Victor Ambros

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Victor Ambros
Victor Ambros, 2024 Nobel Prize Laureate in Medicine.jpg
Ambros in 2024
Born (1953-12-01) December 1, 1953 (age 71) [1]
Hanover, New Hampshire, U.S.
Alma mater Massachusetts Institute of Technology (BS, PhD)
Known forDiscovery of microRNA
Awards
Scientific career
Fields Biology
Institutions M.I.T. Center for Cancer Research (1975–1976)
Massachusetts Institute of Technology (1976–1979)
Harvard University (1985–1992)
Dartmouth College (1992–2001)
Dartmouth Medical School (2001–2007)
University of Massachusetts Medical School (2008–)
Thesis The protein covalently linked to the 5'-end of poliovirus RNA  (1979)
Doctoral advisor David Baltimore
Website umassmed.edu/ambroslab/

Victor R. Ambros (born December 1, 1953) is an American developmental biologist and Nobel Laureate who discovered the first known microRNA (miRNA). He is a professor at the University of Massachusetts Medical School. He completed both his undergraduate and doctoral studies at the Massachusetts Institute of Technology. Ambros received the Nobel Prize in Physiology or Medicine in 2024 for his research on microRNA. [2]

Contents

Biography

Early life and education

Ambros was born in New Hampshire. His father, Longin, was a Polish war refugee. [3] Victor grew up on a small dairy farm in Hartland, Vermont, in a family of eight children and attended Woodstock Union High School. [4]

From the Massachusetts Institute of Technology, Ambros received a Bachelor of Science with a major in biology in 1975 and a Doctor of Philosophy in biology in 1979. [5] [6] [7] His doctoral supervisor was David Baltimore, a 1975 Nobel laureate in Physiology or Medicine. [8] Ambros continued his research at MIT as the first postdoctoral fellow in the lab of future Nobel laureate H. Robert Horvitz. [9]

Career

Ambros became a faculty member at Harvard University in 1984. However, Harvard denied tenure to Ambros shortly after he discovered what is now known as microRNA. [10] About this, Baltimore later said in 2008: "They lost a potential Nobel laureate because they simply didn’t see in him the potential that he had ... It’s the nature of a seminal discovery that it’s seminal in retrospect. You can’t know ahead of time." [10]

Ambros joined the faculty of Dartmouth College in 1992. [9] He joined the faculty at the University of Massachusetts Medical School in 2008, and currently holds the title of Silverman Professor of Natural Sciences in the program in Molecular Medicine, endowed by his former Dartmouth student, Howard Scott Silverman. [2] [9] [11]

Research

In 1993, Ambros and his co-workers Rosalind Lee and Rhonda Feinbaum [12] reported in the journal Cell [13] that they had discovered single-stranded non-protein-coding regulatory RNA molecules in the organism C. elegans. Previous research, including work by Ambros and Horvitz, [14] [15] had revealed that a gene known as lin-4 was important for normal larval development of C. elegans, a nematode often studied as a model organism. Specifically, lin-4 was responsible for the progressive repression of the protein LIN-14 during larval development of the worm; mutant worms deficient in lin-4 function had persistently high levels of LIN-14 and displayed developmental timing defects. [15]

Ambros and colleagues found that lin-4, unexpectedly, did not encode a regulatory protein. Instead, it gave rise to some small RNA molecules, 22 and 61 nucleotides in length, which Ambros called lin-4S (short) and lin-4L (long). Sequence analysis showed that lin-4S was part of lin-4L: lin-4L was predicted to form a stem-loop structure, with lin-4S contained in one of the arms, the 5' arm. Furthermore, Ambros, together with Gary Ruvkun (Harvard), discovered that lin-4S was partially complementary to several sequences in the 3' untranslated region of the messenger RNA encoding the LIN-14 protein. [16] Ambros and colleagues hypothesized and later determined that lin-4 could regulate LIN-14 through binding of lin-4S to these sequences in the lin-14 transcript in a type of antisense RNA mechanism. [17]

In 2000, another C. elegans small RNA regulatory molecule, let-7, was characterized by the Ruvkun lab [18] and found to be conserved in many species, including vertebrates. [19] These discoveries, among others, confirmed that Ambros had in fact discovered a class of small RNAs with conserved functions, now known as microRNA. [20]

Ambros was elected to the United States National Academy of Sciences in 2007. [21] He was elected a Fellow of the American Academy of Arts and Sciences in 2011. [22] In 2024 he shared the Nobel Prize in Physiology and Medicine with Gary Ruvkun "for the discovery of microRNA and its role in post-transcriptional gene regulation". [2]

Awards

Ambros received Gruber Prize in Genetics alongside Gary Ruvkun in 2014. Genetics laureates.jpg
Ambros received Gruber Prize in Genetics alongside Gary Ruvkun in 2014.

Related Research Articles

<i>Caenorhabditis elegans</i> Free-living species of nematode

Caenorhabditis elegans is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek caeno- (recent), rhabditis (rod-like) and Latin elegans (elegant). In 1900, Maupas initially named it Rhabditides elegans. Osche placed it in the subgenus Caenorhabditis in 1952, and in 1955, Dougherty raised Caenorhabditis to the status of genus.

microRNA Small non-coding ribonucleic acid molecule

Micro ribonucleic acid are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in messenger RNA (mRNA) molecules, then silence said mRNA molecules by one or more of the following processes:

Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM is an American biologist whose research on the nematode worm Caenorhabditis elegans was awarded the 2002 Nobel Prize in Physiology or Medicine, together with Sydney Brenner and John E. Sulston, whose "seminal discoveries concerning the genetic regulation of organ development and programmed cell death" were "important for medical research and have shed new light on the pathogenesis of many diseases".

<span class="mw-page-title-main">Phillip Allen Sharp</span> American geneticist and molecular biologist

Phillip Allen Sharp is an American geneticist and molecular biologist who co-discovered RNA splicing. He shared the 1993 Nobel Prize in Physiology or Medicine with Richard J. Roberts for "the discovery that genes in eukaryotes are not contiguous strings but contain introns, and that the splicing of messenger RNA to delete those introns can occur in different ways, yielding different proteins from the same DNA sequence". He has been selected to receive the 2015 Othmer Gold Medal.

<span class="mw-page-title-main">Michael Stuart Brown</span> American geneticist and Nobel laureate (born 1941)

Michael Stuart Brown ForMemRS NAS AAA&S APS is an American geneticist and Nobel laureate. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of cholesterol metabolism.

<span class="mw-page-title-main">Craig Mello</span> American biologist (b.1960)

Craig Cameron Mello is an American biologist and professor of molecular medicine at the University of Massachusetts Medical School in Worcester, Massachusetts. He was awarded the 2006 Nobel Prize for Physiology or Medicine, along with Andrew Z. Fire, for the discovery of RNA interference. This research was conducted at the Carnegie Institution of Washington and published in 1998. Mello has been a Howard Hughes Medical Institute investigator since 2000.

<span class="mw-page-title-main">Andrew Fire</span> American biologist and professor of pathology and genetics

Andrew Zachary Fire is an American biologist and professor of pathology and of genetics at the Stanford University School of Medicine. He was awarded the 2006 Nobel Prize in Physiology or Medicine, along with Craig C. Mello, for the discovery of RNA interference (RNAi). This research was conducted at the Carnegie Institution of Washington and published in 1998.

The Let-7 microRNA precursor gives rise to let-7, a microRNA (miRNA) involved in control of stem-cell division and differentiation. let-7, short for "lethal-7", was discovered along with the miRNA lin-4 in a study of developmental timing in C. elegans, making these miRNAs the first ever discovered. let-7 was later identified in humans as the first human miRNA, and is highly conserved across many species. Dysregulation of let-7 contributes to cancer development in humans by preventing differentiation of cells, leaving them stuck in a stem-cell like state. let-7 is therefore classified as a tumor suppressor.

lin-4 microRNA precursor

In molecular biology lin-4 is a microRNA (miRNA) that was identified from a study of developmental timing in the nematode Caenorhabditis elegans. It was the first to be discovered of the miRNAs, a class of non-coding RNAs involved in gene regulation. miRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a 21 nucleotide product. The extents of the hairpin precursors are not generally known and are estimated based on hairpin prediction. The products are thought to have regulatory roles through complete or partial complementarity to mRNA. The lin-4 gene has been found to lie within a 4.11kb intron of a separate host gene.

<span class="mw-page-title-main">David Baulcombe</span> British plant scientist and geneticist

Sir David Charles Baulcombe is a British plant scientist and geneticist. As of October 2024 he was Head of Group, Gene Expression, in the Department of Plant Sciences at the University of Cambridge, and the Edward Penley Abraham Royal Society Research Professor and Regius Professor of Botany Emeritus at Cambridge. He held the Regius botany chair in that department from 2007 to 2020.

<span class="mw-page-title-main">LIN28</span>

Lin-28 homolog A is a protein that in humans is encoded by the LIN28 gene.

<span class="mw-page-title-main">Gary Ruvkun</span> American geneticist (born 1952)

Gary Bruce Ruvkun is an American molecular biologist and Nobel laureate at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston.

mir-48 microRNA is a microRNA which is found in nematodes, in which it controls developmental timing. It acts in the heterochronic pathway, where it controls the timing of cell fate decisions in the vulva and hypodermis during larval development.

MicroRNA sequencing (miRNA-seq), a type of RNA-Seq, is the use of next-generation sequencing or massively parallel high-throughput DNA sequencing to sequence microRNAs, also called miRNAs. miRNA-seq differs from other forms of RNA-seq in that input material is often enriched for small RNAs. miRNA-seq allows researchers to examine tissue-specific expression patterns, disease associations, and isoforms of miRNAs, and to discover previously uncharacterized miRNAs. Evidence that dysregulated miRNAs play a role in diseases such as cancer has positioned miRNA-seq to potentially become an important tool in the future for diagnostics and prognostics as costs continue to decrease. Like other miRNA profiling technologies, miRNA-Seq has both advantages and disadvantages.

In molecular biology mir-84 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

The Massry Prize was established in 1996, and is administered by the Meira and Shaul G. Massry Foundation. The Prize, of $40,000 and the Massry Lectureship, is bestowed upon scientists who have made substantial recent contributions in the biomedical sciences. Shaul G. Massry, M.D., who established the Massry Foundation, is Professor Emeritus of Medicine and Physiology and Biophysics at the Keck School of Medicine, University of Southern California. He served as Chief of its Division of Nephrology from 1974 to 2000. In 2009 the KECK School of Medicine was asked to administer the Prize, and has done so since that time. Out of 25 prizes bestowed until 2021, fourteen were awarded to future Nobel Prize winners. No Massry Prize was awarded in 2020, 2022 and 2023.

NamiRNAs are a type of miRNAs present in the nucleus, which can activate gene expression by binding to the enhancer, and therefore were named nuclear activating miRNAs (NamiRNAs), such as miR-24-1 and miR-26. These miRNAs loci are enriched with epigenetic markers that display enhancer activity like histone H3K27ac, P300/CBP, and DNaseI high-sensitivity loci. These NamiRNAs are able to activate the related enhancers and co-work with them to up-regulate the expression of neighboring genes. NamiRNAs are able to promote global gene transcription by binding their targeted enhancers in whole genome level.

Iva Susan Greenwald is an American biologist who is Professor of Cell and Molecular Biology at Columbia University. She studies cell-cell interactions and cell fate specification in C. elegans. She is particularly interested in LIN-12/Notch proteins, which is the receptor of one of the major signalling systems that determines the fate of cells.

Rosalind 'Candy' Lee is a biomedical scientist, best known for her breakthrough paper on the discovery of microRNA which was published in 1993. In 2002, Lee was joint recipient of the Newcomb Cleveland Prize, for the best paper published in the journal Science that year. In 2024, Lee's 1993 paper was cited as the seminal discovery for which the Nobel Prize in physiology or medicine was awarded that year, to co-author Victor Ambros, her husband.

LIN-14 is a nuclear protein that plays a crucial role in regulating developmental timing in the nematode worm Caenorhabditis elegans. It functions as a heterochronic gene, controlling the timing of developmental events during larval development. LIN-14 protein levels are high at the beginning of the first larval stage (L1) and then rapidly decline, which is essential for the transition from early to late cell fates. LIN-14 is a BEN domain transcription factor, capable of binding DNA and directly regulating gene expression. The protein's activity is tightly regulated by lin-4, a microRNA which inhibits LIN-14 protein synthesis through complementary base pairing with sequences in the lin-14 mRNA 3' untranslated region.

References

  1. ↑ "Who are Victor Ambros and Gary Ruvkun, winners of 2024 Nobel Prize in Medicine?". Hindustan Times. Archived from the original on October 7, 2024. Retrieved October 7, 2024.
  2. 1 2 3 4 "Press release: The Nobel Prize in Physiology or Medicine 2024". NobelPrize.org. Archived from the original on October 8, 2024. Retrieved October 7, 2024.
  3. ↑ "Obituary for Longin B. Ambros at Windsor". www.knightfuneralhomes.com. Archived from the original on October 7, 2024. Retrieved October 7, 2024.
  4. ↑ Gitschier, Jane (March 5, 2010). "In the Tradition of Science: An Interview with Victor Ambros". PLOS Genetics. 6 (3): e1000853. doi: 10.1371/journal.pgen.1000853 . ISSN   1553-7404. PMC   2832673 . PMID   20221254.
  5. ↑ "Victor R. Ambros, Ph.D." (PDF). UMass Chan Medical School. Archived (PDF) from the original on December 2, 2020. Retrieved October 9, 2024.
  6. ↑ "Victor Ambros '75, PhD '79 and Gary Ruvkun share Nobel Prize in Physiology or Medicine". MIT News | Massachusetts Institute of Technology. October 7, 2024. Archived from the original on October 8, 2024. Retrieved October 9, 2024.
  7. ↑ Ambros, Victor Robert. The protein covalently linked to the 5' end of poliovirus RNA (PhD thesis). Massachusetts Institute of Technology. hdl:1721.1/45675. ProQuest   303013951.
  8. ↑ "Victor R Ambros PhD". UMass Chan Medical School. Archived from the original on October 8, 2024. Retrieved October 9, 2024.
  9. 1 2 3 Office of Communications (October 7, 2024). "Former Dartmouth Professor Wins Nobel Prize". Dartmouth. Retrieved October 9, 2024.
  10. 1 2 Cooney, Elizabeth (September 14, 2008). "UMass scientist Ambros wins Lasker Award". Telegram & Gazette . Archived from the original on October 7, 2024. Retrieved October 7, 2024.
  11. ↑ Schwan, Henry. "'Long overdue': UMass Chan celebrates as researcher Victor Ambros wins Nobel Prize". The Worcester Telegram & Gazette. Retrieved October 9, 2024.
  12. ↑ Sedwick, Caitlin (May 13, 2013). "Victor Ambros: The broad scope of microRNAs". Journal of Cell Biology. 201 (4): 492–493. doi:10.1083/jcb.2014pi. PMC   3653358 . PMID   23671307.
  13. ↑ Lee, R. C.; Feinbaum, R. L.; Ambros, V. (1993). "The C. Elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14". Cell. 75 (5): 843–854. doi: 10.1016/0092-8674(93)90529-Y . PMID   8252621.
  14. ↑ Chalfie, M.; Horvitz, H. R.; Sulston, J. E. (1981). "Mutations that lead to reiterations in the cell lineages of C. Elegans". Cell. 24 (1): 59–69. doi:10.1016/0092-8674(81)90501-8. PMID   7237544. S2CID   33933388.
  15. 1 2 Ambros, V. (1989). "A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. Elegans". Cell. 57 (1): 49–57. doi:10.1016/0092-8674(89)90171-2. PMID   2702689. S2CID   13103224.
  16. ↑ Wightman, B.; Ha, I.; Ruvkun, G. (1993). "Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. Elegans". Cell. 75 (5): 855–862. doi: 10.1016/0092-8674(93)90530-4 . PMID   8252622.
  17. ↑ Lee, Rosalind C.; Feinbaum, Rhonda L.; Ambros, Victor (December 1993). "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14". Cell. 75 (5): 843–854. doi:10.1016/0092-8674(93)90529-Y. PMID   8252621.
  18. ↑ Reinhart, B. J.; Slack, F. J.; Basson, M.; Pasquinelli, A. E.; Bettinger, J. C.; Rougvie, A. E.; Horvitz, H. R.; Ruvkun, G. (2000). "The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans". Nature. 403 (6772): 901–906. Bibcode:2000Natur.403..901R. doi:10.1038/35002607. PMID   10706289. S2CID   4384503.
  19. ↑ Pasquinelli, A. E.; Reinhart, B. J.; Slack, F.; Martindale, M. Q.; Kuroda, M. I.; Maller, B.; Hayward, D. C.; Ball, E. E.; Degnan, B.; Müller, B.; Spring, P.; Srinivasan, J. R.; Fishman, A.; Finnerty, M.; Corbo, J.; Levine, J.; Leahy, M.; Davidson, P.; Ruvkun, E. (2000). "Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA". Nature. 408 (6808): 86–89. Bibcode:2000Natur.408...86P. doi:10.1038/35040556. PMID   11081512. S2CID   4401732.
  20. ↑ Bartel, David P. (March 2018). "Metazoan MicroRNAs". Cell. 173 (1): 20–51. doi:10.1016/j.cell.2018.03.006. PMC   6091663 . PMID   29570994.
  21. 1 2 "Victor R. Ambros – NAS". National Academy of Sciences. Retrieved October 9, 2024.
  22. 1 2 3 4 5 6 7 8 9 10 "Learn more about Victor Ambros". UMass Chan Medical School. October 7, 2024. Archived from the original on October 8, 2024. Retrieved October 9, 2024.
  23. ↑ "Newcomb Cleveland Prize Recipients". AAAS – The World's Largest General Scientific Society. July 5, 2013. Archived from the original on October 23, 2012. Retrieved March 23, 2018.
  24. ↑ "Rosenstiel Award Winners". Brandeis University. Archived from the original on August 4, 2017. Retrieved October 7, 2024.
  25. ↑ "Victor Ambros - Gairdner Foundation Award Winner". Gairdner Awards for Biomedical Research. October 7, 2024. Retrieved October 9, 2024.
  26. ↑ MGH Executive Committee on Research. "Warren Triennial Prize" . Retrieved October 9, 2024.
  27. ↑ "Victor R. Ambros, PhD | Dickson Prize in Medicine | University of Pittsburgh". The Dickson Prize in Medicine. Archived from the original on August 1, 2024. Retrieved October 9, 2024.
  28. ↑ Fessenden, Jim (November 10, 2014). "Victor Ambros awarded 2015 $3M Breakthrough Prize for co-discovery of microRNAs". UMass med NOW. University of Massachusetts Medical School. Archived from the original on September 6, 2015. Retrieved September 6, 2015.
  29. ↑ "Victor Ambros awarded 2016 March of Dimes prize for co-discovery of MicroRNAs". University of Massachusetts Medical School. May 3, 2016. Archived from the original on July 22, 2024. Retrieved September 9, 2016.
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