Kersten Hall - Academia.edu (original) (raw)
Online Publications by Kersten Hall
DNA fingerprinting, genetic therapy, gene editing: we often talk about genes, but do we know what... more DNA fingerprinting, genetic therapy, gene editing: we often talk about genes, but do we know what they are? The science of genetics began in the early twentieth century, but it was inspired by a paper published in 1866 by Gregor Mendel who never used the word himself. Philosophers and historians are still arguing about what exactly Mendel discovered. Here we introduce a stunning new online translation, published in the British Society for the History of Science new BSHS Translations series. The translation opens a window onto Mendel's original text in German, the language he used, and the world he inhabited. It shows that this Moravian friar did not work in solitary seclusion, but was deeply engaged with the intellectual, economic and political currents of his time.
Papers (Peer-reviewed publications) by Kersten Hall
DNA translated: Friedrich Miescher’s discovery of nuclein in its original context
British Journal for the History of Science, 2021
Papers by Kersten Hall
Journal of Virology, May 1, 2004
The herpesvirus saimiri open reading frame (ORF) 50 encodes two proteins, which activate transcri... more The herpesvirus saimiri open reading frame (ORF) 50 encodes two proteins, which activate transcription directly, following interactions with delayed-early (DE) promoters containing a specific motif. In this report, we demonstrate that ORF 50 contains a DNA binding domain that has homology to an AT hook DNA binding motif. Deletion analysis of this domain reduces ORF 50-mediated transactivation of the DE ORF 6 and ORF 57 promoters by 100 and 90%, respectively. Furthermore, gel retardation experiments demonstrated that the AT hook motif is required for binding the ORF 50 response element in the promoters of DE genes. Single site-directed mutagenesis of the AT hook revealed that mutation of the glycine residue at position 408 to an alanine reduces ORF 50 transactivation of the ORF 57 promoter by 40%. Moreover, the mutation of multiple basic residues in conjunction with the glycine residue within the core element of the AT hook abolishes ORF 50-mediated transactivation. In addition, p50GFP⌬AT-hook is capable of functioning as a trans-dominant mutant, leading to a reduction in virus production of approximately 50% compared to that for wild-type ORF 50.
Characterization of the herpesvirus saimiri ORF73 gene product
Journal of General Virology, Nov 1, 2000
Journal of Virology, Mar 1, 1998
We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptiona... more We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptional regulating genes in herpesvirus saimiri. ORF 50, a homolog of Epstein-Barr virus R protein, is a sequencespecific transactivator, whereas ORF 57 acts posttranscriptionally. In this report, we demonstrate that the ORF 57 gene is regulated by the ORF 50a gene product. We show that the ORF 57 gene is expressed at basal levels early in the virus replication cycle and that thereafter it is transactivated by the ORF 50a gene product, due to an increase in RNA levels. As it has been shown that the ORF 57 gene product downregulates ORF 50a due to the presence of its intron, these combined observations identify a feedback mechanism modulating gene expression in herpesvirus saimiri, whereby ORF 50a transcription is downregulated by the ORF 57 gene product, a gene which it specifically transactivates. Furthermore, we propose that the intron-containing ORF 57 gene downregulates itself by the same mechanism as that for ORF 50a, as both genes are downregulated at similar times during the replication cycle.
Journal of General Virology, 2004
The herpesvirus saimiri (HVS) ORF73 gene product shares limited homology with the ORF73 protein o... more The herpesvirus saimiri (HVS) ORF73 gene product shares limited homology with the ORF73 protein of Kaposi's sarcoma-associated herpesvirus (KSHV). ORF73 is expressed in an in vitro model of HVS latency, where the genome persists as a non-integrated circular episome. This suggests it may have a similar role to KSHV ORF73 in episomal maintenance, by tethering viral genomes to host-cell chromosomes. Here, the association of ORF73 with host mitotic chromosomes is described. Deletion analysis demonstrates that the distal 123 aa of the ORF73 protein are required for mitotic chromosomal localization and for self-association. Moreover, deletion of the extreme C terminus disrupts both self-association and host mitotic chromosome colocalization. This suggests that HVS ORF73 has a similar role to KSHV ORF73 in episomal maintenance and that association of ORF73 to host mitotic chromosomes is dependent on its ability to form multimers.
Journal of General Virology, Sep 1, 2000
Herpesvirus saimiri (HVS) ORF 57 is homologous to genes identified in all classes of herpesviruse... more Herpesvirus saimiri (HVS) ORF 57 is homologous to genes identified in all classes of herpesviruses. We have previously shown that ORF 57 encodes a multifunctional protein, responsible for both transactivation and repression of viral gene expression at a post-transcriptional level. This suggests that the ORF 57 protein shares some functional similarities with the herpes simplex virus IE63/ICP27 and Epstein-Barr virus Mta proteins. However, little is known about the functional domains responsible for the properties of ORF 57 due to the limited homology shared between these proteins. In this report, we have identified the functional domains responsible for transactivation and repression by the ORF 57 protein. We demonstrate that the carboxy terminus is required for ORF 57 transactivation, repression and an intense SC-35 nuclear spotting. This region contains two highly conserved motifs amongst its homologues, a zinc finger-like motif and a highly hydrophobic domain. We further show that the hydrophobic domain is required for transactivation and is also involved in nuclear localization of the ORF 57 protein, whereas the zinc finger-like domain is required for transactivation, repression and the intense SC-35 nuclear spotting.
Identification and Utilisation of the ORF 73 Latency-Associated Regulatory Region in Herpesvirus Saimiri-Based Vectors
Clinical science. Supplement (1979), Jul 1, 2002
Biochemical Society Transactions, May 1, 1997
Bell [married name Sawyer], Florence Ogilvy (1913–2000), biophysicist and molecular biologist
SHORT COMMUNICATION The gene product encoded by ORF
The herpesvirus saimiri (HVS) gene product encoded by ORF 57 shares limited C-terminal similarity... more The herpesvirus saimiri (HVS) gene product encoded by ORF 57 shares limited C-terminal similarity with herpes simplex virus 1 ICP27, a protein that has been demonstrated to be involved in the inhibition of host-cell splicing and is responsible for the redistribution of components of the spliceosome. It has previously been shown that ORF 57 can either activate or repress viral gene expression by a post-transcriptional mechanism. Furthermore, repression of gene expression by ORF 57 is dependent on the presence of an intron within the target gene coding region. In this report, it is shown that HVS infection results in the redistribution of the SC-35 splicing factor in the infected cell nucleus. Furthermore, the redistributed
Versuche über Pflanzen-Hybriden. Experiments on Plant Hybrids. New Translation with Commentary
Diky jeho experimentům s rostlinami hrachu, ktere byly poprve představeny v roce 1866, je Gregor ... more Diky jeho experimentům s rostlinami hrachu, ktere byly poprve představeny v roce 1866, je Gregor Mendel obvykle nazývan otcem moderni genetiky. Ale byl to opravdu jeho zaměr – objevit zakony dědicnosti a specificke vlastnosti genů – nebo mu byla tato motivace zpětně připisovana až na zakladě soucasných znalosti? Tyto otazky byly předmětem dlouho trvajici diskuze mezi historiky badajicimi v oblasti přirodnich věd, jejimž ustřednim tematem byl překlad Mendelova originalniho dila do anglictiny. Jeho nový překlad, doprovazený rozsahlým komentařem, který vydalo Mendelovo muzeum s podporou Britske spolecnosti pro historii vědy, ma snahu přinest cenne, významne a nove poznatky, ktere přispěji ke splněni dlouhodobeho ukolu – pochopeni a porozuměni Mendela.
On the Shoulders of Giants
Inference: International Review of Science, 2021
In discovering DNA’s structure, while James Watson and Francis Crick stood on the shoulders of Ro... more In discovering DNA’s structure, while James Watson and Francis Crick stood on the shoulders of Rosalind Franklin, there remains another unsung heroine upon whose shoulders Franklin herself stood.
Florence Bell—the ‘Housewife’ with x-ray vision
Notes and Records: the Royal Society Journal of the History of Science, 2021
After an award-winning portrayal by Nicole Kidman in a hit West End play, a Mars Rover named in h... more After an award-winning portrayal by Nicole Kidman in a hit West End play, a Mars Rover named in her honour, and recently a commemorative 50 pence coin released by the Royal Mint, Rosalind Franklin's crucial work in the discovery of the double-helical structure of DNA is well recognized. Far less well known, however, is the name of Florence Bell, the crystallographer who first showed that X-ray analysis could be used to reveal the regular, ordered structure of DNA. This paper explores her life and work, the legacy of which is ‘Photo 51’, the famous X-ray image of DNA taken by Rosalind Franklin and Raymond Gosling in 1952 that now features on the new 50 pence coin.
“In Praise of Wool”: The development of partition chromatography and its under-appreciated impact on molecular biology
Endeavour, 2020
The invention of partition chromatography by the biochemists Archer Martin and Richard Synge in 1... more The invention of partition chromatography by the biochemists Archer Martin and Richard Synge in 1941 offered crucial insights into the structure and function of DNA, insights at least as important as those from X-ray crystallography. Even so, the role that partition chromatography played in molecular biological studies is far less well known. Using new archival material, this article describes the origins of Martin and Synge's work, arguing that their achievement was far more than a new technical innovation; it went on to have a profound impact on the development of molecular biology to an extent that scholars have insufficiently appreciated.
Journal of Virology, 1999
The herpesvirus saimiri open reading frame (ORF) 50 produces two transcripts. The first is splice... more The herpesvirus saimiri open reading frame (ORF) 50 produces two transcripts. The first is spliced, contains a single intron, and is detected at early times during the productive cycle, whereas the second is expressed later and is produced from a promoter within the second exon. Analysis of their gene products has shown that they function as sequence specific transactivators. In this report, we demonstrate that the carboxy terminus of ORF 50b contains an activation domain which is essential for transactivation. This domain contains positionally conserved hydrophobic residues found in a number of activation domains, including the herpes simplex virus VP16 and the Epstein-Barr virus R proteins. Mutational analysis of this domain demonstrates that these conserved hydrophobic residues are essential for ORF 50 transactivation capability. Furthermore, this domain is required for the interaction between the ORF 50 proteins and the basal transcription factor TATA-binding protein.
Journal of Virology, 1998
We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptiona... more We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptional regulating genes in herpesvirus saimiri. ORF 50, a homolog of Epstein-Barr virus R protein, is a sequence-specific transactivator, whereas ORF 57 acts posttranscriptionally. In this report, we demonstrate that the ORF 57 gene is regulated by the ORF 50a gene product. We show that the ORF 57 gene is expressed at basal levels early in the virus replication cycle and that thereafter it is transactivated by the ORF 50a gene product, due to an increase in RNA levels. As it has been shown that the ORF 57 gene product downregulates ORF 50a due to the presence of its intron, these combined observations identify a feedback mechanism modulating gene expression in herpesvirus saimiri, whereby ORF 50a transcription is downregulated by the ORF 57 gene product, a gene which it specifically transactivates. Furthermore, we propose that the intron-containing ORF 57 gene downregulates itself by the same...
Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences, 2016
History and Philosophy of the Life Sciences, 2018
British Journal of Cancer, 2000
DNA fingerprinting, genetic therapy, gene editing: we often talk about genes, but do we know what... more DNA fingerprinting, genetic therapy, gene editing: we often talk about genes, but do we know what they are? The science of genetics began in the early twentieth century, but it was inspired by a paper published in 1866 by Gregor Mendel who never used the word himself. Philosophers and historians are still arguing about what exactly Mendel discovered. Here we introduce a stunning new online translation, published in the British Society for the History of Science new BSHS Translations series. The translation opens a window onto Mendel's original text in German, the language he used, and the world he inhabited. It shows that this Moravian friar did not work in solitary seclusion, but was deeply engaged with the intellectual, economic and political currents of his time.
DNA translated: Friedrich Miescher’s discovery of nuclein in its original context
British Journal for the History of Science, 2021
Journal of Virology, May 1, 2004
The herpesvirus saimiri open reading frame (ORF) 50 encodes two proteins, which activate transcri... more The herpesvirus saimiri open reading frame (ORF) 50 encodes two proteins, which activate transcription directly, following interactions with delayed-early (DE) promoters containing a specific motif. In this report, we demonstrate that ORF 50 contains a DNA binding domain that has homology to an AT hook DNA binding motif. Deletion analysis of this domain reduces ORF 50-mediated transactivation of the DE ORF 6 and ORF 57 promoters by 100 and 90%, respectively. Furthermore, gel retardation experiments demonstrated that the AT hook motif is required for binding the ORF 50 response element in the promoters of DE genes. Single site-directed mutagenesis of the AT hook revealed that mutation of the glycine residue at position 408 to an alanine reduces ORF 50 transactivation of the ORF 57 promoter by 40%. Moreover, the mutation of multiple basic residues in conjunction with the glycine residue within the core element of the AT hook abolishes ORF 50-mediated transactivation. In addition, p50GFP⌬AT-hook is capable of functioning as a trans-dominant mutant, leading to a reduction in virus production of approximately 50% compared to that for wild-type ORF 50.
Characterization of the herpesvirus saimiri ORF73 gene product
Journal of General Virology, Nov 1, 2000
Journal of Virology, Mar 1, 1998
We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptiona... more We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptional regulating genes in herpesvirus saimiri. ORF 50, a homolog of Epstein-Barr virus R protein, is a sequencespecific transactivator, whereas ORF 57 acts posttranscriptionally. In this report, we demonstrate that the ORF 57 gene is regulated by the ORF 50a gene product. We show that the ORF 57 gene is expressed at basal levels early in the virus replication cycle and that thereafter it is transactivated by the ORF 50a gene product, due to an increase in RNA levels. As it has been shown that the ORF 57 gene product downregulates ORF 50a due to the presence of its intron, these combined observations identify a feedback mechanism modulating gene expression in herpesvirus saimiri, whereby ORF 50a transcription is downregulated by the ORF 57 gene product, a gene which it specifically transactivates. Furthermore, we propose that the intron-containing ORF 57 gene downregulates itself by the same mechanism as that for ORF 50a, as both genes are downregulated at similar times during the replication cycle.
Journal of General Virology, 2004
The herpesvirus saimiri (HVS) ORF73 gene product shares limited homology with the ORF73 protein o... more The herpesvirus saimiri (HVS) ORF73 gene product shares limited homology with the ORF73 protein of Kaposi's sarcoma-associated herpesvirus (KSHV). ORF73 is expressed in an in vitro model of HVS latency, where the genome persists as a non-integrated circular episome. This suggests it may have a similar role to KSHV ORF73 in episomal maintenance, by tethering viral genomes to host-cell chromosomes. Here, the association of ORF73 with host mitotic chromosomes is described. Deletion analysis demonstrates that the distal 123 aa of the ORF73 protein are required for mitotic chromosomal localization and for self-association. Moreover, deletion of the extreme C terminus disrupts both self-association and host mitotic chromosome colocalization. This suggests that HVS ORF73 has a similar role to KSHV ORF73 in episomal maintenance and that association of ORF73 to host mitotic chromosomes is dependent on its ability to form multimers.
Journal of General Virology, Sep 1, 2000
Herpesvirus saimiri (HVS) ORF 57 is homologous to genes identified in all classes of herpesviruse... more Herpesvirus saimiri (HVS) ORF 57 is homologous to genes identified in all classes of herpesviruses. We have previously shown that ORF 57 encodes a multifunctional protein, responsible for both transactivation and repression of viral gene expression at a post-transcriptional level. This suggests that the ORF 57 protein shares some functional similarities with the herpes simplex virus IE63/ICP27 and Epstein-Barr virus Mta proteins. However, little is known about the functional domains responsible for the properties of ORF 57 due to the limited homology shared between these proteins. In this report, we have identified the functional domains responsible for transactivation and repression by the ORF 57 protein. We demonstrate that the carboxy terminus is required for ORF 57 transactivation, repression and an intense SC-35 nuclear spotting. This region contains two highly conserved motifs amongst its homologues, a zinc finger-like motif and a highly hydrophobic domain. We further show that the hydrophobic domain is required for transactivation and is also involved in nuclear localization of the ORF 57 protein, whereas the zinc finger-like domain is required for transactivation, repression and the intense SC-35 nuclear spotting.
Identification and Utilisation of the ORF 73 Latency-Associated Regulatory Region in Herpesvirus Saimiri-Based Vectors
Clinical science. Supplement (1979), Jul 1, 2002
Biochemical Society Transactions, May 1, 1997
Bell [married name Sawyer], Florence Ogilvy (1913–2000), biophysicist and molecular biologist
SHORT COMMUNICATION The gene product encoded by ORF
The herpesvirus saimiri (HVS) gene product encoded by ORF 57 shares limited C-terminal similarity... more The herpesvirus saimiri (HVS) gene product encoded by ORF 57 shares limited C-terminal similarity with herpes simplex virus 1 ICP27, a protein that has been demonstrated to be involved in the inhibition of host-cell splicing and is responsible for the redistribution of components of the spliceosome. It has previously been shown that ORF 57 can either activate or repress viral gene expression by a post-transcriptional mechanism. Furthermore, repression of gene expression by ORF 57 is dependent on the presence of an intron within the target gene coding region. In this report, it is shown that HVS infection results in the redistribution of the SC-35 splicing factor in the infected cell nucleus. Furthermore, the redistributed
Versuche über Pflanzen-Hybriden. Experiments on Plant Hybrids. New Translation with Commentary
Diky jeho experimentům s rostlinami hrachu, ktere byly poprve představeny v roce 1866, je Gregor ... more Diky jeho experimentům s rostlinami hrachu, ktere byly poprve představeny v roce 1866, je Gregor Mendel obvykle nazývan otcem moderni genetiky. Ale byl to opravdu jeho zaměr – objevit zakony dědicnosti a specificke vlastnosti genů – nebo mu byla tato motivace zpětně připisovana až na zakladě soucasných znalosti? Tyto otazky byly předmětem dlouho trvajici diskuze mezi historiky badajicimi v oblasti přirodnich věd, jejimž ustřednim tematem byl překlad Mendelova originalniho dila do anglictiny. Jeho nový překlad, doprovazený rozsahlým komentařem, který vydalo Mendelovo muzeum s podporou Britske spolecnosti pro historii vědy, ma snahu přinest cenne, významne a nove poznatky, ktere přispěji ke splněni dlouhodobeho ukolu – pochopeni a porozuměni Mendela.
On the Shoulders of Giants
Inference: International Review of Science, 2021
In discovering DNA’s structure, while James Watson and Francis Crick stood on the shoulders of Ro... more In discovering DNA’s structure, while James Watson and Francis Crick stood on the shoulders of Rosalind Franklin, there remains another unsung heroine upon whose shoulders Franklin herself stood.
Florence Bell—the ‘Housewife’ with x-ray vision
Notes and Records: the Royal Society Journal of the History of Science, 2021
After an award-winning portrayal by Nicole Kidman in a hit West End play, a Mars Rover named in h... more After an award-winning portrayal by Nicole Kidman in a hit West End play, a Mars Rover named in her honour, and recently a commemorative 50 pence coin released by the Royal Mint, Rosalind Franklin's crucial work in the discovery of the double-helical structure of DNA is well recognized. Far less well known, however, is the name of Florence Bell, the crystallographer who first showed that X-ray analysis could be used to reveal the regular, ordered structure of DNA. This paper explores her life and work, the legacy of which is ‘Photo 51’, the famous X-ray image of DNA taken by Rosalind Franklin and Raymond Gosling in 1952 that now features on the new 50 pence coin.
“In Praise of Wool”: The development of partition chromatography and its under-appreciated impact on molecular biology
Endeavour, 2020
The invention of partition chromatography by the biochemists Archer Martin and Richard Synge in 1... more The invention of partition chromatography by the biochemists Archer Martin and Richard Synge in 1941 offered crucial insights into the structure and function of DNA, insights at least as important as those from X-ray crystallography. Even so, the role that partition chromatography played in molecular biological studies is far less well known. Using new archival material, this article describes the origins of Martin and Synge's work, arguing that their achievement was far more than a new technical innovation; it went on to have a profound impact on the development of molecular biology to an extent that scholars have insufficiently appreciated.
Journal of Virology, 1999
The herpesvirus saimiri open reading frame (ORF) 50 produces two transcripts. The first is splice... more The herpesvirus saimiri open reading frame (ORF) 50 produces two transcripts. The first is spliced, contains a single intron, and is detected at early times during the productive cycle, whereas the second is expressed later and is produced from a promoter within the second exon. Analysis of their gene products has shown that they function as sequence specific transactivators. In this report, we demonstrate that the carboxy terminus of ORF 50b contains an activation domain which is essential for transactivation. This domain contains positionally conserved hydrophobic residues found in a number of activation domains, including the herpes simplex virus VP16 and the Epstein-Barr virus R proteins. Mutational analysis of this domain demonstrates that these conserved hydrophobic residues are essential for ORF 50 transactivation capability. Furthermore, this domain is required for the interaction between the ORF 50 proteins and the basal transcription factor TATA-binding protein.
Journal of Virology, 1998
We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptiona... more We have previously demonstrated that open reading frame (ORF) 50 and ORF 57 encode transcriptional regulating genes in herpesvirus saimiri. ORF 50, a homolog of Epstein-Barr virus R protein, is a sequence-specific transactivator, whereas ORF 57 acts posttranscriptionally. In this report, we demonstrate that the ORF 57 gene is regulated by the ORF 50a gene product. We show that the ORF 57 gene is expressed at basal levels early in the virus replication cycle and that thereafter it is transactivated by the ORF 50a gene product, due to an increase in RNA levels. As it has been shown that the ORF 57 gene product downregulates ORF 50a due to the presence of its intron, these combined observations identify a feedback mechanism modulating gene expression in herpesvirus saimiri, whereby ORF 50a transcription is downregulated by the ORF 57 gene product, a gene which it specifically transactivates. Furthermore, we propose that the intron-containing ORF 57 gene downregulates itself by the same...
Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences, 2016
History and Philosophy of the Life Sciences, 2018
British Journal of Cancer, 2000
Journal of General Virology, 1999
The herpesvirus saimiri (HVS) gene product encoded by ORF 57 shares limited C-terminal similarity... more The herpesvirus saimiri (HVS) gene product encoded by ORF 57 shares limited C-terminal similarity with herpes simplex virus 1 ICP27, a protein that has been demonstrated to be involved in the inhibition of host-cell splicing and is responsible for the redistribution of components of the spliceosome. It has previously been shown that ORF 57 can either activate or repress viral gene expression by a post-transcriptional mechanism. Furthermore, repression of gene expression by ORF 57 is dependent on the presence of an intron within the target gene coding region. In this report, it is shown that HVS infection results in the redistribution of the SC-35 splicing factor in the infected cell nucleus. Furthermore, the redistributed SC-35 colocalized with the ORF 57 protein product and expression of the protein alone was sufficient to cause the redistribution of the spliceosome components. These results suggest that the mechanism by which ORF 57 downregulates expression of intron-containing genes involves the redistribution of the spliceosome complex. Herpesvirus saimiri (HVS) is a lymphotropic rhadinovirus (γ # herpesvirus) of squirrel monkeys (Saimiri sciureus) that persistently infects its natural host without causing any obvious disease. However, HVS infection of other species of New World primates results in fulminant, polyclonal T-cell lymphomas and lymphoproliferative diseases (Fleckenstein & Desrosiers, 1982). HVS is also capable of transforming simian and human T lymphocytes to continuous growth in vitro (Beisinger et al., 1992). Analysis of the genome of HVS (strain A11) indicates that it shares significant similarity with the herpesviruses Epstein-Barr virus (EBV), bovine herpesvirus-4, Kaposi's sarcoma-associated herpesvirus (human herpesvirus
Latency-associated regulatory region from Herpesvirus saimiri (HVS)