Gary Bruce Ruvkun (born March 26, 1952) is an American

molecular biologist Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is a teaching hospital located in the West End neighborhood of Boston, Massachusetts. It is the original and largest clinical education and research facility of Harvard Medical School/Harvar ...

and professor of

genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...

Harvard Medical School Harvard Medical School (HMS) is the medical school of Harvard University and is located in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Founded in 1782, HMS is the third oldest medical school in the Un ...

Boston Boston is the capital and most populous city in the Commonwealth (U.S. state), Commonwealth of Massachusetts in the United States. The city serves as the cultural and Financial centre, financial center of New England, a region of the Northeas ...

. Ruvkun discovered the mechanism by which '' lin-4'', the first

microRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) 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-transcr ...

(miRNA) discovered by

Victor Ambros Victor R. Ambros (born December 1, 1953) is an American developmental biologist who discovered the first known microRNA (miRNA). He is a professor at the University of Massachusetts Medical School. He completed both his undergraduate and doct ...

, 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 Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

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 Ageing (or aging in American English) is the process of becoming Old age, older until death. The term refers mainly to humans, many other animals, and fungi; whereas for example, bacteria, perennial plants and some simple animals are potentiall ...

and

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

. He was elected a Member of the

American Philosophical Society The American Philosophical Society (APS) is an American scholarly organization and learned society founded in 1743 in Philadelphia that promotes knowledge in the humanities and natural sciences through research, professional meetings, publicat ...

in 2019. Ruvkun was awarded the 2024

Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...

for the discovery of microRNA and its role in post-transcriptional gene regulation.

Early life and education

Ruvkun was born into a Jewish family, the son of Samuel and Dora (née Gurevich) Ruvkun. Ruvkun received a

Bachelor of Arts A Bachelor of Arts (abbreviated B.A., BA, A.B. or AB; from the Latin ', ', or ') is the holder of a bachelor's degree awarded for an undergraduate program in the liberal arts, or, in some cases, other disciplines. A Bachelor of Arts deg ...

(BA) with a major in

biophysics Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations ...

from the

University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California), is a Public university, public Land-grant university, land-grant research university in Berkeley, California, United States. Founded in 1868 and named after t ...

in 1973. He received a

Doctor of Philosophy A Doctor of Philosophy (PhD, DPhil; or ) is a terminal degree that usually denotes the highest level of academic achievement in a given discipline and is awarded following a course of Postgraduate education, graduate study and original resear ...

(PhD) in biophysics from

Harvard University Harvard University is a Private university, private Ivy League research university in Cambridge, Massachusetts, United States. Founded in 1636 and named for its first benefactor, the History of the Puritans in North America, Puritan clergyma ...

in 1982. He conducted his doctoral studies in the laboratory of Frederick M. Ausubel, where he investigated bacterial

nitrogen fixation Nitrogen fixation is a chemical process by which molecular dinitrogen () is converted into ammonia (). It occurs both biologically and abiological nitrogen fixation, abiologically in chemical industry, chemical industries. Biological nitrogen ...

genes. Ruvkun completed

postdoctoral research A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). Postdocs most commonly, but not always, have a temporary acade ...

with Robert Horvitz at the

Massachusetts Institute of Technology The Massachusetts Institute of Technology (MIT) is a Private university, private research university in Cambridge, Massachusetts, United States. Established in 1861, MIT has played a significant role in the development of many areas of moder ...

(MIT) and

Walter Gilbert Walter Gilbert (born March 21, 1932) is an American biochemist, physicist, molecular biology pioneer, and Nobel laureate. Education and early life Walter Gilbert was born in Boston, Massachusetts, on March 21, 1932, into a Jewish family, the so ...

of Harvard.

Research

miRNA ''lin-4''

Ruvkun's research revealed that the miRNA ''lin-4'', a 22 nucleotide regulatory RNA discovered in 1992 by

' 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. 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-14'' 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 Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

'' on the regulation of ''lin-14'' by ''lin-4''. In the same issue of ''Cell'',

described the regulatory product of ''lin-4'' as a small RNA. These papers revealed a new world of RNA regulation at an unprecedented small size scale, and the mechanism of that regulation. Together, this research is now recognized as the first description of

s and the mechanism by which partially base-paired miRNA::mRNA duplexes inhibit translation.

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. 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.

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, 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 RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...

and their paralogs, Dicer and the PIWI proteins, are used by both miRNAs and siRNAs. Ruvkun's lab in 2003 identified many more miRNAs, identified miRNAs from mammalian neurons, and in 2007 discovered many new protein-cofactors for miRNA function.

''C. elegans'' metabolism and longevity

Ruvkun's laboratory has also discovered that an insulin-like signaling pathway controls ''C. elegans'' metabolism and longevity. Klass Johnson and Kenyon 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. 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 genes that regulate aging and metabolism. Many of these genes are broadly conserved in animal phylogeny and could be targeted in diabetes drug development.

SETG: The Search for Extraterrestrial Genomes

The Ruvkun lab in collaboration with Maria Zuber at

MIT The Massachusetts Institute of Technology (MIT) is a private research university in Cambridge, Massachusetts, United States. Established in 1861, MIT has played a significant role in the development of many areas of modern technology and sc ...

, 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 ''

'' 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.

Microbial life beyond the Solar System

In 2019, Ruvkun, together with Chris Carr, Mike Finney and Maria Zuber, presented the argument that the appearance of sophisticated microbial life on Earth soon after it cooled, and the recent discoveries of

hot Jupiter Hot Jupiters (sometimes called hot Saturns) are a class of gas giant exoplanets that are inferred to be physically similar to Jupiter (i.e. Jupiter analogue, Jupiter analogues) but that have very short orbital periods (). The close proximity to t ...

s 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 The National Aeronautics and Space Administration (NASA ) is an independent agencies of the United States government, independent agency of the federal government of the United States, US federal government responsible for the United States ...

send a

DNA sequencer A DNA sequencer is a scientific instrument used to automate the DNA sequencing process. Given a sample of DNA, a DNA sequencer is used to determine the order of the four bases: G (guanine), C (cytosine), A (adenine) and T (thymine). This is then ...

Mars Mars is the fourth planet from the Sun. It is also known as the "Red Planet", because of its orange-red appearance. Mars is a desert-like rocky planet with a tenuous carbon dioxide () atmosphere. At the average surface level the atmosph ...

to search for life there in the hope that

evidence Evidence for a proposition is what supports the proposition. It is usually understood as an indication that the proposition is truth, true. The exact definition and role of evidence vary across different fields. In epistemology, evidence is what J ...

will be uncovered that life did not arise originally on Earth, but elsewhere in the universe.

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 and to the discovery of

microRNAs Micro ribonucleic acid (microRNA, miRNA, μRNA) 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-transcri ...

."Gary Ruvkun"
– ''The Gairdner Foundation'' (Retrieved on May 25, 2008) He is a recipient of the

Lasker Award In 1945 Albert Lasker and Mary Woodard Lasker created the Lasker Awards. Every year since then the award has been given to the living person considered to have made the greatest contribution to medical science or who has demonstrated public ser ...

for Basic Medical Research,"Gary Ruvkun"
– ''The Lasker Foundation'' (Retrieved on September 15, 2008) the Gairdner Foundation International Award, and the Benjamin Franklin Medal in Life Science. Ruvkun was elected as a member of the

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...

in 2008.

Awards

*2004 Rosenstiel Award for Distinguished Work in Medical Research of

Brandeis University Brandeis University () is a Private university, private research university in Waltham, Massachusetts, United States. It is located within the Greater Boston area. Founded in 1948 as a nonsectarian, non-sectarian, coeducational university, Bra ...

(co-recipient with Craig Mello, Andrew Fire and

) *2008 ''Warren Triennial Prize'',

(co-recipient with

) *2008 Gairdner Foundation International Award (co-recipient with

) *2008 Benjamin Franklin Medal in Life Science (co-recipient with

and

David Baulcombe Sir David Charles Baulcombe (born 7 April 1952) is a British plant scientist and geneticist. he was Head of Group, Gene Expression, in the Department of Plant Sciences at the University of Cambridge, and the Edward Penley Abraham Royal Socie ...

) *2008 Lasker Foundation Award for Basic Medical Research (co-recipient with

and

) *2008 Elected to the National Academy of Sciences *2009

Louisa Gross Horwitz Prize The Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers who have made an outstanding contribution in basic research in the fields of biology or biochemist ...

Columbia University Columbia University in the City of New York, commonly referred to as Columbia University, is a Private university, private Ivy League research university in New York City. Established in 1754 as King's College on the grounds of Trinity Churc ...

(co-recipient with

) *2009 American Academy of Arts and Sciences *2009

Massry Prize 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 biomedi ...

from the Keck School of Medicine,

University of Southern California The University of Southern California (USC, SC, or Southern Cal) is a Private university, private research university in Los Angeles, California, United States. Founded in 1880 by Robert M. Widney, it is the oldest private research university in ...

(co-recipient with

) *2009 Institute of Medicine *2011 The International

Dan David Prize The Dan David Prize is an international group of awards that recognize and support outstanding contributions to the study of history and other disciplines that shed light on the human past. Nine prizes of $300,000 are awarded each year to outstand ...

, awarded by

Tel Aviv University Tel Aviv University (TAU) is a Public university, public research university in Tel Aviv, Israel. With over 30,000 students, it is the largest university in the country. Located in northwest Tel Aviv, the university is the center of teaching and ...

, Israel (co-recipient with Cynthia Kenyon) *2012 Dr. Paul Janssen Award for Biomedical Research with

*2014 Wolf Prize for Medicine (co-recipient with

) *2015 Breakthrough Prize in Life Sciences (co-recipient with C. David Allis,

, Alim Louis Benabid, Jennifer A. Doudna and

Emmanuelle Charpentier Emmanuelle Marie Charpentier (; born 11 December 1968) is a French professor and researcher in microbiology, genetics, and biochemistry. As of 2015, she has been a director at the Max Planck Institute for Infection Biology in Berlin. In 2018, sh ...

). *2016 March of Dimes Prize in Developmental Biology (co-recipient with

) * 2023 Highly Ranked Scholar by ScholarGPS *2024

(co-recipient with

)

References

External links

*
RUVKUN LAB

Ruvkun Lab

Harvard Medical School faculty page
* – Gary Ruvkun, 2019. {{DEFAULTSORT:Ruvkun, Gary Living people American geneticists Biogerontologists Harvard Medical School faculty Recipients of the Albert Lasker Award for Basic Medical Research Members of the United States National Academy of Sciences 1952 births Massry Prize recipients Harvard Medical School alumni University of California, Berkeley alumni Members of the American Philosophical Society Members of the National Academy of Medicine Benjamin Franklin Medal (Franklin Institute) laureates Scientists from Berkeley, California Jewish American scientists American Nobel laureates Nobel laureates in Physiology or Medicine

Early life and education

Research

miRNA ''lin-4''

microRNA, ''let-7''

miRNAs and siRNAs

''C. elegans'' metabolism and longevity

SETG: The Search for Extraterrestrial Genomes

Innate immune surveillance

Microbial life beyond the Solar System

Published articles and recognition

Awards

See also

References

External links