Victor Ambros

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Victor Ambros
Victor Ambros.jpg
Victor Ambros (Photo: Jane Gitschier)
Born 1953[1]
Hanover, New Hampshire
Known for discovery of the first known microRNA

Victor Ambros 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.

Background[edit]

Ambros was born in New Hampshire and grew up in Vermont. He completed his PhD 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.

Discovery of microRNA[edit]

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][7] and found to be conserved in many species, including vertebrates.[8] These discoveries confirmed that Ambros had in fact discovered a class of small RNAs with conserved sequence and functions. These molecules are now known as microRNA. In recognition of his discovery, Ambros received the Gairdner Foundation International Award and the Albert Lasker Award for Basic Medical Research in 2008.[9] He is also the 2008 co-recipient of the Benjamin Franklin Medal in Life Science.[10] 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[edit]

References[edit]

  1. ^ Victor R. Ambros - The Franklin Institute Awards - Laureate Database
  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.  edit
  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.  edit
  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.  edit
  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.  edit
  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.  edit
  7. ^ Slack, F. J.; Basson, M.; Liu, Z.; Ambros, V.; Horvitz, H. R.; Ruvkun, G. (2000). "The lin-41 RBCC gene acts in the C. Elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor". Molecular Cell 5 (4): 659–669. doi:10.1016/S1097-2765(00)80245-2. PMID 10882102.  edit
  8. ^ 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. doi:10.1038/35040556. PMID 11081512.  edit
  9. ^ "Victor Ambros"The Gairdner Foundation (Retrieved on May 25, 2008)
  10. ^ Franklin Award
  11. ^ AAAS Newcomb Cleveland Prize recipients