Gary Ruvkun

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Gary Bruce Ruvkun (born March 1952, Berkeley, California) [1] is an American molecular biologist at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston. [2] 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.

Contents

Education

Ruvkun obtained his undergraduate degree in 1973 at the University of California, Berkeley. His PhD work was done at Harvard University in the laboratory of Frederick M. Ausubel, where he investigated bacterial nitrogen fixation genes. Ruvkun completed post-doctoral studies with Robert Horvitz at the Massachusetts Institute of Technology (MIT) and Walter Gilbert of Harvard. [3]

Research

mRNA lin-4

Ruvkun's research revealed that the miRNA lin-4, a 22 nucleotide regulatory RNA discovered in 1992 by Victor Ambros' lab, regulates its target mRNA lin-14 by forming imperfect RNA duplexes to down-regulate translation. The first indication that the key regulatory element of the lin-14 gene recognized by the lin-4 gene product was in the lin-14 3’ untranslated region came from the analysis of lin-14 gain-of-function mutations which showed that they are deletions of conserved elements in the lin-14 3’ untranslated region. Deletion of these elements relieves the normal late stage-specific repression of LIN-14 protein production, and lin-4 is necessary for that repression by the normal lin-14 3' untranslated region. [4] [5] In a key breakthrough, the Ambros lab discovered that lin-4 encodes a very small RNA product, defining the 22 nucleotide miRNAs. When Ambros and Ruvkun compared the sequence of the lin-4 miRNA and the lin-14 3’ untranslated region, they discovered that the lin-4 RNA base pairs with conserved bulges and loops to the 3’ untranslated region of the lin-14 target mRNA, and that the lin-14 gain of function mutations delete these lin-4 complementary sites to relieve the normal repression of translation by lin-4. In addition, they showed that the lin-14 3' untranslated region could confer this lin-4-dependent translational repression on unrelated mRNAs by creating chimeric mRNAs that were lin-4-responsive. In 1993, Ruvkun reported in the journal Cell on the regulation of lin-14 by lin-4. [6] In the same issue of Cell, Victor Ambros described the regulatory product of lin-4 as a small RNA [7] These papers revealed a new world of RNA regulation at an unprecedented small size scale, and the mechanism of that regulation. [8] [9] Together, this research is now recognized as the first description of microRNAs and the mechanism by which partially base-paired miRNA::mRNA duplexes inhibit translation. [10]

microRNA, let-7

In 2000, the Ruvkun lab reported the identification of second C. elegans microRNA, let-7, which like the first microRNA regulates translation of the target gene, in this case lin-41, via imperfect base pairing to the 3’ untranslated region of that mRNA. [11] [12] This was an indication that miRNA regulation via 3’ UTR complementarity may be a common feature, and that there were likely to be more microRNAs. The generality of microRNA regulation to other animals was established by the Ruvkun lab later in 2000, when they reported that the sequence and regulation of the let-7 microRNA is conserved across animal phylogeny, including in humans. [13] Presently thousands of miRNAs have been discovered, pointing to a world of gene regulation at this size regime.

miRNAs and siRNAs

When siRNAs of the same 21-22 nucleotide size as lin-4 and let-7 were discovered in 1999 by Hamilton and Baulcombe in plants, [14] the fields of RNAi and miRNAs suddenly converged. It seemed likely that the similarly sized miRNAs and siRNAs would use similar mechanisms. In a collaborative effort, the Mello and Ruvkun labs showed that the first known components of RNA interference and their paralogs, Dicer and the PIWI proteins, are used by both miRNAs and siRNAs. [15] Ruvkun's lab in 2003 identified many more miRNAs, [16] [17] identified miRNAs from mammalian neurons, [18] and in 2007 discovered many new protein-cofactors for miRNA function. [19] [20] [21]

C. elegans metabolism and longevity

Ruvkun's laboratory has also discovered that an insulin-like signaling pathway controls C. elegans metabolism and longevity. Klass [22] Johnson [23] and Kenyon [24] showed that the developmental arrest program mediated by mutations in age-1 and daf-2 increase C. elegans longevity. The Ruvkun lab established that these genes constitute an insulin like receptor and a downstream phosphatidylinositol kinase that couple to the daf-16 gene product, a highly conserved Forkhead transcription factor. Homologues of these genes have now been implicated in regulation of human aging. [25] These findings are also important for diabetes, since the mammalian orthologs of daf-16 (referred to as FOXO transcription factors) are also regulated by insulin. The Ruvkun lab has used full genome RNAi libraries to discover a comprehensive set of genes that regulate aging and metabolism. Many of these genes are broadly conserved in animal phylogeny and are likely to reveal the neuroendocrine system that assesses and regulates energy stores and assigns metabolic pathways based on that status.

SETG: The Search for Extraterrestrial Genomes

Since 2000, the Ruvkun lab in collaboration with Maria Zuber at MIT, Chris Carr (now at Georgia Tech), and Michael Finney (now a San Francisco biotech entrepreneur) has been developing protocols and instruments that can amplify and sequence DNA and RNA to search for life on another planet that is ancestrally related to the Tree of Life on Earth. The Search for Extraterrestrial Genomes, or SETG, project has been developing a small instrument that can determine DNA sequences on Mars (or any other planetary body), and send the information in those DNA sequence files to Earth for comparison to life on Earth.

Innate immune surveillance

In 2012, Ruvkun made an original contribution to the field of immunology with the publication of a featured paper in the journal Cell describing an elegant mechanism for innate immune surveillance in animals that relies on the monitoring of core cellular functions in the host, which are often sabotaged by microbial toxins during the course of infection. [26]

Microbial life beyond the Solar System

In 2019, Ruvkun, together with Chris Carr, Mike Finney and Maria Zuber, [27] presented the argument that the appearance of sophisticated microbial life on Earth soon after it cooled, and the recent discoveries of Hot Jupiters and disruptive planetary migrations in exoplanet systems favors the spread of DNA-based microbial life across the galaxy. The SETG project is working to have NASA send a DNA sequencer to Mars to search for life there in the hope that evidence will be uncovered that life did not arise originally on Earth, but elsewhere in the universe. [28]

Published articles and recognition

As of 2018, Ruvkun has published about 150 scientific articles. Ruvkun has received numerous awards for his contributions to medical science, for his contributions to the aging field [29] and to the discovery of microRNAs. [30] He is a recipient of the Lasker Award for Basic Medical Research, [31] the Gairdner Foundation International Award, and the Benjamin Franklin Medal in Life Science. [32] Ruvkun was elected as a member of the National Academy of Sciences in 2008.

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.

Small temporal RNA regulates gene expression during roundworm development by preventing the mRNAs they bind from being translated. In contrast to siRNA, stRNAs downregulate expression of target RNAs after translation initiation without affecting mRNA stability. Nowadays, stRNAs are better known as miRNAs.

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.

mir-103/107 microRNA precursor

The miR-103 microRNA precursor, is a short non-coding RNA gene involved in gene regulation. miR-103 and miR-107 have now been predicted or experimentally confirmed in human.

mir-9/mir-79 microRNA precursor family

The miR-9 microRNA, is a short non-coding RNA gene involved in gene regulation. The mature ~21nt miRNAs are processed from hairpin precursor sequences by the Dicer enzyme. The dominant mature miRNA sequence is processed from the 5' arm of the mir-9 precursor, and from the 3' arm of the mir-79 precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In vertebrates, miR-9 is highly expressed in the brain, and is suggested to regulate neuronal differentiation. A number of specific targets of miR-9 have been proposed, including the transcription factor REST and its partner CoREST.

mir-10 microRNA precursor family

The mir-10 microRNA precursor is a short non-coding RNA gene involved in gene regulation. It is part of an RNA gene family which contains mir-10, mir-51, mir-57, mir-99 and mir-100. mir-10, mir-99 and mir-100 have now been predicted or experimentally confirmed in a wide range of species. miR-51 and miR-57 have currently only been identified in the nematode Caenorhabditis elegans.

mir-1 microRNA precursor family

The miR-1 microRNA precursor is a small micro RNA that regulates its target protein's expression in the cell. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give products at ~22 nucleotides. In this case the mature sequence comes from the 3' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In humans there are two distinct microRNAs that share an identical mature sequence, and these are called miR-1-1 and miR-1-2.

mir-92 microRNA precursor family

The miR-92 microRNAs are short single stranded non-protein coding RNA fragments initially discovered incorporated into an RNP complex with a proposed role of processing RNA molecules and further RNP assembly. Mir-92 has been mapped to the human genome as part of a larger cluster at chromosome 13q31.3, where it is 22 nucleotides in length but exists in the genome as part of a longer precursor sequence. There is an exact replica of the mir-92 precursor on the X chromosome. MicroRNAs are endogenous triggers of the RNAi pathway which involves several ribonucleic proteins (RNPs) dedicated to repressing mRNA molecules via translation inhibition and/or induction of mRNA cleavage. miRNAs are themselves matured from their long RNA precursors by ribonucleic proteins as part of a 2 step biogenesis mechanism involving RNA polymerase 2.

<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">Victor Ambros</span> American developmental biologist (born 1953)

Victor R. 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.

<span class="mw-page-title-main">Daf-16</span> Ortholog

DAF-16 is the sole ortholog of the FOXO family of transcription factors in the nematode Caenorhabditis elegans. It is responsible for activating genes involved in longevity, lipogenesis, heat shock survival and oxidative stress responses. It also protects C.elegans during food deprivation, causing it to transform into a hibernation - like state, known as a Dauer. DAF-16 is notable for being the primary transcription factor required for the profound lifespan extension observed upon mutation of the insulin-like receptor DAF-2. The gene has played a large role in research into longevity and the insulin signalling pathway as it is located in C. elegans, a successful ageing model organism.

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.

<span class="mw-page-title-main">Julie Ahringer</span> American geneticist

Julie Ann Ahringer is an American/British Professor of Genetics and Genomics, Director of the Gurdon Institute and a member of the Department of Genetics at the University of Cambridge. She leads a research lab investigating the control of gene expression.

In bioinformatics, TargetScan is a web server that predicts biological targets of microRNAs (miRNAs) by searching for the presence of sites that match the seed region of each miRNA. For many species, other types of sites, known as 3'-compensatory sites are also identified. These miRNA target predictions are regularly updated and improved by the laboratory of David Bartel in conjunction with the Whitehead Institute Bioinformatics and Research Computing Group.

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.

References

  1. ↑ Who's Who in America 66th edition. Vol 2: M–Z. Marquis Who's Who, Berkeley Heights 2011, p. 3862
  2. ↑ Nair, P. (2011). "Profile of Gary Ruvkun". Proceedings of the National Academy of Sciences. 108 (37): 15043–5. Bibcode:2011PNAS..10815043N. doi: 10.1073/pnas.1111960108 . PMC   3174634 . PMID   21844349.
  3. ↑ Harvard Medical School faculty page
  4. ↑ Arasu, P.; Wightman, B.; Ruvkun, G. (1991). "Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28". Genes & Development. 5 (10): 1825–1833. doi: 10.1101/gad.5.10.1825 . PMID   1916265.
  5. ↑ Wightman, B.; Bürglin, T. R.; Gatto, J.; Arasu, P.; Ruvkun, G. (1991). "Negative regulatory sequences in the lin-14 3'-untranslated region are necessary to generate a temporal switch during Caenorhabditis elegans development". Genes & Development. 5 (10): 1813–1824. doi: 10.1101/gad.5.10.1813 . PMID   1916264.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ Ruvkun, G; Wightman, B; Bürglin, T; Arasu, P (1991). "Dominant gain-of-function mutations that lead to misregulation of the C. Elegans heterochronic gene lin-14, and the evolutionary implications of dominant mutations in pattern-formation genes". Development. Supplement. 1: 47–54. PMID   1742500.
  9. ↑ Ruvkun, G.; Ambros, V.; Coulson, A.; Waterston, R.; Sulston, J.; Horvitz, H. R. (1989). "Molecular Genetics of the Caenorhabditis Elegans Heterochronic Gene Lin-14". Genetics. 121 (3): 501–516. doi:10.1093/genetics/121.3.501. PMC   1203636 . PMID   2565854.
  10. ↑ Ruvkun, G.; Wightman, B.; Ha, I. (2004). "The 20 years it took to recognize the importance of tiny RNAs". Cell. 116 (2 Suppl): S93–S96, 2 S96 following S96. doi: 10.1016/S0092-8674(04)00034-0 . PMID   15055593. S2CID   17490257.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ Hamilton, A. J.; Baulcombe, D. C. (1999). "A species of small antisense RNA in posttranscriptional gene silencing in plants". Science. 286 (5441): 950–952. doi:10.1126/science.286.5441.950. PMID   10542148.
  15. ↑ Grishok, A.; Pasquinelli, A. E.; Conte, D.; Li, N.; Parrish, S.; Ha, I.; Baillie, D. L.; Fire, A.; Ruvkun, G.; Mello, C. C. (2001). "Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. Elegans developmental timing". Cell. 106 (1): 23–34. doi: 10.1016/S0092-8674(01)00431-7 . PMID   11461699. S2CID   6649604.
  16. ↑ Grad, Y.; Aach, J.; Hayes, G. D.; Reinhart, B. J.; Church, G. M.; Ruvkun, G.; Kim, J. (2003). "Computational and experimental identification of C. Elegans microRNAs". Molecular Cell. 11 (5): 1253–1263. doi: 10.1016/S1097-2765(03)00153-9 . PMID   12769849.
  17. ↑ Parry, D.; Xu, J.; Ruvkun, G. (2007). "A whole-genome RNAi Screen for C. Elegans miRNA pathway genes". Current Biology. 17 (23): 2013–2022. doi:10.1016/j.cub.2007.10.058. PMC   2211719 . PMID   18023351.
  18. ↑ Kim, J.; Krichevsky, A.; Grad, Y.; Hayes, G.; Kosik, K.; Church, G.; Ruvkun, G. (2004). "Identification of many microRNAs that copurify with polyribosomes in mammalian neurons". Proceedings of the National Academy of Sciences of the United States of America. 101 (1): 360–365. Bibcode:2004PNAS..101..360K. doi: 10.1073/pnas.2333854100 . PMC   314190 . PMID   14691248.
  19. ↑ Hayes, G.; Frand, A.; Ruvkun, G. (2006). "The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25". Development. 133 (23): 4631–4641. doi: 10.1242/dev.02655 . PMID   17065234.
  20. ↑ Hayes, G.; Ruvkun, G. (2006). "Misexpression of the Caenorhabditis elegans miRNA let-7 is sufficient to drive developmental programs". Cold Spring Harbor Symposia on Quantitative Biology. 71: 21–27. doi: 10.1101/sqb.2006.71.018 . PMID   17381276.
  21. ↑ Pierce, M.; Weston, M.; Fritzsch, B.; Gabel, H.; Ruvkun, G.; Soukup, G. (2008). "MicroRNA-183 family conservation and ciliated neurosensory organ expression". Evolution & Development. 10 (1): 106–113. doi:10.1111/j.1525-142X.2007.00217.x. PMC   2637451 . PMID   18184361.
  22. ↑ Klass, M.; Hirsh, D. (1976). "Non-ageing developmental variant of Caenorhabditis elegans". Nature. 260 (5551): 523–525. Bibcode:1976Natur.260..523K. doi:10.1038/260523a0. PMID   1264206. S2CID   4212418.
  23. ↑ Friedman, D. B.; Johnson, T. E. (1988). "A Mutation in the Age-1 Gene in Caenorhabditis Elegans Lengthens Life and Reduces Hermaphrodite Fertility". Genetics. 118 (1): 75–86. doi:10.1093/genetics/118.1.75. PMC   1203268 . PMID   8608934.
  24. ↑ Kenyon, C.; Chang, J.; Gensch, E.; Rudner, A.; Tabtiang, R. (1993). "A C. Elegans mutant that lives twice as long as wild type". Nature. 366 (6454): 461–464. Bibcode:1993Natur.366..461K. doi:10.1038/366461a0. PMID   8247153. S2CID   4332206.
  25. ↑ Kenyon, C. J. (2010). "The genetics of ageing". Nature. 464 (7288): 504–512. Bibcode:2010Natur.464..504K. doi:10.1038/nature08980. PMID   20336132. S2CID   2781311.
  26. ↑ Melo, Justine A.; Ruvkun, Gary (April 13, 2012). "Inactivation of conserved C. elegans genes engages pathogen- and xenobiotic-associated defenses". Cell. 149 (2): 452–466. doi:10.1016/j.cell.2012.02.050. ISSN   1097-4172. PMC   3613046 . PMID   22500807.
  27. ↑ Ruvkun, Gary (April 17, 2019). "YouTube Video (24:32) – Breakthrough Discuss 2019 – What is True for E. coli on Earth Will Be True for Life on Proxima Centauri b". University of Berkeley . Retrieved July 9, 2019.
  28. ↑ Chotiner, Isaac (July 8, 2019). "What If Life Did Not Originate on Earth?". The New Yorker . ISSN   0028-792X . Retrieved July 9, 2019.
  29. ↑ "Dan David Prize 10th Anniversary 2011 Laureates Announced: The Coen Brothers – for Cinema; Marcus Feldman – for Evolution; Cynthia Kenyon and Gary Ruvkun – for Ageing". www.newswire.ca. Retrieved April 25, 2018.
  30. ↑ "Gary Ruvkun" Archived May 12, 2008, at the Wayback Machine – The Gairdner Foundation (Retrieved on May 25, 2008)
  31. ↑ "Gary Ruvkun" Archived July 16, 2010, at the Wayback Machine – The Lasker Foundation (Retrieved on September 15, 2008)
  32. ↑ "Franklin Award". Archived from the original on May 15, 2008. Retrieved December 14, 2021.
  33. ↑ "Victor Ambros awarded 2016 March of Dimes prize for co-discovery of MicroRNAs". University of Massachusetts Medical School. May 3, 2016. Retrieved September 9, 2016.
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