Trisha Davis

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Trisha Nell Davis (born May 27, 1954) is an American biochemist, the current Earl Davie/ZymoGenetics Chair of the department of biochemistry at the University of Washington. [1] Her early research focused on Calmodulin, though the primary focus of her lab has since shifted to the molecular machinery of cell division in budding yeast, especially the microtubule organizing centers and the kinetochores.

Contents

Background and education

Trisha Davis received her BA in Computer Science and Biology from the University of California, Santa Cruz in 1976. She received her Ph.D. in Molecular Biophysics and Biochemistry from Yale University in 1983. She joined the University of Washington Department of Biochemistry in 1997 and became acting chair of the department in 2011. In 2013, she became the first female chair of the Department.

Work and discoveries

Davis's post-doctoral research focused on Calmodulin in budding yeast [2] [3] After starting her own lab at the University of Washington, she discovered that Calmodulin performs an essential function in the yeast spindle pole body, [4] beginning the lab's gradual transition into the study of mitosis.

The Davis Lab has published extensively on the spindle pole body [5] [6] [7] [8] and on the kinetochore. [9] [10] [11] [12] Much of the recent research, conducted in collaboration with the Asbury Lab at the University of Washington, uses biophysical techniques such as optical tweezers to quantify the microtubule-coupling activity of the kinetochore.

Dr. Davis is also the director of the Yeast Resource Center (YRC), a Biomedical Technology Research Center supported by the National Institutes of Health and National Institute of General Medical Studies.

Awards and recognition

In 2020, Davis was named to the American Academy of Arts and Sciences. [13]

Related Research Articles

<span class="mw-page-title-main">Mitosis</span> Process in which replicated chromosomes are separated into two new identical nuclei

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.

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Spindle apparatus</span> Feature of biological cell structure

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 microtubule-organizing Centre (MTOC) is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell division. The MTOC is a major site of microtubule nucleation and can be visualized in cells by immunohistochemical detection of γ-tubulin. The morphological characteristics of MTOCs vary between the different phyla and kingdoms. In animals, the two most important types of MTOCs are 1) the basal bodies associated with cilia and flagella and 2) the centrosome associated with spindle formation.

<span class="mw-page-title-main">Karyogamy</span> Fusion of the nuclei of two haploid eukaryotic cells

Karyogamy is the final step in the process of fusing together two haploid eukaryotic cells, and refers specifically to the fusion of the two nuclei. Before karyogamy, each haploid cell has one complete copy of the organism's genome. In order for karyogamy to occur, the cell membrane and cytoplasm of each cell must fuse with the other in a process known as plasmogamy. Once within the joined cell membrane, the nuclei are referred to as pronuclei. Once the cell membranes, cytoplasm, and pronuclei fuse, the resulting single cell is diploid, containing two copies of the genome. This diploid cell, called a zygote or zygospore can then enter meiosis, or continue to divide by mitosis. Mammalian fertilization uses a comparable process to combine haploid sperm and egg cells (gametes) to create a diploid fertilized egg.

<span class="mw-page-title-main">Spindle checkpoint</span> Cell cycle checkpoint

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 metaphase of 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.

<span class="mw-page-title-main">Kinetochore</span> Protein complex that allows microtubules to attach to chromosomes during cell division

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

Monopolin is a protein complex that in budding yeast is composed of the four proteins CSM1, HRR25, LRS4, and MAM1. Monopolin is required for the segregation of homologous centromeres to opposite poles of a dividing cell during anaphase I of meiosis. This occurs by bridging DSN1 kinetochore proteins to sister kinetochores within the centromere to physically fuse them and allow for the microtubules to pull each homolog toward opposite mitotic spindles.

<span class="mw-page-title-main">Motor protein</span> Class of molecular proteins

Motor proteins are a class of molecular motors that can move along the cytoplasm of cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump.

<span class="mw-page-title-main">Aurora kinase B</span> Protein

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.

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

Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).

<span class="mw-page-title-main">NUF2</span> Protein-coding gene in the species Homo sapiens

Kinetochore protein Nuf2 is a protein that in humans is encoded by the NUF2 gene.

Iain Cheeseman investigates the role of the kinetochore, a group of proteins required for cell division and chromosome segregation. This core network of proteins facilitates the attachment of chromosomes to microtubule polymers—the spindle structures that attach to the ends of cells, pulling and dividing them during cell division. The kinetochore is critical to ensuring duplication without loss or damage to the genetic material. Cheeseman is also investigating the activities of the individual molecular machines that make up this structure and how these proteins are controlled and regulated.

Syntelic attachment occurs when both sister chromosomes are attached to a single spindle pole.

<span class="mw-page-title-main">Mad1</span>

Mad1 is a non-essential protein which in yeast has a function in the spindle assembly checkpoint (SAC). This checkpoint monitors chromosome attachment to spindle microtubules and prevents cells from starting anaphase until the spindle is built up. The name Mad refers to the observation that mutant cells are mitotic arrest deficient (MAD) during microtubule depolymerization. Mad1 recruits the anaphase inhibitor Mad2 to unattached kinetochores and is essential for Mad2-Cdc20 complex formation in vivo but not in vitro. In vivo, Mad1 acts as a competitive inhibitor of the Mad2-Cdc20 complex. Mad1 is phosphorylated by Mps1 which then leads together with other activities to the formation of the mitotic checkpoint complex (MCC). Thereby it inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C). Homologues of Mad1 are conserved in eukaryotes from yeast to mammals.

Biorientation is the phenomenon whereby microtubules emanating from different microtubule organizing centres (MTOCs) attach to kinetochores of sister chromatids. This results in the sister chromatids moving to opposite poles of the cell during cell division, and thus results in both daughter cells having the same genetic information.

The XMAP215/Dis1 family is a highly conserved group of microtubule-associated proteins (MAPs) in eukaryotic organisms. These proteins are unique MAPs because they primarily interact with the growing-end (plus-end) of microtubules. This special property classifies this protein family as plus-end tracking proteins (+TIPs).

<span class="mw-page-title-main">Andrea Musacchio</span> Italian biologist

Andrea Musacchio is an Italian structural biologist. He is Max Planck director at the Institute of Molecular Physiology in Dortmund. He is also Honorary Professor at the Center for Medical Biotechnology at the University of Duisburg-Essen. He was named European Molecular Biology Organization member in 2009.

<span class="mw-page-title-main">Iva Tolić</span> Croatian agricultural biologist

Iva Marija Tolić is a Croatian biophysicist, known for her work on the microtubule cytoskeleton and associated motor proteins. She is currently Senior Research Group Leader and professor of Biology at the Ruđer Bošković Institute in Zagreb, Croatia.

J. Richard McIntosh is a Distinguished Professor Emeritus in Molecular, Cellular, and Developmental Biology at the University of Colorado Boulder. McIntosh first graduated from Harvard with a BA in Physics in 1961, and again with a Ph.D. in Biophysics in 1968. He began his teaching career at Harvard but has spent most of his career at the University of Colorado Boulder. At the University of Colorado Boulder, McIntosh taught biology courses at both the undergraduate and graduate levels. Additionally, he created an undergraduate course in the biology of cancer towards the last several years of his teaching career. McIntosh's research career looks at a variety of things, including different parts of mitosis, microtubules, and motor proteins.

References

  1. ↑ Advancement, UW Medicine. "Trisha N. Davis, Ph.D. - UW Medicine". Chairs & Professorships. Retrieved 2020-05-12.
  2. ↑ Davis, Trisha N.; Urdea, Mickey S.; Masiarz, Frank R.; Thorner, Jeremy (1986). "Isolation of the yeast calmodulin gene: Calmodulin is an essential protein". Cell. 47 (3): 423–431. doi:10.1016/0092-8674(86)90599-4. ISSN   0092-8674. PMID   3533275. S2CID   40739181.
  3. ↑ Davis, T. N.; Thorner, J. (1989). "Vertebrate and yeast calmodulin, despite significant sequence divergence, are functionally interchangeable". Proceedings of the National Academy of Sciences. 86 (20): 7909–7913. Bibcode:1989PNAS...86.7909D. doi: 10.1073/pnas.86.20.7909 . ISSN   0027-8424. PMC   298181 . PMID   2554295.
  4. ↑ Moser, M.J.; Flory, M.R.; Davis, T.N. (1997-08-01). "Calmodulin localizes to the spindle pole body of Schizosaccharomyces pombe and performs an essential function in chromosome segregation". Journal of Cell Science. 110 (15): 1805–1812. doi:10.1242/jcs.110.15.1805. ISSN   0021-9533. PMID   9264467 . Retrieved 2020-05-12.
  5. ↑ Fong, Kimberly K.; Zelter, Alex; Graczyk, Beth; Hoyt, Jill M.; Riffle, Michael; Johnson, Richard; MacCoss, Michael J.; Davis, Trisha N. (2018-06-14). "Novel phosphorylation states of the yeast spindle pole body". Biology Open. The Company of Biologists. 7 (10): bio033647. doi: 10.1242/bio.033647 . ISSN   2046-6390. PMC   6215409 . PMID   29903865.
  6. ↑ Viswanath, Shruthi; Bonomi, Massimiliano; Kim, Seung Joong; Klenchin, Vadim A.; Taylor, Keenan C.; Yabut, King C.; Umbreit, Neil T.; Van Epps, Heather A.; Meehl, Janet; Jones, Michele H.; Russel, Daniel; Velazquez-Muriel, Javier A.; Winey, Mark; Rayment, Ivan; Davis, Trisha N.; Sali, Andrej; Muller, Eric G. (2017-11-07). Bloom, Kerry S. (ed.). "The molecular architecture of the yeast spindle pole body core determined by Bayesian integrative modeling". Molecular Biology of the Cell. American Society for Cell Biology (ASCB). 28 (23): 3298–3314. doi: 10.1091/mbc.e17-06-0397 . ISSN   1059-1524. PMC   5687031 . PMID   28814505.
  7. ↑ Fong, Kimberly K.; Sarangapani, Krishna K.; Yusko, Erik C.; Riffle, Michael; Llauró, Aida; Graczyk, Beth; Davis, Trisha N.; Asbury, Charles L. (2017-07-07). Bloom, Kerry S. (ed.). "Direct measurement of the strength of microtubule attachment to yeast centrosomes". Molecular Biology of the Cell. American Society for Cell Biology (ASCB). 28 (14): 1853–1861. doi: 10.1091/mbc.e17-01-0034 . ISSN   1059-1524. PMC   5541836 . PMID   28331072.
  8. ↑ Lyon, Andrew S.; Morin, Geneviève; Moritz, Michelle; Yabut, King Clyde B.; Vojnar, Tamira; Zelter, Alex; Muller, Eric; Davis, Trisha N.; Agard, David A. (2016-07-15). Doxsey, Stephen (ed.). "Higher-order oligomerization of Spc110p drives γ-tubulin ring complex assembly". Molecular Biology of the Cell. American Society for Cell Biology (ASCB). 27 (14): 2245–2258. doi: 10.1091/mbc.e16-02-0072 . ISSN   1059-1524. PMC   4945142 . PMID   27226487.
  9. ↑ Scarborough, Emily Anne; Davis, Trisha N; Asbury, Charles L (2019-05-02). "Tight bending of the Ndc80 complex provides intrinsic regulation of its binding to microtubules". eLife. eLife Sciences Publications, Ltd. 8. doi: 10.7554/elife.44489 . ISSN   2050-084X. PMC   6516834 . PMID   31045495.
  10. ↑ Kim, Jae ook; Zelter, Alex; Umbreit, Neil T; Bollozos, Athena; Riffle, Michael; Johnson, Richard; MacCoss, Michael J; Asbury, Charles L; Davis, Trisha N (2017-02-13). "The Ndc80 complex bridges two Dam1 complex rings". eLife. eLife Sciences Publications, Ltd. 6. doi: 10.7554/elife.21069 . ISSN   2050-084X. PMC   5354518 . PMID   28191870.
  11. ↑ Zelter, Alex; Bonomi, Massimiliano; Kim, Jae ook; Umbreit, Neil T.; Hoopmann, Michael R.; Johnson, Richard; Riffle, Michael; Jaschob, Daniel; MacCoss, Michael J.; Moritz, Robert L.; Davis, Trisha N. (2015-11-12). "The molecular architecture of the Dam1 kinetochore complex is defined by cross-linking based structural modelling". Nature Communications. Springer Science and Business Media LLC. 6 (1): 8673. Bibcode:2015NatCo...6.8673Z. doi: 10.1038/ncomms9673 . ISSN   2041-1723. PMC   4660060 . PMID   26560693.
  12. ↑ Powers, Andrew F.; Franck, Andrew D.; Gestaut, Daniel R.; Cooper, Jeremy; Gracyzk, Beth; Wei, Ronnie R.; Wordeman, Linda; Davis, Trisha N.; Asbury, Charles L. (2009). "The Ndc80 Kinetochore Complex Forms Load-Bearing Attachments to Dynamic Microtubule Tips via Biased Diffusion". Cell. Elsevier BV. 136 (5): 865–875. doi:10.1016/j.cell.2008.12.045. ISSN   0092-8674. PMC   2749323 . PMID   19269365.
  13. ↑ "UW president, biochemistry chair and mathematics professor named to American Academy of Arts and Sciences". UW News. 2020-04-23. Retrieved 2020-05-12.
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