Victor Ambros

Last updated
Victor R. Ambros
Ambros3.jpg
Born (1953-12-01) December 1, 1953 (age 69)
Hanover, New Hampshire
Alma mater Massachusetts Institute of Technology (B.S., 1975) (Ph.D., 1979)
Known fordiscovery of the first known microRNA
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–)

Victor R. Ambros (born 1953, Hanover, New Hampshire) is an American developmental biologist who discovered the first known microRNA (miRNA). He is a professor at the University of Massachusetts Medical School in Worcester, Massachusetts.

Contents

Background

Ambros was born in New Hampshire. His father was a Polish war refugee and Victor grew up on a small dairy farm in Hartland, Vermont in a family of eight children, and went to school at Woodstock Union High School. [1] He received his BS in Biology from the Massachusetts Institute of Technology in 1975 and completed his PhD in 1979 at the Massachusetts Institute of Technology, under the supervision of Nobel laureate David Baltimore. Ambros continued his research at MIT as the first postdoctoral fellow in the lab of future Nobel laureate H. Robert Horvitz. He became a faculty member at Harvard University in 1984 and moved to Dartmouth College in 1992. Ambros 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.

Discovery of microRNA

In 1993, Ambros and his co-workers Rosalind Lee and Rhonda Feinbaum reported in the journal Cell [2] 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, [3] [4] 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. However, the mechanism for control of LIN-14 remained unknown.

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. [5] Ambros and colleagues hypothesized 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.

In 2000, another C. elegans small RNA regulatory molecule, let-7, was characterized by the Ruvkun lab [6] and found to be conserved in many species, including vertebrates. [7] These discoveries confirmed that Ambros had in fact discovered a class of small RNAs with conserved functions. These molecules are now known as microRNA. Ambros was elected to the United States National Academy of Sciences in 2007. He was elected a Fellow of the American Academy of Arts and Sciences in 2011.

Awards

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

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

  1. Cleavage of mRNA strand into two pieces,
  2. Destabilization of mRNA by shortening its poly(A) tail, or
  3. Translation of mRNA into proteins.
<span class="mw-page-title-main">H. Robert Horvitz</span> American biologist

Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM is an American biologist best known for his research on the nematode worm Caenorhabditis elegans, for which he 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">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 University of Massachusetts Medical School 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 was identified from a study of developmental timing in C. elegans, and was later shown to be part of a much larger class of non-coding RNAs termed microRNAs. miR-98 microRNA precursor from human is a let-7 family member. Let-7 miRNAs have now been predicted or experimentally confirmed in a wide range of species (MIPF0000002). miRNAs are initially transcribed in long transcripts called primary miRNAs (pri-miRNAs), which are processed in the nucleus by Drosha and Pasha to hairpin structures of about 70 nucleotide. These precursors (pre-miRNAs) are exported to the cytoplasm by exportin5, where they are subsequently processed by the enzyme Dicer to a ~22 nucleotide mature miRNA. The involvement of Dicer in miRNA processing demonstrates a relationship with the phenomenon of RNA interference.

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 2017 he is a Royal Society Research Professor. From 2007 to 2020 he was Regius Professor of Botany in the Department of Plant Sciences at the University of Cambridge.

The Gruber Prize in Genetics, established in 2001, is one of three international awards worth US$500,000 made by the Gruber Foundation, a non-profit organization based at Yale University in New Haven, Connecticut.

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

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

Gary Bruce Ruvkun is an American molecular biologist at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston. Ruvkun discovered the mechanism by which lin-4, the first microRNA (miRNA) discovered by Victor Ambros, regulates the translation of target messenger RNAs via imperfect base-pairing to those targets, and discovered the second miRNA, let-7, and that it is conserved across animal phylogeny, including in humans. These miRNA discoveries revealed a new world of RNA regulation at an unprecedented small size scale, and the mechanism of that regulation. Ruvkun also discovered many features of insulin-like signaling in the regulation of aging and metabolism. He was elected a Member of the American Philosophical Society in 2019.

Cell Press is an all-science publisher of over 50 scientific journals across the life, physical, earth, and health sciences, both independently and in partnership with scientific societies. Many of Cell Press's journals are of high-quality. Cell Press was founded and is currently based in Cambridge, MA, and has offices across the United States, Europe, and Asia under its parent company Elsevier.

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.

In molecular biology mir-241 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

Junying Yuan is the Elizabeth D. Hay Professor of Cell Biology at Harvard Medical School, best known for her work in cell death. Early in her career, she contributed significant findings to the discovery and characterization of apoptosis. More recently, she was responsible for the discovery of the programmed form of necrotic cell death known as necroptosis.

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.

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References

  1. ↑ Gitschier, Jane (2010-03-05). "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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ "Newcomb Cleveland Prize Recipients". AAAS – The World's Largest General Scientific Society. 2013-07-05. Retrieved 2018-03-23.
  9. ↑ Fessenden, Jim (10 November 2014). "Victor Ambros awarded 2015 $3M Breakthrough Prize for co-discovery of microRNAs". UMass med NOW. University of Massachusetts Medical School. Retrieved 6 September 2015.
  10. ↑ "Victor Ambros awarded 2016 March of Dimes prize for co-discovery of MicroRNAs". University of Massachusetts Medical School. 3 May 2016. Retrieved 9 September 2016.
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