Black, Lindsay W. - University of Maryland-Baltimore - Department of Biochemistry and Molecular Biology

个人简介

Education B.S. - Biochemistry, The University of Chicago (Honors, Phi Beta Kappa) Ph.D. - Biochemistry, Department of Biochemistry, Stanford University School of Medicine Post Doctoral Fellow - Jane Coffin Childs Foundation- Institute of Molecular Biology, University of Geneva, Switzerland I was trained as a biochemist-molecular biologist as a graduate student in the laboratory of David Hogness, then working on lambda phage, in the biochemistry department of Arthur Kornberg in the Stanford Medical School; and then as a Jane Coffin Childs Fund Postdoctoral Fellow in the Institute of Molecular Biology, University of Geneva, Geneva, Switzerland in the laboratory of Eduard Kellenberger, a pioneering electron microscopist and structural biologist. I have maintained my interest in the prokaryotic problems I was introduced to in both of these eminent training centers. My research program has been supported for over 30 years by NIH. During this period I have received an NIH Merit Award.

研究领域

My primary interest is in viral nucleic acid packaging which is highly conserved. A powerful packaging motor is required to translocate DNA into an empty procapsid. The ATP powered phage motor consists of a packaging enzyme docked to a unique procapsid vertex containing a dodecameric portal. It packages DNA through the portal channel to ~500 mg/ml. We have shown that a long favored rotary portal motor mechanism does not apply (see reference #1 for recent review). Instead packaging in vitro of short dye labeled model DNA substrates provides evidence for a transient linear torsional B form to A form DNA "crunching" or spring-like motor mechanism to translocate DNA by the large terminase subunit (1, 3, 6, 9, 11, 12, 17) . A four strand "synapsis" of two homologous pac sequences in the DNA concatemer by a twin ring form of the small terminase subunit gauges DNA maturation and regulates cutting of the DNA by the large terminase to initiate packaging in vivo (1).

近期论文

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Black, L.W. (2015). Old, New, and Widely True: the Bacteriophage T4 DNA Packaging Mechanism. Review article for the 6oth Anniversary Special Issue of Virology, in press. liu JL, Dixit AB, Robertson KL, Qiao E, Black LW. 2014. Viral nanoparticle-encapsidated enzyme and restructured DNA for cell delivery and gene expression. Proc Natl Acad Sci U S A. 111:13319-24. Aparna Banerjee Dixit, Krishanu Ray, Julie A.Thomas, lindsay W. Black. 2013. The C-terminal domain of the bacteriophage T4 terminase docks on the prohead portal clip region during DNA packaging. Virology. 446, 293-302. Bubblegrams reveal the inner body of bacteriophage fKZ. Wu W, Thomas JA, Cheng N, Black LW, Steven AC. Science. 2012 Jan 13;335(6065):182. Condensed genome structure. Black LW, Thomas JA. Adv Exp Med Biol. 2012;726:469-87. Compression of the DNA substrate by a viral packaging motor is supported by removal of intercalating dye during translocation. Dixit AB, Ray K, Black LW. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20419-24. doi: 10.1073/pnas.1214318109. Epub 2012 Nov 26. PMID: 23185020 [PubMed - in process] Extensive proteolysis of head and inner body proteins by a morphogenetic protease in the giant Pseudomonas aeruginosa phage fKZ. Thomas JA, Weintraub ST, Wu W, Winkler DC, Cheng N, Steven AC, Black LW. Mol Microbiol. 2012 Apr;84(2):324-39. doi: 10.1111/j.1365-2958.2012.08025.x. Epub 2012 Mar 20. PMID: 22429790 [PubMed - indexed for MEDliNE] Bacteriophage T4 capsid packaging and unpackaging of DNA and proteins. Mullaney JM, Black LW. 2014. Methods Mol Biol 1108:69-85. doi: 10.1007/978-1-62703-751-8_5. Dynamics of the T4 bacteriophage DNA packasome motor: endonuclease VII resolvase release of arrested Y-DNA substrates. Dixit A, Ray K, Lakowicz JR, Black LW. J Biol Chem. 2011 May 27;286(21):18878-89. doi: 10.1074/jbc.M111.222828. Epub 2011 Mar 29. PMID: 21454482 [PubMed - indexed for MEDliNE] Free PMC Article Ray K, Ma J, Oram M, Lakowicz JR, Black LW. (2010) Single-molecule and FRET fluorescence correlation spectroscopy analyses of phage DNA packaging: colocalization of packaged phage T4 DNA ends within the capsid. J Mol Biol. 395(5):1102-13. (PMID: 19962991) Ray K, Sabanayagam CR, Lakowicz JR, Black LW. (2010) DNA crunching by a viral packaging motor: Compression of a procapsid-portal stalled Y-DNA substrate. Virology. 15:224-232. (PMID: 20060554) Ray K, Oram M, Ma J, Black LW. (2009) Portal control of viral prohead expansion and DNA packaging. Virology. 15: 391(1):44-50. (PMID: 19541336) Rifat D, Wright NT, Varney KM, Weber DJ, Black LW. (2008) Restriction endonuclease inhibitor IPI* of bacteriophage T4: a novel structure for a dedicated target. J Mol Biol. 375(3):720-34. (PMID: 18037438) Oram M, Sabanayagam C, Black LW. (2008) Modulation of the packaging reaction of bacteriophage T4 terminase by DNA structure. J Mol Biol. 381(1):61-72. (PMID: 18586272) Sabanayagam C, Oram M, Lakowicz JR, Black LW (2007) Viral DNA packaging studied by fluorescence correlation spectroscopy, Biophysical Journal, 93(4), 17-19. (PMID: 175557791) Bair CL, Black LW (2007) A Type IV modification dependent restriction nuclease that targets glucosylated hydroxymethyl cytosine modified DNAs. J Mol Biol. 366: 768. (PMID: 17188297) Baumann RG, Mullaney J, Black LW. (2006) Portal fusion protein constraints on function in DNA packaging of bacteriophage T4. Mol Microbiol. 61:16-32. (PMID: 16824092)