Catherine M. Green

Last updated

Catherine Green
OBE
Education Gravesend Grammar School for Girls
Alma mater Churchill College, Cambridge (BA)
Imperial Cancer Research Fund (PhD)
Known forBiochemistry
Genome sequencing
Scientific career
Institutions University of Sussex
Curie Institute
University of Oxford
Thesis The Rad24 checkpoint protein of Saccharomyces cerevisiae : a complex problem.
Doctoral advisor Noel F. Lowndes [1]

Catherine Mary Green OBE is an English biologist who is an Associate Professor in Chromosome Dynamics at the Wellcome Centre for Human Genetics at the University of Oxford. Her research considers chromosome stability during the replication of DNA. During the COVID-19 pandemic Green was part of the Oxford team who developed the Oxford–AstraZeneca COVID-19 vaccine.

Contents

Early life and education

Green grew up in Gravesend and attended Gravesend Grammar School for Girls. [2] [3] She was an undergraduate at Churchill College, Cambridge, where she has said that her love of science was solidified. [4] [2] After completing part II of the Natural Sciences Tripos and herewith obtaining a BA degree from Cambridge, Green was awarded an Imperial Cancer Research Fund (now Cancer Research UK) scholarship for her doctoral research. Green studied damaged DNA in yeast at the Clare Hall laboratories. [5] After earning her PhD degree from the University College London in 2000, Green moved to the Curie Institute, where she studied DNA damage in human cells as a Marie Curie Fellow. [2] Upon returning to the United Kingdom Green was appointed to the University of Sussex, where she studied DNA damage due to sunlight exposure. [2]

Research and career

Green was made a Cancer Research UK Research Fellow in the Department of Zoology at the University of Cambridge in 2008. [6] She held a Kaye Research Fellowship at Christ's College, Cambridge. [2] Her research considered the mechanisms of genome replication at the genetic and epigenetic levels. [6] During this replication process the mutations that are responsible for cancer can occur, or be fixed. Understanding the process that underpins this replication, and how cells control this replication, allows Green to better understand the development of cancer. [6] [7]

In 2012 Green moved to the University of Oxford, where she joined the Wellcome Centre for Human Genetics. Here Green expanded her work in genomics to encompass the genetic and epigenetic stability of DNA. [8] Green was made Monsanto Senior Research Fellow at Exeter College, Oxford in 2017. [9] She leads the core facility in Chromosome Dynamics at the Wellcome Centre. [10]

During the COVID-19 pandemic Green was part of the Jenner Institute team who developed a coronavirus disease vaccine. [11] The Jenner Institute vaccination platform had been prepared for the MERS and SARS outbreaks, and so was ready to respond quickly to the emerging disease. [9] Green worked with Sarah Gilbert on the production of the ChAdOx1 nCoV-19 vaccination. [12] The team started research in January 2020, and managed to identify a chimpanzee adenovirus vector (ChAdOx) that generated a strong immune response to SARS-CoV-2. [12] They used the SARS-CoV-2 genome that had beens sequenced by researchers in Wuhan. The adenovirus cannot replicate, so does not cause further infection, and instead acts as a vector to transfer the SARS-CoV-2 spike protein. [9] The spike protein, an external protein that enables the virus to enter cells, is responsible for the immune system response. In early April the team were awarded £22 million of funding from the Government of the United Kingdom to run human trials. [12] The vaccine underwent clinical trials in Oxford in April 2020, which were successful. [13] On 30 December 2020, the vaccine was approved for use in the UK. [14] More than 3 billion doses of the vaccine were supplied to countries worldwide. [15]

In 2021, Green and Sarah Gilbert published Vaxxers: the inside story of the Oxford AstraZeneca vaccine and the race against the virus. [16] [17]

Selected publications

Green has an h-index of 51 according to Google Scholar. [18] Her publications include:

Related Research Articles

<span class="mw-page-title-main">DNA replication</span> Biological process

In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part of biological inheritance. This is essential for cell division during growth and repair of damaged tissues, while it also ensures that each of the new cells receives its own copy of the DNA. The cell possesses the distinctive property of division, which makes replication of DNA essential.

<span class="mw-page-title-main">AstraZeneca</span> British pharmaceutical company

AstraZeneca plc (AZ) is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas including oncology, cardiovascular, gastrointestinal, infection, neuroscience, respiratory, and inflammation. It has been involved in developing the Oxford–AstraZeneca COVID-19 vaccine.

<i>Adenoviridae</i> Family of viruses

Adenoviruses are medium-sized, nonenveloped viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.

<span class="mw-page-title-main">DNA repair</span> Cellular mechanism

DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur. This can eventually lead to malignant tumors, or cancer as per the two-hit hypothesis.

<span class="mw-page-title-main">Pyrimidine dimer</span> Type of damage to DNA

Pyrimidine dimers represent molecular lesions originating from thymine or cytosine bases within DNA, resulting from photochemical reactions. These lesions, commonly linked to direct DNA damage, are induced by ultraviolet light (UV), particularly UVC, result in the formation of covalent bonds between adjacent nitrogenous bases along the nucleotide chain near their carbon–carbon double bonds, the photo-coupled dimers are fluorescent. Such dimerization, which can also occur in double-stranded RNA (dsRNA) involving uracil or cytosine, leads to the creation of cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts. These pre-mutagenic lesions modify the DNA helix structure, resulting in abnormal non-canonical base pairing and, consequently, adjacent thymines or cytosines in DNA will form a cyclobutane ring when joined together and cause a distortion in the DNA. This distortion prevents DNA replication and transcription mechanisms beyond the dimerization site.

Postreplication repair is the repair of damage to the DNA that takes place after replication.

<span class="mw-page-title-main">RAD9A</span> Protein-coding gene in the species Homo sapiens

Cell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by the RAD9A gene.Rad9 has been shown to induce G2 arrest in the cell cycle in response to DNA damage in yeast cells. Rad9 was originally found in budding yeast cells but a human homolog has also been found and studies have suggested that the molecular mechanisms of the S and G2 checkpoints are conserved in eukaryotes. Thus, what is found in yeast cells are likely to be similar in human cells.

<span class="mw-page-title-main">POLI</span> Protein-coding gene in the species Homo sapiens

DNA polymerase iota is an enzyme that in humans is encoded by the POLI gene. It is found in higher eukaryotes, and is believed to have arisen from a gene duplication from Pol η. Pol ι, is a Y family polymerase that is involved in translesion synthesis. It can bypass 6-4 pyrimidine adducts and abasic sites and has a high frequency of wrong base incorporation. Like many other Y family polymerases Pol ι, has low processivity, a large DNA binding pocket and doesn't undergo conformational changes when DNA binds. These attributes are what allow Pol ι to carry out its task as a translesion polymerase. Pol ι only uses Hoogsteen base pairing, during DNA synthesis, it will add adenine opposite to thymine in the syn conformation and can add both cytosine and thymine in the anti conformation across guanine, which it flips to the syn conformation.

<span class="mw-page-title-main">DNA polymerase lambda</span> Protein-coding gene in the species Homo sapiens

DNA polymerase lambda, also known as Pol λ, is an enzyme found in all eukaryotes. In humans, it is encoded by the POLL gene.

<span class="mw-page-title-main">TOPBP1</span> Protein-coding gene in the species Homo sapiens

DNA topoisomerase 2-binding protein 1 (TOPBP1) is a scaffold protein that in humans is encoded by the TOPBP1 gene.

<span class="mw-page-title-main">DNA polymerase eta</span> Protein-coding gene in the species Homo sapiens

DNA polymerase eta, is a protein that in humans is encoded by the POLH gene.

Genome instability refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy.

<span class="mw-page-title-main">Kataegis</span>

In molecular biology, kataegis describes a pattern of localized hypermutations identified in some cancer genomes, in which a large number of highly patterned basepair mutations occur in a small region of DNA. The mutational clusters are usually several hundred basepairs long, alternating between a long range of C→T substitutional pattern and a long range of G→A substitutional pattern. This suggests that kataegis is carried out on only one of the two template strands of DNA during replication. Compared to other cancer-related mutations, such as chromothripsis, kataegis is more commonly seen; it is not an accumulative process but likely happens during one cycle of replication.

DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a nucleobase missing from the backbone of DNA, or a chemically changed base such as 8-OHdG. DNA damage can occur naturally or via environmental factors, but is distinctly different from mutation, although both are types of error in DNA. DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of base pairs. DNA damages cause changes in the structure of the genetic material and prevents the replication mechanism from functioning and performing properly. The DNA damage response (DDR) is a complex signal transduction pathway which recognizes when DNA is damaged and initiates the cellular response to the damage.

DNA polymerase IV is a prokaryotic polymerase that is involved in mutagenesis and is encoded by the dinB gene. It exhibits no 3′→5′ exonuclease (proofreading) activity and hence is error prone. In E. coli, DNA polymerase IV is involved in non-targeted mutagenesis. Pol IV is a Family Y polymerase expressed by the dinB gene that is switched on via SOS induction caused by stalled polymerases at the replication fork. During SOS induction, Pol IV production is increased tenfold and one of the functions during this time is to interfere with Pol III holoenzyme processivity. This creates a checkpoint, stops replication, and allows time to repair DNA lesions via the appropriate repair pathway. Another function of Pol IV is to perform translesion synthesis at the stalled replication fork like, for example, bypassing N2-deoxyguanine adducts at a faster rate than transversing undamaged DNA. Cells lacking dinB gene have a higher rate of mutagenesis caused by DNA damaging agents.

<span class="mw-page-title-main">Stephen Jackson (biologist)</span> British biologist

Sir Stephen Philip Jackson, FRS, FMedSci is the Frederick James Quick Professor of Biology. He is a senior group leader at the Cancer Research UK Cambridge Institute and associate group leader at the Gurdon Institute, University of Cambridge.

<span class="mw-page-title-main">PrimPol</span> Protein-coding gene in the species Homo sapiens

PrimPol is a protein encoded by the PRIMPOL gene in humans. PrimPol is a eukaryotic protein with both DNA polymerase and DNA Primase activities involved in translesion DNA synthesis. It is the first eukaryotic protein to be identified with priming activity using deoxyribonucleotides. It is also the first protein identified in the mitochondria to have translesion DNA synthesis activities.

<span class="mw-page-title-main">Sarah Gilbert</span> English vaccinologist (born 1962)

Dame Sarah Catherine Gilbert FRS is an English vaccinologist who is a Professor of Vaccinology at the University of Oxford and co-founder of Vaccitech. She specialises in the development of vaccines against influenza and emerging viral pathogens. She led the development and testing of the universal flu vaccine, which underwent clinical trials in 2011.

<span class="mw-page-title-main">Jenner Institute</span> Vaccine research institute in Oxford

The Jenner Institute is a research institute on the Old Road Campus in Headington, east Oxford, England. It was formed in November 2005 through a partnership between the University of Oxford and the UK Institute for Animal Health. It is associated with the Nuffield Department of Medicine, in the Medical Sciences Division of Oxford University. The institute receives charitable support from the Jenner Vaccine Foundation.

<span class="mw-page-title-main">Oxford–AstraZeneca COVID-19 vaccine</span> Viral vector vaccine for prevention of COVID-19 by Oxford University and AstraZeneca

The Oxford–AstraZeneca COVID‑19 vaccine, sold under the brand names Covishield and Vaxzevria among others, is a viral vector vaccine for the prevention of COVID-19. It was developed in the United Kingdom by Oxford University and British-Swedish company AstraZeneca, using as a vector the modified chimpanzee adenovirus ChAdOx1. The vaccine is given by intramuscular injection. Studies carried out in 2020 showed that the efficacy of the vaccine is 76.0% at preventing symptomatic COVID-19 beginning at 22 days following the first dose and 81.3% after the second dose. A study in Scotland found that, for symptomatic COVID-19 infection after the second dose, the vaccine is 81% effective against the Alpha variant and 61% against the Delta variant.

References

  1. ↑ "Cell Division Cycle Laboratory". Imperial Cancer Research Fund. 2000. Archived from the original on 25 October 2000.
  2. 1 2 3 4 5 "Christ's College Magazine 2008". Issuu. Retrieved 24 April 2020.
  3. ↑ "Weekly Bulletin: Mayfield Grammar School" (PDF). Mayfield Grammar School . Retrieved 20 July 2021.
  4. ↑ "Churchill alumni listed in Queen's Birthday Honours". Churchill College, Cambridge . 11 June 2016. Retrieved 19 July 2021.
  5. ↑ Vialard, J E; Gilbert, C S; Green, C M; Lowndes, N F (1 October 1998). "The budding yeast Rad9 checkpoint protein is subjected to Mec1/Tel1-dependent hyperphosphorylation and interacts with Rad53 after DNA damage". The EMBO Journal. 17 (19): 5679–5688. doi:10.1093/emboj/17.19.5679. ISSN   0261-4189. PMC   1170896 . PMID   9755168.
  6. 1 2 3 "Dr Catherine Green PhD | Christs College Cambridge". www.christs.cam.ac.uk. Retrieved 24 April 2020.
  7. ↑ Oxford, N. D. M. (21 November 2014), Catherine Green: DNA replication and cancer , retrieved 24 April 2020
  8. ↑ "Department of Zoology, University of Cambridge, United Kingdom". Epigenesys. Retrieved 24 April 2020.
  9. 1 2 3 "Exeter Fellow Dr Catherine Green leads the production of a potential COVID-19 vaccine in Oxford". Exeter College. 6 April 2020. Retrieved 24 April 2020.
  10. ↑ "Catherine Green — Wellcome Centre for Human Genetics". www.well.ox.ac.uk. Retrieved 24 April 2020.
  11. ↑ "Hear from the Oxford COVID-19 vaccine team | Science Media Centre" . Retrieved 24 April 2020.
  12. 1 2 3 Hoare, Callum (2 April 2020). "Oxford University scientist tips miracle COVID-19 'neutraliser' for NHS frontline staff". Express.co.uk. Retrieved 24 April 2020.
  13. ↑ "Coronavirus vaccine: Professor behind trial tells James O'Brien what happens next". LBC. Retrieved 24 April 2020.
  14. ↑ "Covid-19: Oxford-AstraZeneca coronavirus vaccine approved for use in UK". BBC News. BBC. 30 December 2020. Retrieved 30 December 2020.
  15. ↑ "AstraZeneca withdraws Covid-19 vaccine, citing low demand". CNN . Retrieved 9 May 2024.
  16. ↑ Honigsbaum, Mark (11 July 2021). "Vaxxers by Sarah Gilbert and Catherine Green; Until Proven Safe by Geoff Manaugh and Nicola Twilley – reviews". The Guardian. Retrieved 12 June 2022.
  17. ↑ Ledford, Heidi (5 August 2021). "The COVID vaccine makers tell all". Nature. 596 (7870): 29–30. Bibcode:2021Natur.596...29L. doi:10.1038/d41586-021-02090-9. S2CID   236883504.
  18. ↑ "Catherine Green". Google Scholar . Retrieved 11 May 2024.
  19. ↑ Bienko, Marzena; Green, Catherine M.; Crosetto, Nicola; Rudolf, Fabian; Zapart, Grzegorz; Coull, Barry; Kannouche, Patricia; Wider, Gerhard; Peter, Matthias; Lehmann, Alan R.; Hofmann, Kay (16 December 2005). "Ubiquitin-Binding Domains in Y-Family Polymerases Regulate Translesion Synthesis". Science. 310 (5755): 1821–1824. Bibcode:2005Sci...310.1821B. doi:10.1126/science.1120615. ISSN   0036-8075. PMID   16357261. S2CID   10666348.
  20. ↑ Lehmann, Alan R.; Niimi, Atsuko; Ogi, Tomoo; Brown, Stephanie; Sabbioneda, Simone; Wing, Jonathan F.; Kannouche, Patricia L.; Green, Catherine M. (1 July 2007). "Translesion synthesis: Y-family polymerases and the polymerase switch". DNA Repair. Replication Fork Repair Processes. 6 (7): 891–899. doi:10.1016/j.dnarep.2007.02.003. ISSN   1568-7864. PMID   17363342.
  21. ↑ Gilbert, Christopher S; Green, Catherine M; Lowndes, Noel F (1 July 2001). "Budding Yeast Rad9 Is an ATP-Dependent Rad53 Activating Machine". Molecular Cell. 8 (1): 129–136. doi: 10.1016/S1097-2765(01)00267-2 . ISSN   1097-2765. PMID   11511366.
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