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Jay Clark Brown

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Jay Clark Brown
NationalityAmerican
Occupation(s)Molecular biologist, microbiologist, virologist, and academic
Academic background
EducationB.Sc. in Biology
PhD in Biochemistry
Alma materJohns Hopkins University
Harvard University
MRC Laboratory of Molecular Biology
Thesis (1969)
Academic work
InstitutionsUniversity of Virginia

Jay Clark Brown is an American molecular biologist, microbiologist, virologist, and academic. He is a Professor Emeritus in the Department of microbiology, immunology, and cancer biology at the University of Virginia School of Medicine.[1]

Brown is most known for his work in the field of molecular biology, computational biology, genomics, structural biology, and microbiology with a particular focus on the structure and assembly of herpes simplex virus,[2] human papilloma virus[3] and Human gene expression.[4] He is the co-author of two books including, Medical Cell Biology and Basic Microbiology.

Brown is an Academic Editor of Advances in Virology.[5]

Education

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Brown enrolled at Johns Hopkins University, in 1964, and graduated with a BSc in biology. He then undertook research in the area of Biochemistry and Molecular Biology at Harvard University, and earned his Ph.D. in 1969, under the mentorship of Paul M. Doty. Following the completion of his Ph.D., he received a post-doctoral NATO fellowship in molecular biology and joined the MRC Laboratory of Molecular Biology at Cambridge, where he worked under the supervision of Francis Crick.[1]

Career

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After completing his post-doc in 1971, Brown joined the Department of Microbiology in the School of Medicine at the University of Virginia as Assistant Professor and ascended through the ranks to Professor in 1987. During the summers between 1977 and 1980 he also held an appointment at the Marine Biological Laboratory at Woods Hole, Massachusetts, where he taught Physiology. He is currently a Professor Emeritus of microbiology, immunology, and cancer biology at University of Virginia School of Medicine.[6]

He held appointments as a vice-chair in 1998 and a chair in 1999, under the cancer study section at the American Cancer Society.[1]

Research

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Brown's research primarily focuses on the areas of molecular biology and microbiology. At the beginning of his career, he explored several aspects of molecular biology, with a particular focus on the genetic code. Later his work was aimed at understanding the fundamentals of microbiology and virology and several aspects related to it. Thereafter, he and his team began to work on the structural and functional properties of herpes simplex virus. More recently, he has branched out into human gene expression.[7]

Brown's current research revolves around the control of human gene expression and Organization of transcription factor binding sites in the promoters of human genes. He has co-written more than 100 peer-reviewed articles for leading journals and has been cited broadly throughout his career.[8]

Molecular Biology

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Brown began his work in molecular biology with a substantial interest in the genetic code. During his PhD, under the supervision of Paul Doty, he proposed the development of new methods to synthesize oligonucleotides of defined sequence and studied their coding properties.[9] Subsequently, he demonstrated that the incorporation of N-formylmethionine is stimulated by oligonucleotide messengers that contain the sequence AUG near or at the 5’ end of the messenger RNA chain and that it does not stimulate unformulated methionine.[10] He further revealed that AUG is capable of encoding methionine for both initiating and extension methionines.[11]

Following that Brown has worked on the surface glycoproteins and revealed a cell surface glycoprotein characterized as a differentiated state of neuroblastoma C-1300 cells.[12] In his research, he has elucidated significant differences in the amounts of 4 glycopeptide classes extracted from vertebrate cells and also detected a glycopeptide which was only present during the cell-division period and named it glycol-peptide 4.[13] He also identified differential properties of cell surface membrane from the internal membrane, and particularly highlighted that the isolation of glycoproteins with smooth membrane fraction of cell homogenates characterizes them from internal glycoproteins. Based on these criteria, he isolated two molecular weight classes of glycoproteins as the constituents of the plasma membrane of mouse L-929 cells[14] and suggested that band 1 polypeptide might be efficiently involved in regulating L cell growth.[15]

More recently, Brown has augmented his research expertise in analyzing gene expression. He compared the effect of promoters in genes strongly expressed in all tissues with genes that were expressed in a restricted set of tissues and identified the involvement of Polycomb Repressive Complex 2 genes of tissue-targeted transcription factor genes in the repression of transcription factor gene expression.[16] Whilst working on gene expression, he proposed that for the protection of promoter's ability to regulate gene expression from the mutagenic damage the transcription binding sites of promoters are arrayed in multiple forms and ascertained supportive evidence in brain and liver-specific gene expression.[17]

Microbiology

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Brown has worked widely on vesicular stomatitis virus, herpes simplex virus, and human papilloma virus. His research justified the view that the vesicular stomatitis virus matrix M (VSV-M) protein plays a vital role in the maintenance of nucleocapsid in a compact form[18] and mentioned the possibility of identical functionality of VSV-M in-vivo.[19] While working on the physical characteristics of N protein of vesicular stomatitis virus through electron microscopy images he inferred that the N protein has a bilobed structure and is wedge-shaped with an approximate 9.0 nm, 5.0 nm, and 3.3 nm of length, depth, and width respectively.[20] In 1991, he started working on Human papilloma virus and published its structure using cryoelectron microscopy. His work clarified that the structural capsid hexon of the human papilloma virus is molecular pentameres.[21]

A major part of Brown's work was on herpes simplex virus (HSV) and mainly focuses on its structure[2] and assembly to determine properties that can aid in the development of novel anti-herpes therapeutic drugs. He illustrated the molecular composition of the capsid pentons and the triplexes of HSV 1 using the guanidine-HCl extraction[22] and discovered that the protein of abortive capsids of equine herpes virus is entirely encapsulated within the capsid.[23] Later, he detected that the HSV capsid assembles in a cell-free environment with the help of four capsid proteins, including VP5 as the major capsid protein, VP22a as a scaffolding protein and VP19c and VP23 as triplex proteins.[24] In related research, he discovered that a mature, icosahedral herpes simplex virus capsid is formed by a spherical intermediate named procapsid,[25] studied the maturation of procapsid through cryoelectron microscopy[26] and described the distinct structural and conformational changes that occur when a procapsid and is transformed into a mature one.[27] Furthermore, he identified the portal that allows entry and exit of herpes virus DNA from the capsid, at the capsid vertex and also demonstrated the isolation of intact capsid from insect cells that produce pUL6 protein.[28]

Bibliography

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Books

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  • Basic Microbiology (1997) ISBN 978-0673995605
  • Medical Cell Biology (1979) ISBN 978-0721637211

Selected articles

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  • Brown, J. C., Newcomb, W. W., & Lawrenz-Smith, S. (1988). pH-dependent accumulation of the vesicular stomatitis virus glycoprotein at the ends of intact virions. Virology, 167(2), 625–629.
  • Homa, F. L., & Brown, J. C. (1997). Capsid assembly and DNA packaging in herpes simplex virus. Reviews in medical virology, 7(2), 107–122.
  • Copeland, A. M., Newcomb, W. W., & Brown, J. C. (2009). Herpes simplex virus replication: roles of viral proteins and nucleoporins in capsid-nucleus attachment. Journal of virology, 83(4), 1660–1668.
  • Brown, J. C. (2021). Role of gene length in control of human gene expression: chromosome-specific and tissue-specific effects. International journal of genomics, 2021.
  • Brown, J. C. (2022). Control of Expression Level in Human Genes: Observations with Apoptosis Genes and Genes Involved in B cell Development. Journal of Bioinformatics and Systems Biology, 5, 108–115.

References

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  1. ^ a b c "Brown, Jay C."
  2. ^ a b Newcomb, William W.; Trus, Benes L.; Booy, Frank P.; Steven, Alasdair C.; Wall, Joseph S.; Brown, Jay C. (July 20, 1993). "Structure of the Herpes Simplex Virus Capsid Molecular Composition of the Pentons and the Triplexes". Journal of Molecular Biology. 232 (2): 499–511. doi:10.1006/jmbi.1993.1406. PMID 8393939 – via ScienceDirect.
  3. ^ Baker, T. S.; Newcomb, W. W.; Olson, N. H.; Cowsert, L. M.; Olson, C.; Brown, J. C. (December 1, 1991). "Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction". Biophysical Journal. 60 (6): 1445–1456. Bibcode:1991BpJ....60.1445B. doi:10.1016/S0006-3495(91)82181-6. PMC 1260204. PMID 1663794.
  4. ^ Brown, Jay C. (February 13, 2021). "Role of Gene Length in Control of Human Gene Expression: Chromosome-Specific and Tissue-Specific Effects". International Journal of Genomics. 2021: e8902428. doi:10.1155/2021/8902428. PMC 7911607. PMID 33688492.
  5. ^ "av - Editorial Board". Hindawi.
  6. ^ "Emeritus Faculty".
  7. ^ Brown, Jay C. (September 12, 2019). "Control of human testis-specific gene expression". PLOS ONE. 14 (9): e0215184. Bibcode:2019PLoSO..1415184B. doi:10.1371/journal.pone.0215184. PMC 6742485. PMID 31514204.
  8. ^ "Jay C. Brown". scholar.google.com.
  9. ^ Thach, R. E.; Sundararajan, T. A.; Dewey, K. F.; Brown, J. C.; Doty, Paul (January 1, 1966). "Translation of Synthetic Messenger RNA". Cold Spring Harbor Symposia on Quantitative Biology. 31: 85–97. doi:10.1101/SQB.1966.031.01.015. PMID 4295326 – via symposium.cshlp.org.
  10. ^ Thach, R. E.; Dewey, K. F.; Brown, J. C.; Doty, Paul (July 22, 1966). "Formylmethionine Codon AUG as an Initiator of Polypeptide Synthesis". Science. 153 (3734): 416–418. Bibcode:1966Sci...153..416T. doi:10.1126/science.153.3734.416. PMID 5328567. S2CID 45022863.
  11. ^ Brown, J. C.; Doty, P. (February 11, 1971). "Kinetic preference for initiation of protein synthesis at AUG codons". Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis. 228 (3): 746–748. doi:10.1016/0005-2787(71)90740-4. PMID 4929431 – via PubMed.
  12. ^ Brown, J. C. (December 1, 1971). "Surface glycoprotein characteristic of the differentiated state of neuroblastoma C-1300 cells". Experimental Cell Research. 69 (2): 440–442. doi:10.1016/0014-4827(71)90247-3. PMID 5163635 – via ScienceDirect.
  13. ^ Brown, J. C. (March 9, 1972). "Cell surface glycoproteins I: Accumulation of a glycoprotein on the outer surface of mouse LS cells during mitosis". Journal of Supramolecular Structure. 1 (1): 1–7. doi:10.1002/jss.400010102. PMID 4650442.
  14. ^ Hunt, Richard C.; Brown, Jay C. (January 1, 1974). "Surface glycoproteins of mouse L cells". Biochemistry. 13 (1): 22–28. doi:10.1021/bi00698a004. PMID 4855553.
  15. ^ Hunt, Richard C.; Gold, Elizabeth; Brown, Jay C. (December 16, 1975). "Cell cycle dependent exposure of a high molecular weight protein on the surface of mouse L cells". Biochimica et Biophysica Acta (BBA) - Biomembranes. 413 (3): 453–458. doi:10.1016/0005-2736(75)90128-5. PMID 1238124 – via ScienceDirect.
  16. ^ "Role of Polycomb Repressive Complex 2 in Regulation of Human Transcription Factor Gene Expression" (PDF).
  17. ^ Brown, Jay C. (January 27, 2023). "Backup transcription factor binding sites protect human genes from mutations in the promoter": 2023.01.27.525856. doi:10.1101/2023.01.27.525856. S2CID 256417694 – via bioRxiv. {{cite journal}}: Cite journal requires |journal= (help)
  18. ^ Newcomb, W W; Brown, J C (July 9, 1981). "Role of the vesicular stomatitis virus matrix protein in maintaining the viral nucleocapsid in the condensed form found in native virions". Journal of Virology. 39 (1): 295–299. doi:10.1128/jvi.39.1.295-299.1981. PMC 171289. PMID 6268817.
  19. ^ Newcomb, W W; Tobin, G J; McGowan, J J; Brown, J C (March 9, 1982). "In vitro reassembly of vesicular stomatitis virus skeletons". Journal of Virology. 41 (3): 1055–1062. doi:10.1128/jvi.41.3.1055-1062.1982. PMC 256843. PMID 6284961.
  20. ^ Thomas, D; Newcomb, W W; Brown, J C; Wall, J S; Hainfeld, J F; Trus, B L; Steven, A C (May 9, 1985). "Mass and molecular composition of vesicular stomatitis virus: a scanning transmission electron microscopy analysis". Journal of Virology. 54 (2): 598–607. doi:10.1128/jvi.54.2.598-607.1985. PMC 254833. PMID 2985822.
  21. ^ Baker, T. S.; Newcomb, W. W.; Olson, N. H.; Cowsert, L. M.; Olson, C.; Brown, J. C. (December 9, 1991). "Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction". Biophysical Journal. 60 (6): 1445–1456. Bibcode:1991BpJ....60.1445B. doi:10.1016/S0006-3495(91)82181-6. PMC 1260204. PMID 1663794.
  22. ^ Newcomb, W. W.; Brown, J. C. (February 9, 1991). "Structure of the herpes simplex virus capsid: effects of extraction with guanidine hydrochloride and partial reconstitution of extracted capsids". Journal of Virology. 65 (2): 613–620. doi:10.1128/JVI.65.2.613-620.1991. PMC 239799. PMID 1846187.
  23. ^ Baker, T. S.; Newcomb, W. W.; Booy, F. P.; Brown, J. C.; Steven, A. C. (February 1990). "Three-dimensional structures of maturable and abortive capsids of equine herpesvirus 1 from cryoelectron microscopy | Journal of Virology". Journal of Virology. 64 (2): 563–573. doi:10.1128/jvi.64.2.563-573.1990. PMC 249145. PMID 2153224.
  24. ^ Newcomb, W. W.; Homa, F. L.; Thomsen, D. R.; Ye, Z.; Brown, J. C. (September 9, 1994). "Cell-free assembly of the herpes simplex virus capsid". Journal of Virology. 68 (9): 6059–6063. doi:10.1128/JVI.68.9.6059-6063.1994. PMC 237013. PMID 8057482.
  25. ^ Ww, Newcomb; Fl, Homa; Dr, Thomsen; Bl, Trus; N, Cheng; A, Steven; F, Booy; Jc, Brown (May 9, 1999). "Assembly of the herpes simplex virus procapsid from purified components and identification of small complexes containing the major capsid and scaffolding proteins". Journal of Virology. 73 (5): 4239–4250. doi:10.1128/JVI.73.5.4239-4250.1999. PMC 104203. PMID 10196320.
  26. ^ Heymann, J. Bernard; Cheng, Naiqian; Newcomb, William W.; Trus, Benes L.; Brown, Jay C.; Steven, Alasdair C. (May 9, 2003). "Dynamics of herpes simplex virus capsid maturation visualized by time-lapse cryo-electron microscopy". Nature Structural Biology. 10 (5): 334–341. doi:10.1038/nsb922. PMID 12704429. S2CID 21039842 – via PubMed.
  27. ^ Trus, Benes L.; Booy, Frank P.; Newcomb, William W.; Brown, Jay C.; Homa, Fred L.; Thomsen, Darrell R.; Steven, Alasdair C. (November 1, 1996). "The herpes simplex virus procapsid: structure, conformational changes upon maturation, and roles of the triplex proteins VP19c and VP23 in assembly". Journal of Molecular Biology. 263 (3): 447–462. doi:10.1016/S0022-2836(96)80018-0. PMID 8918600 – via ScienceDirect.
  28. ^ Newcomb, W. W.; Juhas, R. M.; Thomsen, D. R.; Homa, F. L.; Burch, A. D.; Weller, S. K.; Brown, J. C. (November 9, 2001). "The UL6 gene product forms the portal for entry of DNA into the herpes simplex virus capsid". Journal of Virology. 75 (22): 10923–10932. doi:10.1128/JVI.75.22.10923-10932.2001. PMC 114672. PMID 11602732.
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