David Glover | |
---|---|
Born | David Moore Glover March 28, 1948 [1] |
Nationality | British |
Education | Broadway Technical Grammar School, Barnsley [1] |
Alma mater | University of Cambridge (BA, ScD) University of London (PhD) |
Spouse | |
Awards | EMBO Member (1978) [2] |
Scientific career | |
Fields | Mitosis Meiosis Centrosomes [3] |
Institutions | Imperial Cancer Research Fund University College London Stanford University Imperial College University of Dundee University of Cambridge California Institute of Technology |
Thesis | The synthesis of polyoma virus specific RNA in mouse cells |
David Moore Glover FRS FRSE (born 28 March 1948) is a British geneticist and Research Professor of Biology and Biological Engineering at the California Institute of Technology. [4] He served as Balfour Professor of Genetics at the University of Cambridge, a Wellcome Trust investigator in the Department of Genetics at the University of Cambridge, and Fellow of Fitzwilliam College, Cambridge. He serves as the first editor-in-chief of the open-access journal Open Biology published by the Royal Society. [5] [6] [7] [1] [3] [8]
Glover was educated at Broadway Technical Grammar School, Barnsley [1] and the University of Cambridge. [1] He undertook his PhD research in the Imperial Cancer Research Fund laboratories as a student of University College London. [9]
As a Damon Runyon Fellow at Stanford University he participated in the Recombinant DNA revolution and discovered sequences that interrupted the ribosomal genes of Drosophila . On establishing his independent laboratory at Imperial College London in 1975, he later showed that these were ancient transposable elements. Together with Peter Rigby, Jean Beggs and David Lane, he co-directed a combined research group exploiting the new techniques of recombinant DNA research. In 1978 he was elected Member of the European Molecular Biology Organization (EMBO). [2]
While at Imperial, Glover was awarded a 10-year personal fellowship from the UK's Cancer Research Campaign that allowed him open up a new area of research pioneering the use of Drosophila as a model in which to study cell cycle regulation. He began by characterising the duplication cycles of centrosomes in the rapid nuclear division cycles of Drosophila embryos. This led to genetic studies that allowed him to discover and name the Polo and Aurora protein kinases, required for the function of centrosomes at the poles of mitotic spindles. [10]
In 1989, he relinquished his position as Head of the Department of Biochemistry at Imperial to move to the University of Dundee, where with David and Birgitte Lane he established the Cancer Research Campaign Laboratories, Dundee. Here his work demonstrated Polo not only to be required at centrosomes in Drosophila but also for cytokinesis. In parallel studies, Glover found that in an organism as distant as fission yeast, Polo's counterpart, that he named Plo1, was also required to establish functional spindle pole bodies and cytokinesis rings. Remarkably, the localisation and function of Polo kinase at the centrosome, the kinetochore and the central spindle in cytokinesis was highly conserved in human cells where its expression was elevated in tumours. This led Glover to collaborations with Biotechnological and Pharmaceutical industries in developing small molecule inhibitors of Polo for use in cancer therapy.[ citation needed ]
In Dundee he continued to use Drosophila as a means to uncover new components of the mitotic apparatus and its regulatory circuits. These studies uncovered spindle pole molecules whose functions were regulated by Polo kinase; a germ line specific Cdc25 phosphatase that regulates meiotic entry; and demonstrated the roles of PP1 and PP2A protein phosphatases as negative mitotic regulators. His contribution to science in Scotland was recognised by his election to Fellow of the Royal Society of Edinburgh (FRSE).[ citation needed ]
In 1999, Glover moved to the University of Cambridge to become the 6th Arthur Balfour Professor of Genetics and Head of Department. In Cambridge he discovered the second main Aurora B kinase required for cells to progress through metaphase and used genetic approaches to identify and demonstrate the roles of the Greatwall kinase in inhibiting protein phosphase 2A during mitotic entry and progression. Over the past decade he has uncovered the major steps of centriole duplication by demonstrating that Polo-like-kinase 4 (Plk4) is its master regulator; Plk4 expression can drive the de novo formation of centrioles in unfertilised Drosophila eggs. In searching for Plk4's partners, his group identified Asterless (Cep152 in human cells) as required for bringing Plk4 to centrioles and an F-box protein, Slimb – a component of the SCF ubiquitin protein ligase, as responsible for targeting excess Plk4 for destruction. They showed that Plk4 phosphorylates the centriole protein Ana2/STIL to enable it to bind the "cartwheel protein" Sas6 and thus initiate procentriole formation, the first step of centriole duplication.[ citation needed ]
In 2019, the Glover Lab moved to the California Institute of Technology in USA. [11]
Glover's group are now[ when? ] studying the consequences of supernumerary centrosomes in a variety of mammalian tissues and their consequences for the balance of cell proliferation and differentiation in the skin and pancreas.
Glover married Magdalena Żernicka-Goetz in 2000. [1]
In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers (Pinophyta), flowering plants (angiosperms) and most fungi, and are only present in the male gametes of charophytes, bryophytes, seedless vascular plants, cycads, and Ginkgo. A bound pair of centrioles, surrounded by a highly ordered mass of dense material, called the pericentriolar material (PCM), makes up a structure called a centrosome.
In cell biology, mitosis is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintained. Therefore, mitosis is also known as equational division. In general, mitosis is preceded by S phase of interphase and is often followed by telophase and cytokinesis; which divides the cytoplasm, organelles and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis altogether define the mitotic (M) phase of a cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.
In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progression. The centrosome provides structure for the cell. The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes and therefore use other structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species.
In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.
The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.
Aurora kinases are serine/threonine kinases that are essential for cell proliferation. They are phosphotransferase enzymes that help the dividing cell dispense its genetic materials to its daughter cells. More specifically, Aurora kinases play a crucial role in cellular division by controlling chromatid segregation. Defects in this segregation can cause genetic instability, a condition which is highly associated with tumorigenesis. The first aurora kinases were identified in Drosophila melanogaster, where mutations led to failure of centrosome separation with the monopolar spindles reminiscent of the North Pole, suggesting the name aurora.
Cyclacel Pharmaceuticals Inc. is a biotechnology firm based in Berkeley Heights, New Jersey and Dundee, Scotland, developing cancer treatments. Cyclacel was founded in 1996 by David Lane, PhD.
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.
An asymmetric cell division produces two daughter cells with different cellular fates. This is in contrast to symmetric cell divisions which give rise to daughter cells of equivalent fates. Notably, stem cells divide asymmetrically to give rise to two distinct daughter cells: one copy of the original stem cell as well as a second daughter programmed to differentiate into a non-stem cell fate.
Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.
Polo-like kinases (Plks) are regulatory serine/threonin kinases of the cell cycle involved in mitotic entry, mitotic exit, spindle formation, cytokinesis, and meiosis. Only one Plk is found in the genomes of the fly Drosophila melanogaster (Polo), budding yeast (Cdc5) and fission yeast (Plo1). Vertebrates and other animals, however, have many Plk family members including Plk1, Plk2/Snk, Plk3/Prk/FnK, Plk4/Sak and Plk5. Of the vertebrate Plk family members, the mammalian Plk1 has been most extensively studied. During mitosis and cytokinesis, Plks associate with several structures including the centrosome, kinetochores, and the central spindle.
Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the PLK1 gene.
In enzymology, a polo kinase is a kinase enzyme i.e. one that catalyzes the chemical reaction
Pericentrin (kendrin), also known as PCNT and pericentrin-B (PCNTB), is a protein which in humans is encoded by the PCNT gene on chromosome 21. This protein localizes to the centrosome and recruits proteins to the pericentriolar matrix (PCM) to ensure proper centrosome and mitotic spindle formation, and thus, uninterrupted cell cycle progression. This gene is implicated in many diseases and disorders, including congenital disorders such as microcephalic osteodysplastic primordial dwarfism type II (MOPDII) and Seckel syndrome.
Aurora kinase C, also Serine/threonine-protein kinase 13 is an enzyme that in humans is encoded by the AURKC gene.
Serine/threonine-protein kinase PLK4 also known as polo-like kinase 4 is an enzyme that in humans is encoded by the PLK4 gene. The Drosophila homolog is SAK, the C elegans homolog is zyg-1, and the Xenopus homolog is Plx4.
Centrosomal protein of 152 kDa, also known as Cep152, is a protein that in humans is encoded by the CEP152 gene. It is the ortholog of the Drosophila melanogaster gene asterless (asl) and both are required for centriole duplication.
Centrosomes are the major microtubule organizing centers (MTOC) in mammalian cells. Failure of centrosome regulation can cause mistakes in chromosome segregation and is associated with aneuploidy. A centrosome is composed of two orthogonal cylindrical protein assemblies, called centrioles, which are surrounded by a protein dense amorphous cloud of pericentriolar material (PCM). The PCM is essential for nucleation and organization of microtubules. The centrosome cycle is important to ensure that daughter cells receive a centrosome after cell division. As the cell cycle progresses, the centrosome undergoes a series of morphological and functional changes. Initiation of the centrosome cycle occurs early in the cell cycle in order to have two centrosomes by the time mitosis occurs.
Sfi1 homolog, spindle assembly associated (yeast) is a protein that in humans is encoded by the SFI1 gene. It localizes to the centriole, and its S. pombe ortholog has been shown to be involved in spindle pole body duplication. SFI1 forms a complex with centrin 2.
Renata Homem de Gouveia Xavier de Basto is a researcher in cell and developmental biology. She is currently a team leader at the Institut Curie in Paris. She is also the deputy director of the CNRS research Unit UMR144 'Cell biology and cancer' at the Institut Curie which, comprises 14 research teams.