Richard H. Ebright

Last updated

Richard H. Ebright
Born
Richard High Ebright
Alma mater Harvard University
Awards Searle Scholar Award (1989)
Fellow of the American Association for the Advancement of Science (2004)
National Institutes of Health MERIT Award (2013) [1]
Scientific career
Fields Molecular biology
Institutions
Thesis Structure-function studies with the catabolite gene activator protein (CAP) of Escherichia coli  (1986)

Richard High Ebright is an American molecular biologist. He is the Board of Governors Professor of Chemistry and Chemical Biology at Rutgers University and Laboratory Director at the Waksman Institute of Microbiology. [1] [2]

Contents

Early life and education

Ebright received an A.B. summa cum laude in biology from Harvard University in 1981 and a PhD in microbiology and molecular genetics from Harvard University in 1987. [1] [2] He was a junior fellow of the Harvard Society of Fellows from 1984 to 1987. [2]

Career

Ebright was appointed as a faculty member in the Department of Chemistry at Rutgers University and as a Laboratory Director at the Waksman Institute of Microbiology in 1987. [2] He was co-appointed as an Investigator of the Howard Hughes Medical Institute from 1997 to 2013. [2]

Ebright's research has included the experimental demonstration that amino-acid-base contacts mediate DNA sequence recognition in protein-DNA interaction, [3] the determination of the three-dimensional structural organization of the transcription initiation complex; [4] [5] [6] the demonstration that transcription start-site selection and initial transcription involve "DNA scrunching", [7] [8] [9] the demonstration that transcription activation can proceed by a "recruitment" mechanism, [10] [11] [12] the demonstration that bacterial transcription-translation coupling involves direct physical bridging of RNA polymerase and a ribosome by NusA and NusG, [13] the demonstration that bacterial Rho-dependent transcription termination involves the molecular-motor activity of the termination factor Rho, [14] [15] and the identification of novel antibacterial drug targets in bacterial RNA polymerase. [16] [17]

In 1994, Ebright was awarded the American Society of Biochemistry and Molecular Biology Schering-Plough Award for his research on transcription activation. [18] In 1995, he received the Academic Press Walter J. Johnson Prize. [19] In 2013, he received a National Institutes of Health MERIT Award. [20] He was elected as a Fellow of the American Academy of Microbiology in 1996, [21] the American Association for the Advancement of Science in 2004, [22] the Infectious Diseases Society of America in 2011, [23] and the American Academy of Arts and Sciences in 2016. [24] He is the subject of a piece named "The Making of a Scientist" in a high school textbook published by NCERT (and recommended by the CBSE) in India. [25]

He has opposed the proliferation of laboratories working on biological weapons agents and has supported the strengthening of biosafety and biosecurity measures to reduce risks of release of biological weapons. [26]

COVID-19 origins

Ebright has stated that the genome and properties of SARS-CoV-2 provide no basis to conclude the virus was engineered as a bioweapon, [27] [28] but he also has stated that the possibility that the virus entered humans through a laboratory accident cannot be dismissed and has called for a thorough investigation of the origin of the pandemic and for measures to reduce the risk of future pandemics. [29] [30] [31]

Ebright has accused NIAID director Anthony Fauci, NIH director Francis Collins and deputy director Lawrence Tabak of "lying to the public", about their past and continuing denials of NIH funding having been utilized for gain-of-function experiments at the Wuhan Institute of Virology. [32] [33]

Ebright and fellow Rutgers University professor Bryce Nickels, who founded the non-profit advocacy group Biosafety Now with Ebright, have been vocal proponents of the COVID-19 lab leak theory. [34] The Los Angeles Times's Michael Hiltzik has said that Ebright has "been posting online insulations or accusations" of fraud, perjury, and murder regarding scientists that have supported a zoonotic origin of COVID-19 and dismissed the lab leak theory. Ebright has compared Fauci to Cambodian leader Pol Pot and claimed that Fauci's actions "likely killed 20 million people" and wrote that Peter Daszak was the author of a grant that "many people consider" to be the "‘Blueprint’ for SARS-CoV2". In 2024, Ebright was the subject of a formal complaint to Rutgers by 12 researchers, some of who said that Ebright was engaging in defamation and intimidation against them for their research that found a zoonotic origin of COVID-19 to be the most likely origin and found the lab leak to be "implausible". [35] In response, Ebright said that the complaint misrepresented him, and that he had never "threatened or incited violence against any of the signatories" [35] and in response to the letter he referred to the signatories of the letter as "provably coauthors of fraudsters and perjurers", claiming that the letter was "a crude effort to silence their opponents and, thereby, to prop up their collapsing narrative." [34]

Related Research Articles

<span class="mw-page-title-main">Transcription (biology)</span> Process of copying a segment of DNA into RNA

Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins produce messenger RNA (mRNA). Other segments of DNA are transcribed into RNA molecules called non-coding RNAs (ncRNAs).

<span class="mw-page-title-main">Non-coding RNA</span> Class of ribonucleic acid that is not translated into proteins

A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR.

<span class="mw-page-title-main">RNA polymerase</span> Enzyme that synthesizes RNA from DNA

In molecular biology, RNA polymerase, or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template.

<span class="mw-page-title-main">Transcription preinitiation complex</span> Complex of proteins necessary for gene transcription in eukaryotes and archaea

The preinitiation complex is a complex of approximately 100 proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. The preinitiation complex positions RNA polymerase II at gene transcription start sites, denatures the DNA, and positions the DNA in the RNA polymerase II active site for transcription.

<span class="mw-page-title-main">RNA polymerase II</span> Protein complex that transcribes DNA

RNA polymerase II is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryotic cells. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. A wide range of transcription factors are required for it to bind to upstream gene promoters and begin transcription.

<span class="mw-page-title-main">General transcription factor</span> Class of protein transcription factors

General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites (promoter) on DNA to activate transcription of genetic information from DNA to messenger RNA. GTFs, RNA polymerase, and the mediator constitute the basic transcriptional apparatus that first bind to the promoter, then start transcription. GTFs are also intimately involved in the process of gene regulation, and most are required for life.

<span class="mw-page-title-main">Catabolite activator protein</span> Trans-acting transcriptional activator

Catabolite activator protein is a trans-acting transcriptional activator that exists as a homodimer in solution. Each subunit of CAP is composed of a ligand-binding domain at the N-terminus and a DNA-binding domain at the C-terminus. Two cAMP molecules bind dimeric CAP with negative cooperativity. Cyclic AMP functions as an allosteric effector by increasing CAP's affinity for DNA. CAP binds a DNA region upstream from the DNA binding site of RNA Polymerase. CAP activates transcription through protein-protein interactions with the α-subunit of RNA Polymerase. This protein-protein interaction is responsible for (i) catalyzing the formation of the RNAP-promoter closed complex; and (ii) isomerization of the RNAP-promoter complex to the open conformation. CAP's interaction with RNA polymerase causes bending of the DNA near the transcription start site, thus effectively catalyzing the transcription initiation process. CAP's name is derived from its ability to affect transcription of genes involved in many catabolic pathways. For example, when the amount of glucose transported into the cell is low, a cascade of events results in the increase of cytosolic cAMP levels. This increase in cAMP levels is sensed by CAP, which goes on to activate the transcription of many other catabolic genes.

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

The TATA-binding protein (TBP) is a general transcription factor that binds to a DNA sequence called the TATA box. This DNA sequence is found about 30 base pairs upstream of the transcription start site in some eukaryotic gene promoters.

<span class="mw-page-title-main">T7 RNA polymerase</span> Class of enzymes

T7 RNA Polymerase is an RNA polymerase from the T7 bacteriophage that catalyzes the formation of RNA from DNA in the 5'→ 3' direction.

cAMP receptor protein Regulatory protein in bacteria

cAMP receptor protein is a regulatory protein in bacteria.

<span class="mw-page-title-main">Eukaryotic transcription</span> Transcription is heterocatalytic function of DNA

Eukaryotic transcription is the elaborate process that eukaryotic cells use to copy genetic information stored in DNA into units of transportable complementary RNA replica. Gene transcription occurs in both eukaryotic and prokaryotic cells. Unlike prokaryotic RNA polymerase that initiates the transcription of all different types of RNA, RNA polymerase in eukaryotes comes in three variations, each translating a different type of gene. A eukaryotic cell has a nucleus that separates the processes of transcription and translation. Eukaryotic transcription occurs within the nucleus where DNA is packaged into nucleosomes and higher order chromatin structures. The complexity of the eukaryotic genome necessitates a great variety and complexity of gene expression control.

<span class="mw-page-title-main">Transcription factor II B</span> Mammalian protein found in Homo sapiens

Transcription factor II B (TFIIB) is a general transcription factor that is involved in the formation of the RNA polymerase II preinitiation complex (PIC) and aids in stimulating transcription initiation. TFIIB is localised to the nucleus and provides a platform for PIC formation by binding and stabilising the DNA-TBP complex and by recruiting RNA polymerase II and other transcription factors. It is encoded by the TFIIB gene, and is homologous to archaeal transcription factor B and analogous to bacterial sigma factors.

<span class="mw-page-title-main">GTF2H1</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIH subunit 1 is a protein that in humans is encoded by the GTF2H1 gene.

<span class="mw-page-title-main">GTF2F2</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIF subunit 2 is a protein that in humans is encoded by the GTF2F2 gene.

<span class="mw-page-title-main">B recognition element</span>

The B recognition element (BRE) is a DNA sequence found in the promoter region of most genes in eukaryotes and Archaea. The BRE is a cis-regulatory element that is found immediately near TATA box, and consists of 7 nucleotides. There are two sets of BREs: one (BREu) found immediately upstream of the TATA box, with the consensus SSRCGCC; the other (BREd) found around 7 nucleotides downstream, with the consensus RTDKKKK.

<span class="mw-page-title-main">GTF2E2</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIE subunit 2 (GTF2E2), also known as transcription initiation factor IIE subunit beta (TFIIE-beta), is a protein that in humans is encoded by the GTF2E2 gene.

<span class="mw-page-title-main">GTF2E1</span> Human protein-coding gene

General transcription factor IIE subunit 1 (GTF2E1), also known as transcription initiation factor IIE subunit alpha (TFIIE-alpha), is a protein that in humans is encoded by the GTF2E1 gene.

<span class="mw-page-title-main">Cas9</span> Microbial protein found in Streptococcus pyogenes M1 GAS

Cas9 is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications. Its main function is to cut DNA and thereby alter a cell's genome. The CRISPR-Cas9 genome editing technique was a significant contributor to the Nobel Prize in Chemistry in 2020 being awarded to Emmanuelle Charpentier and Jennifer Doudna.

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

Abortive initiation, also known as abortive transcription, is an early process of genetic transcription in which RNA polymerase binds to a DNA promoter and enters into cycles of synthesis of short mRNA transcripts which are released before the transcription complex leaves the promoter. This process occurs in both eukaryotes and prokaryotes. Abortive initiation is typically studied in the T3 and T7 RNA polymerases in bacteriophages and in E. coli.

Transcription-translation coupling is a mechanism of gene expression regulation in which synthesis of an mRNA (transcription) is affected by its concurrent decoding (translation). In prokaryotes, mRNAs are translated while they are transcribed. This allows communication between RNA polymerase, the multisubunit enzyme that catalyzes transcription, and the ribosome, which catalyzes translation. Coupling involves both direct physical interactions between RNA polymerase and the ribosome, as well as ribosome-induced changes to the structure and accessibility of the intervening mRNA that affect transcription.

References

  1. 1 2 3 "Ebright, Richard H." Department of Chemistry, Rutgers University. Retrieved August 21, 2020.
  2. 1 2 3 4 5 "Dr. Richard H. Ebright". Waksman Institute, Rutgers University. Retrieved October 6, 2011.
  3. ↑ Ebright, R. H.; Cossart, P.; Gicquel-Sanzey, B.; Beckwith, J. (1984). "Mutations that alter the DNA sequence specificity of the catabolite gene activator protein of E. coli". Nature. 311 (5983): 232–235. Bibcode:1984Natur.311..232E. doi:10.1038/311232a0. PMID   6090927. S2CID   4261408.
  4. ↑ Mekler, V.; Kortkhonjia, E.; Mukhopadhyay, J.; Knight, J.; Revyakin, A.; Kapanidis, A.; Niu, W.; Ebright, Y.; Levy, R.; Ebright, R. H. (2002). "Structural organization of bacterial RNA polymerase holoenzyme and the RNA polymerase-promoter open complex". Cell. 108 (5): 599–614. doi: 10.1016/S0092-8674(02)00667-0 . PMID   11893332. S2CID   4938696.
  5. ↑ Zhang, Y.; Feng, Y.; Chatterjee, S.; Tuske, S.; Ho, M. X.; Arnold, E.; Ebright, R. H. (2012). "Structural Basis of Transcription Initiation". Science. 338 (6110): 1076–80. Bibcode:2012Sci...338.1076Z. doi:10.1126/science.1227786. PMC   3593053 . PMID   23086998.
  6. ↑ Chakraborty, A.; Wang, D.; Ebright, Y.; Korlann, Y.; Kortkhonjia, E.; Kim, T.; Chowdhury, S.; Wigneshweraraj, S.; Irschik, H.; Jansen, R.; Nixon, B.T.; Knight, J.; Weiss, S.; Ebright, R. H. (2012). "Opening and closing of the bacterial RNA polymerase clamp". Science. 337 (6094): 591–595. Bibcode:2012Sci...337..591C. doi:10.1126/science.1218716. PMC   3626110 . PMID   22859489.
  7. ↑ Kapanidis, A. N.; Margeat, E.; Ho, S. O.; Kortkhonjia, E.; Weiss, S.; Ebright, R. H. (2006). "Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism". Science. 314 (5802): 1144–1147. Bibcode:2006Sci...314.1144K. doi:10.1126/science.1131399. PMC   2754788 . PMID   17110578.
  8. ↑ Revyakin, A.; Liu, C.; Ebright, R. H.; Strick, T. (2006). "Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching". Science. 314 (5802): 1139–1143. Bibcode:2006Sci...314.1139R. doi:10.1126/science.1131398. PMC   2754787 . PMID   17110577.
  9. ↑ Winkelman, J.; Vvedenskaya, I.; Zhang, Y.; Bird, J.; Taylor, D.; Gourse, R.; Ebright, R.; Nickels, B. (2016). "Multiplexed protein-DNA cross-linking: Scrunching in transcription start site selection". Science. 351 (6277): 1090–1093. Bibcode:2016Sci...351.1090W. doi:10.1126/science.aad6881. PMC   4797950 . PMID   26941320.
  10. ↑ Heyduk, T.; Lee, J.; Ebright, Y.; Blatter, E.; Zhou, Y.; Ebright, R. H. (1993). "CAP interacts with RNA polymerase in solution in the absence of promoter DNA". Nature. 364 (6437): 548–549. Bibcode:1993Natur.364..548H. doi:10.1038/364548a0. PMID   8393148. S2CID   4248533.
  11. ↑ Benoff, B.; Yang, H.; Lawson, C. L.; Parkinson, G.; Liu, J.; Blatter, E.; Ebright, Y. W.; Berman, H. M.; Arnold, E.; Ebright, R. H. (2002). "Structural basis of transcription activation: the CAP-alphaCTD-DNA complex". Science. 297 (5586): 1562–1566. Bibcode:2002Sci...297.1562B. doi:10.1126/science.1076376. PMID   12202833. S2CID   17422837.
  12. ↑ Feng, Y.; Zhang, Y.; Ebright, R. H. (2016). "Structural basis of transcription activation". Science. 352 (6291): 1330–1333. Bibcode:2016Sci...352.1330F. doi:10.1126/science.aaf4417. PMC   4905602 . PMID   27284196.
  13. ↑ Wang, C.; Molodtsov, V.; Firlar, E.; Kaelber, J.; Blaha, G.; Su, M. & Ebright, R. H. (2020). "Structural basis of transcription-translation coupling". Science. 369 (6509): 1359–1365. Bibcode:2020Sci...369.1359W. doi:10.1126/science.abb5317. PMC   7566311 . PMID   32820061.
  14. ↑ Molodtsov, V.; Wang, C.; Firlar, E.; Kaelber, J. & Ebright, R. H. (2023). "Structural basis of Rho-dependent transcription termination". Nature. 614 (7947): 367–374. Bibcode:2023Natur.614..367M. doi:10.1038/s41586-022-05658-1. PMC   9911385 . PMID   36697824.
  15. ↑ Rashid, F. & Berger, J. (2023). "Protein structure terminates doubt about how transcription stops". Nature. 614 (7947): 237–238. Bibcode:2023Natur.614..237R. doi:10.1038/d41586-023-00121-1. PMID   36697726.
  16. ↑ Mukhopadhyay, J.; Das, K.; Ismail, S.; Koppstein, D.; Jang, M.; Hudson, B.; Sarafianos, S.; Tuske, S.; Patel, J.; Jansen, R.; Irschik, H.; Arnold, E. & Ebright, R. H. (2008). "The RNA polymerase "switch region" is a target for inhibitors". Cell. 135 (2): 295–307. doi:10.1016/j.cell.2008.09.033. PMC   2580802 . PMID   18957204.
  17. ↑ Maffioli, S.; Zhang, Y.; Degen, D.; Carzaniga, T.; Del Gatto, G.; Serina, S.; Monciardini, P.; Mazzetti, C.; Guglierame, P.; Candiani, G.; Chiriac, A. I.; Facchetti, G.; Kaltofen, P.; Sahl, H.-G.; Dehò, G.; Donadio, S. & Ebright, R. H. (2017). "Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase". Cell. 169 (7): 1240–1248. doi:10.1016/j.cell.2017.05.042. PMC   5542026 . PMID   28622509.
  18. ↑ "ASBMB/Schering-Plough Research Institute Award" . Retrieved October 8, 2011.
  19. ↑ "The Walter J. Johnson Prize, 1995". Journal of Molecular Biology. 251 (3): 329. 1995. PMID   7650734.
  20. ↑ "Gifts & Grants". Rutgers University Faculty and Staff Bulletin. June 12, 2013. Retrieved June 12, 2013.
  21. ↑ "American Academy of Microbiology Fellowship Directory". Archived from the original on August 7, 2011. Retrieved October 8, 2011.
  22. ↑ "AAAS Council Honors 308 Members for Their Contributions to Science" (Press release). AAAS. November 1, 2004. Retrieved October 8, 2011.
  23. ↑ "Congratulations, New IDSA Fellows!". IDSA News. July–August 2011. Retrieved October 8, 2011.
  24. ↑ "American Academy of Arts and Sciences Elects 213 National and International Scholars, Artists, Philanthropists, and Business and Civic Leaders" (Press release). American Academy of Arts and Sciences. April 20, 2016. Retrieved April 20, 2016.
  25. ↑ Footprints Without Feet (December 2017 ed.). India: NCERT. 2007. pp. 32–38. ISBN   978-81-7450-709-9.
  26. ↑ See, for example, the following:
    Sources describing his opposition to proliferation of laboratories working on biological weapons agents:Sources describing his support for strengthening of biosafety and biosecurity measures:
  27. ↑ Taylor, A. (January 29, 2020). "Experts debunk fringe theory linking China's coronavirus to weapons research". The Washington Post.
  28. ↑ Firozi, P. (February 17, 2020). "Tom Cotton keeps repeating a coronavirus fringe theory that scientists have disputed". The Washington Post.
  29. ↑ Cohen, J. (January 31, 2020). "Mining coronavirus genomes for clues to the outbreak's origins". Science.
  30. ↑ Warrick, J.; Nakashima, E.; Harris, S.; Fifield, A. (May 1, 2020). "Chinese lab conducted extensive research on deadly bat viruses, but there is no evidence of accidental release". The Washington Post.
  31. ↑ Zimmer, C.; Gorman, J. (June 7, 2021). "Fight Over Covid's Origins Renews Debate on Risks of Lab Work". The New York Times.
  32. ↑ Schemmel, Alec (October 21, 2021). "NIH letter appears to conflict with Fauci, Collins claims about Wuhan lab" . Retrieved November 9, 2021.
  33. ↑ "The repeated claim that Fauci lied to Congress about 'gain-of-function' research". Washington Post. Retrieved November 9, 2021.
  34. 1 2 Kaiser, Jocelyn (March 15, 2024). 'Lab-leak' proponents at Rutgers accused of defaming and intimidating COVID-19 origin researchers (Report). Science. doi:10.1126/science.znoov39.
  35. 1 2 Hiltzik, Michael (March 20, 2024). "Column: Two Rutgers professors are accused of poisoning the debate over COVID's origins. Here's why". The Los Angeles Times . Retrieved March 20, 2024.
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