experimentation: its purification and concentration have produced consistent values in chemical analyses; it can be rendered noninfectious by exposure to UV light; and it can be used in phage display to clone RNA binding proteins.
Marlene Belfort is an American biochemist known for her research on the factors that interrupt genes and proteins. She is a fellow of the American Academy of Arts and Sciences and has been admitted to the United States National Academy of Sciences.
In biology, co-adaptation is the process by which two or more species, genes or phenotypic traits undergo adaptation as a pair or group. This occurs when two or more interacting characteristics undergo natural selection together in response to the same selective pressure or when selective pressures alter one characteristic and consecutively alter the interactive characteristic. These interacting characteristics are only beneficial when together, sometimes leading to increased interdependence. Co-adaptation and coevolution, although similar in process, are not the same; co-adaptation refers to the interactions between two units, whereas co-evolution refers to their evolutionary history. Co-adaptation and its examples are often seen as evidence for co-evolution.
A concatemer is a long continuous DNA molecule that contains multiple copies of the same DNA sequence linked in series. These polymeric molecules are usually copies of an entire genome linked end to end and separated by cos sites. Concatemers are frequently the result of rolling circle replication, and may be seen in the late stage of infection of bacteria by phages. As an example, if the genes in the phage DNA are arranged ABC, then in a concatemer the genes would be ABCABCABCABC and so on. They are further broken by ribozymes.
Bacteriophage (phage) are viruses of bacteria and arguably are the most numerous "organisms" on Earth. The history of phage study is captured, in part, in the books published on the topic. This is a list of over 100 monographs on or related to phages.
P1 is a temperate bacteriophage that infects Escherichia coli and some other bacteria. When undergoing a lysogenic cycle the phage genome exists as a plasmid in the bacterium unlike other phages that integrate into the host DNA. P1 has an icosahedral head containing the DNA attached to a contractile tail with six tail fibers. The P1 phage has gained research interest because it can be used to transfer DNA from one bacterial cell to another in a process known as transduction. As it replicates during its lytic cycle it captures fragments of the host chromosome. If the resulting viral particles are used to infect a different host the captured DNA fragments can be integrated into the new host's genome. This method of in vivo genetic engineering was widely used for many years and is still used today, though to a lesser extent. P1 can also be used to create the P1-derived artificial chromosome cloning vector which can carry relatively large fragments of DNA. P1 encodes a site-specific recombinase, Cre, that is widely used to carry out cell-specific or time-specific DNA recombination by flanking the target DNA with loxP sites.
The phage group was an informal network of biologists centered on Max Delbrück that contributed heavily to bacterial genetics and the origins of molecular biology in the mid-20th century. The phage group takes its name from bacteriophages, the bacteria-infecting viruses that the group used as experimental model organisms. In addition to Delbrück, important scientists associated with the phage group include: Salvador Luria, Alfred Hershey, Seymour Benzer, Charles Steinberg, Gunther Stent, James D. Watson, Frank Stahl, and Renato Dulbecco.
Bacillus virus Φ29 is a double-stranded DNA (dsDNA) bacteriophage with a prolate icosahedral head and a short tail that belongs to the genus Salasvirus, order Caudovirales, and family Salasmaviridae. They are in the same order as phages PZA, Φ15, BS32, B103, M2Y (M2), Nf, and GA-1. First discovered in 1965, the Φ29 phage is the smallest Bacillus phage isolated to date and is among the smallest known dsDNA phages.
Autographiviridae is a family of viruses in the order Caudovirales. Bacteria serve as natural hosts. There are 373 species in this family, assigned to 9 subfamilies and 133 genera.
Enquatrovirus is a genus of bacteriophages in the order Caudovirales, in the family Podoviridae. Bacteria serve as natural hosts. There is currently only one species in this genus: the type species Escherichia virus N4.
Gisela Mosig was a German-American molecular biologist best known for her work with enterobacteria phage T4. She was among the first investigators to recognize the importance of recombination intermediates in establishing new DNA replication forks, a fundamental process in DNA replication.
Bacteriophage Mu, also known as mu phage or mu bacteriophage, is a muvirus of the family Myoviridae which has been shown to cause genetic transposition. It is of particular importance as its discovery in Escherichia coli by Larry Taylor was among the first observations of insertion elements in a genome. This discovery opened up the world to an investigation of transposable elements and their effects on a wide variety of organisms. While Mu was specifically involved in several distinct areas of research, the wider implications of transposition and insertion transformed the entire field of genetics.
The T4 Holin Family is a group of putative pore-forming proteins that does not belong to one of the seven holin superfamilies. T-even phage such as T4 use a holin-endolysin system for host cell lysis. Although the endolysin of phage T4 encoded by the e gene was identified in 1961, the holin was not characterized until 2001. A representative list of proteins belonging to the T4 holin family can be found in the Transporter Classification Database.
Grete Kellenberger-Gujer (1919–2011) was a Swiss molecular biologist known for her discoveries on genetic recombination and restriction modification system of DNA. She was a pioneer in the genetic analysis of bacteriophages and contributed to the early development of molecular biology.
Charles 'Charley' M. Steinberg was an immunobiologist and permanent member of the Basel Institute for Immunology. He was a former student of Max Delbrück. Notably he hosted Richard Feynman at Caltech when Feynman studied molecular biology, leading Feynman to remark that Charlie was “...the smartest guy I know”. He was instrumental in the discovery of V(D)J recombination, bacteriophage genetics as part of the phage group and co-discoverer of the amber-mutant of the T4 bacteriophage that led to the recognition of stop codons.