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This is an old revision of this page, as edited by LLMHoopes (talk | contribs) at 01:13, 23 August 2018 (copyediting for clarity. Still confusing in part, more copyediting is needed.). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

I am drafting improvements to the existing stub. They will be transferred to the live page after review, keeping the infobox and the photograph as is. Input welcomed (on talk page for this sandbox). Thank you, LH

PS it's ok with me if you write some of your comments on this page and the overview on the talk page, or you can put it all on the talk page if you prefer. LH

Mary Osborn (born in 1940)[1] is a L'Oréal-UNESCO Women in Science Award-winning English cell biologist who, until she stopped running an active laboratory in 2005,[2] was on the scientific staff at the Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.[2] Osborn established two techniques frequently used by cell biologists. She pioneered both molecular weight determination of proteins using SDS PAGE[3] and immunofluorescence microscopy.[4] Osborn also used the immunofluorescence microscopy method to work out the details of the eukaryotic cytoskeleton. Small differences in the intermediate filament constituents helped her distinguish differentiated cells from each other[5] as well as normal versus cancer cells.[5] Mary Osborn has been a prominent spokesperson for women in science.[6]

Early Life and Education

Osborn was born in Darlington, UK[1] on December 16, 1940.[7] Osborn completed high school education at Cheltenham Ladies' College and university education at Newnham College, Cambridge University where she was graduated in Mathematics and Physics in 1962.[1] She received a masters in biophysics at Pennsylvania State University in 1963 . Her PhD on mutagenesis in nonsense mutations in bacteria was awarded by Pennsylvania State University in 1972.[2]

Research career

Mary Osborn carried out postdoctoral research from 1967-69 in the laboratory of James Watson at Harvard University.[2] Then she conducted research at the Laboratory of Molecular Biology, Cambridge, UK (1969-72) before moving to the Cold Spring Harbor Laboratory (1972-75.)[1] Osborn had married her husband, Klaus Weber, on July 14, 1972.[7] Weber and Osborn moved to the Göttingen Max Planck Institute for Biophysical Chemistry where Weber was Director and Osborn received a staff appointment in 1975.[1] in 1989, she was appointed an honorary professor at University of Göttingen.[2]

Mary Osborn and Klaus Weber wrote a classic paper in biochemistry on determination of the molecular weight of a protein via SDS polyacrylamide gel electrophoresis, published in 1969 in Journal of Biological Chemistry.[8][3] They knew that in 1967 Shapiro, Vinuela, and Maisel had shown that electrophoresis of proteins along with Sodium Dodecyl Sulfate (SDS) in polyacrylamide gels (PAGE) could separate the tested polypeptide chains by molecular weight.[9] To see if this method applied to proteins of various sizes and shapes, Osborn and Weber took 40 known proteins, including globular and filamentous proteins, analyzed them via SDS PAGE, and plotted the logarithms of their molecular weights against their electrophoretic mobilities.[8] The results showed convincingly that “the good resolution and the fact that an estimate of the molecular weight can be obtained within a day, together with the small amount of protein needed, makes the method strongly competitive with others commonly employed.”[3] This method has been used extensively by biochemists in all kinds of studies involving protein purification and identification as part of the process.

Later, Osborn and Weber pioneered fluorescent antibody staining of cellular substructures, a major technique called indirect immunofluorescence microscopy.[6] In developing the method, they tagged microtubules with specific antibodies, then used fluorescently-tagged secondary antibodies (antibodies to the first set of antibodies) to light up the locations of the microtubules in cells.[8] When they began their work in Germany, the cytoskeleton was not heavily researched. Microtubules and microfilaments were known, and they established that microtubules always reacted with antibodies to tubulins while microfilaments always reacted with antibodies to actin. In the course of their studies, they also found intermediate filaments, slightly thicker than microfilaments, and unreactive to actin antibodies.[4][10] They developed new antibodies against proteins of the microtubules, intermediate filaments, and microfilaments to use as reagents in examining many types of cells.[5] Many of their antibodies have been licensed to companies for commercial development.[11] Klaus and Osborn used their method to study elements of the cytoskeleton of eukaryotic cells in two dimensions and three dimensions.[4] Osborn has extensively studied microtubules, intermediate filaments, microfilaments, and nuclear proteins as well as other proteins that can associate with these structures. By 1981 Osborn and Klaus had shown conclusively intermediate filaments in different types of cells are different but related, and they can be distinguished using immunofluorescence.[12] Soon thereafter, in 1982, the laboratory showed that many tumors differ from their matching normal tissue in the protein details of intermediate filaments as shown by immunofluorescence.[12] [13] They also found that intermediate filament composition was tumor-specific.[5][13] Osborn and Weber have pioneered the diagnostic classification of tumor types using specific cytoskeletal elements determined via immunofluorescence microscopy. Their methods have been widely applied in numerous clinical studies of muscular dystrophy and cancer. [6]

Support of Women Scientists

When Mary Osborn returned to Europe after years in the USA, she was surprised to find that European science, technology, engineering, and mathematics (STEM fields) had not opened doors to women as she had experienced in America. She was quoted in an article in Science in 1994 to the effect that women's role in Germany was still "kinder, kuche, kirch" (children, kitchen, church.)[14] In 1992, she had written a protest letter in response to an editorial in Nature that had claimed child care issues were chiefly responsible for the leaky pipeline for women in science, not discrimination.[6][8] As a woman without children who had experienced no gender discrimination early in her career but had seen differential treatment of men and women in science later, she did not find this argument convincing, and she was appalled to find out that Europe had collected little or no data on rates of success of women in science. Partly because Osborn objected to this situation, the European Commission (EC) appointed her co-chair of a working group to investigate the status of European women scientists and scientists in training and in employment and to prepare a report.[6] The outcome was the European Technology Assessment Network (ETAN) Report on Women in Science, published in 2006, which identified a number of reasons why women dropped out of science and served as a blueprint for Europeans who wished to fix this problem.[6][8] She noted in 2012 that there was still a leaky pipeline for women scientists in Germany..[5] She has given a great deal of thought to how women are taught to act as they grow up and how that may impact their career decisions. In an interview in 2004, Osborn said, "In deciding whether to accept new challenges a remark by Diane Britten some years ago in The Times has proved very helpful: “When asked to do something women tend to say `Why me?' Men say `Why not me?' I have learned to say `Why not me?'''[1] Summing up her advice to those in charge of sciences in universities and industry, she said in 2012, "Above all one has to get the argument across that it is wasteful, expensive and unfair to educate and train large numbers of female scientists and then not use their talents in the job market or provide equal access to the top jobs."[5]

Awards and honors[15]

  • 1979 Elected member, European Molecular Biology Organisation
  • 1987 Meyenburg Prize for Cancer Research
  • 1995 Elected member, Academia Europaea
  • 1997 Doctorate honoris causa, Pomeranian Medical Academy, Szczecin, Poland
  • 1998 Carl Zeiss Prize, German Society of Cell Biology, (shared with Klaus Weber)
  • 1998 Helena Rubenstein / UNESCO Prize for Women in Science (UK)
  • 2002 L'Oréal / UNESCO Prize for Women in Science
  • 2005 Outstanding Science Alumni Award, Pennsylvania State University, USA
  • 2014. Federal Cross of Merit, 1st Class, Federal Republic of Germany [16]
  • 2007 Dorothea Schlözer Medal, University of Göttingen, Germany

References

  1. ^ a b c d e f F. M. Watt. (2004) "Mary Osborn" Journal of Cell Science 117(8):1255-1256.
  2. ^ a b c d e Osborn, Mary (2018). "Mary Osborn". Goettingen Max Planck Institute for Biophysical Chemistry. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  3. ^ a b c Klaus Weber and Mary Osborn. (1969) "The Reliability of Molecular Weight Determinations by Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis" Journal of Biological Chemistry 213 (16): 4406-4412.
  4. ^ a b c Mary Osborn, Werner Franke, and Klaus Weber, (1977) "Visualization of a system of filaments 7-10nm thick in cultured cells of an epithelioid line (Pt K2) by immunofluorescence microscopy" Proceedings of the National Academy of Sciences 74 (6):2490-2494.
  5. ^ a b c d e f “Genome Biology: Women in Science.” (2012) Genome Biology 13: 148-154. doi:10.1186/gb-2012-13-3-148.
  6. ^ a b c d e f Silvia Sanides. (2004) "Cell Biologist Multitasks for Women" The Scientist, March 15.
  7. ^ a b Osborn, Mary (2018). "Mary Osborn". Prabook. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  8. ^ a b c d e Nicole Kresge, Robert Simoni, and Robert Hill. (2006) "Classics. A paper in a series reprinted to celebrate the centennial of the JBC in 2005. SDS PAGE to determine the molecular weight of proteins: the work of Klaus Weber and Mary Osborn." Journal of Biological Chemistry 281 (24): e19.
  9. ^ AL Shapiro, E. Vinuela, and JV Maizel., Jr. (1967) "Molecular weight estimation of polypeptide chains by electrophoresis in SDS-polyacrylamide gels." Biochem. Biophys. Res. Commun. 28: 815–820,
  10. ^ "Scientific American Stories by Mary Osborn". Retrieved August 10, 2018. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  11. ^ "UNESCO: Mary Osborn". UNESCO. 2004. Retrieved August 7, 2018. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  12. ^ a b M. Altmannsberger, M. Osborn,  A. Schauer, and K. Weber. (1981) “Antibodies to different intermediate filament proteins, cell type-specific markers on paraffin- embedded human tissues.” Lab. Invest. 45, 427-434.
  13. ^ a b M. Altmannsberger, M. Osborn, K. Weber, and A. Schauer. (1982) “Expression of intermediate filaments in different human epithelial and mesenchymal tumors.” Path. Res. Pract. 175, 227-237.
  14. ^ Peter Aldhous, (1994) “News: Germany. The Backbreaking Work of Scientist Homemakers.” Science263 (5152):1475-1480.
  15. ^ Academia Net (2018). "Mary Osborn". Academia Net. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  16. ^ "Max Planck Institute at Gottingen, Germany". Osborn Curriculum Vitae. Retrieved August 7, 2018. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)

Regulatory RNAs

Regulatory RNAs

(*******This is a separate article; it's from "RNA" and I'm trying to make it more comprehensive and up to date. Do not read if you are giving input on Mary Osborn.)

Several types of RNA can regulate gene expression. MicroRNAs and small interferingRNAs control at the level of translation of protein by affecting the stability or the binding ability of messenger RNA. The long non-coding RNAs (lncRNAs) act to compact large regions of chromatin. The enhancer RNAs control one or a few genes by regulating transcription of messenger RNA from the enhancer-controlled gene(s). The bacterial small RNAs act during translation but can either up or down regulate expression. Riboswitches, allosterically controlled shapes of mRNA itself, can also either up or down regulate expression. CRISPR, a prokaryotic defense mechanism, uses RNA control to stop gene expression.

Small eukaryotic RNAs act by being complementary to a part of an mRNA or a gene's DNA.[1][2] MicroRNAs (miRNA; 21–22 nt) are found in eukaryotes and act through RNA interference (RNAi), where an effector complex of miRNA and enzymes can cleave complementary mRNA, block the mRNA from being translated, or accelerate its degradation.[3][4]

The small interfering RNAs (siRNA; 20–25 nt) are often produced by breakdown of viral RNA, but there are also endogenous sources of siRNAs.[5][6] The siRNAs act through RNA interference in a fashion similar to miRNAs. Alternatively, instead of translational control, some miRNAs and siRNAs can cause genes they target to be methylated, thereby decreasing or increasing transcription of those genes.[7][8][9] A special system acting through siRNA uses Piwi-interacting RNAs (piRNA; 29–30 nt). The piRNA systems play a role in forming eggs and sperm; they are active in germline cells and are thought to be a defense against transposons.[10][11]

Bacterial small RNA regulates the translation of prokaryote mRNAs. That type of system is similar to the eukaryotes' RNA interference system but can have either up- or down-regulatory effects on the genes it targets.

Many prokaryotes have CRISPR RNAs, an RNA-dependent system that provides protection against viruses for bacteria and Archaea.[12] Antisense RNAs are used to target genes in the CRISPR system but other uses of these RNAs are widespread. Most downregulate a gene, but a few are activators of transcription.[13] One way antisense RNA can act is by binding to an mRNA, forming double-stranded RNA that is enzymatically degraded.[14]

A messenger RNA may contain regulatory elements itself, such as riboswitches, in the 5' untranslated region or 3' untranslated region; these cis-regulatory elements allosterically bind to metabolites to regulate the stability or accessibility of binding sites of that mRNA.[15] The untranslated regions can also contain elements that regulate other genes.[16]

There are many eukaryotic long noncoding RNAs (lncRNAs) that down regulate blocks of adjacent genes.[17][18] A major group of such lncRNAs controls X chromosome inactivation in mammals, for example Xist, which coats one X chromosome in female mammals and inactivates it.[19] Shutting down of large blocks of chromatin during X-inacdtivation involves the epigenetic process of Polycomb-protein-induced condensation.[20]

Another type of regulatory RNA is enhancer RNA, transcribed from enhancers which are regions in the DNA that control a gene or genes.[18] The enhancer RNAs are transcribed from the enhancer and up- or down-regulate expression of the genes that the enhancer controls.[21]

  1. ^ Carthew RW, Sontheimer EJ (February 2009). "Origins and Mechanisms of miRNAs and siRNAs". Cell. 136 (4): 642–55. doi:10.1016/j.cell.2009.01.035. PMC 2675692. PMID 19239886.
  2. ^ Liang KH, Yeh CT (May 2013). "A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs". BMC Genomics. 14: 325. doi:10.1186/1471-2164-14-325. PMC 3655826. PMID 23663499.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ Wu L, Belasco JG (January 2008). "Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs". Molecular Cell. 29 (1): 1–7. doi:10.1016/j.molcel.2007.12.010. PMID 18206964.
  4. ^ Matzke MA, Matzke AJ (May 2004). "Planting the seeds of a new paradigm". PLoS Biology. 2 (5): E133. doi:10.1371/journal.pbio.0020133. PMC 406394. PMID 15138502.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  5. ^ Vazquez F, Vaucheret H, Rajagopalan R, Lepers C, Gasciolli V, Mallory AC, Hilbert JL, Bartel DP, Crété P (October 2004). "Endogenous trans-acting siRNAs regulate the accumulation of Arabidopsis mRNAs". Molecular Cell. 16 (1): 69–79. doi:10.1016/j.molcel.2004.09.028. PMID 15469823.
  6. ^ Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, Chiba H, Kohara Y, Kono T, Nakano T, Surani MA, Sakaki Y, Sasaki H (May 2008). "Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes". Nature. 453 (7194): 539–43. Bibcode:2008Natur.453..539W. doi:10.1038/nature06908. PMID 18404146. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  7. ^ Sontheimer EJ, Carthew RW (July 2005). "Silence from within: endogenous siRNAs and miRNAs". Cell. 122 (1): 9–12. doi:10.1016/j.cell.2005.06.030. PMID 16009127.
  8. ^ Doran G (2007). "RNAi – Is one suffix sufficient?". Journal of RNAi and Gene Silencing. 3 (1): 217–19. Archived from the original on 2007-07-16. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  9. ^ Pushparaj PN, Aarthi JJ, Kumar SD, Manikandan J (January 2008). "RNAi and RNAa--the yin and yang of RNAome". Bioinformation. 2 (6): 235–7. doi:10.6026/97320630002235. PMC 2258431. PMID 18317570.
  10. ^ Horwich MD, Li C, Matranga C, Vagin V, Farley G, Wang P, Zamore PD (July 2007). "The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC". Current Biology. 17 (14): 1265–72. doi:10.1016/j.cub.2007.06.030. PMID 17604629.
  11. ^ Girard A, Sachidanandam R, Hannon GJ, Carmell MA (July 2006). "A germline-specific class of small RNAs binds mammalian Piwi proteins". Nature. 442 (7099): 199–202. Bibcode:2006Natur.442..199G. doi:10.1038/nature04917. PMID 16751776.
  12. ^ Horvath P, Barrangou R (January 2010). "CRISPR/Cas, the immune system of bacteria and archaea". Science. 327 (5962): 167–70. Bibcode:2010Sci...327..167H. doi:10.1126/science.1179555. PMID 20056882.
  13. ^ Wagner EG, Altuvia S, Romby P (2002). "Antisense RNAs in bacteria and their genetic elements". Advances in Genetics. Advances in Genetics. 46: 361–98. doi:10.1016/S0065-2660(02)46013-0. ISBN 9780120176465. PMID 11931231.
  14. ^ Developmental Biology (7th ed.). Sinauer. 2003. pp. 101–3. ISBN 0-87893-258-5. OCLC 154656422. {{cite book}}: Unknown parameter |authors= ignored (help)
  15. ^ Batey RT (June 2006). "Structures of regulatory elements in mRNAs". Current Opinion in Structural Biology. 16 (3): 299–306. doi:10.1016/j.sbi.2006.05.001. PMID 16707260.
  16. ^ Scotto L, Assoian RK (June 1993). "A GC-rich domain with bifunctional effects on mRNA and protein levels: implications for control of transforming growth factor beta 1 expression". Molecular and Cellular Biology. 13 (6): 3588–97. PMC 359828. PMID 8497272.
  17. ^ Amaral PP, Mattick JS (August 2008). "Noncoding RNA in development". Mammalian Genome. 19 (7–8): 454–92. doi:10.1007/s00335-008-9136-7. PMID 18839252.
  18. ^ a b John L. Rinn and Howard Y. Chang.  (2012) “Genome regulation by long noncoding RNAs” Ann. Rev. Biochem 81:1-25. doi: 10.1146/annurev-biochem-051410-092902
  19. ^ Heard E, Mongelard F, Arnaud D, Chureau C, Vourc'h C, Avner P (June 1999). "Human XIST yeast artificial chromosome transgenes show partial X inactivation center function in mouse embryonic stem cells". Proceedings of the National Academy of Sciences of the United States of America. 96 (12): 6841–6. Bibcode:1999PNAS...96.6841H. doi:10.1073/pnas.96.12.6841. PMC 22003. PMID 10359800.
  20. ^ J Zhao, BK Sun, JA Erwin, JJ Song, and JT Lee. (2008) “Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.” Science 322:750–6. [PubMed: 18974356]
  21. ^ UA Orom, T Derrien, M Beringer, K Gumireddy, A. Gardini, et al.(2010) ‘Long noncoding RNAs with enhancer-like function in human cells.” Cell 143:46–58. [PubMed: 20887892]
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