H. Robert Horvitz

Last updated
H. Robert Horvitz
H. Robert Horvitz.jpg
Horvitz in 2003
Born
Howard Robert Horvitz

(1947-05-08) May 8, 1947 (age 76) [1]
Chicago, Illinois, US
Alma mater
Known for Apoptosis research
Spouse Martha Constantine-Paton
Awards
Scientific career
Fields Biology
Institutions MRC Laboratory of Molecular Biology
Massachusetts Institute of Technology
Thesis Modifications of the host RNA polymerase induced by coliphage T4  (1974)
Doctoral advisors Walter Gilbert
James D. Watson
Notable students Michael Hengartner

Gary Ruvkun Yishi Jin

Junying Yuan
Website web.mit.edu/horvitz/www/

Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM (born May 8, 1947) is an American biologist best known for his research on the nematode worm Caenorhabditis elegans , [4] [2] 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". [5]

Contents

Education and early life

Horvitz was born in Chicago, Illinois to Jewish parents, [1] the son of Mary R. (Savit), a school teacher, and Oscar Freedom Horvitz, a GAO accountant. He majored in mathematics at Massachusetts Institute of Technology, where he joined Alpha Epsilon Pi and spent his summers working for IBM, at first wiring panels for accounting machines and then in his final summer helping to develop IBM's Conversational Programming System. [2]

During his senior year, Horvitz took his first courses in biology and was encouraged by his professors to continue to study biology in graduate school, despite his limited coursework in the field. After he completed his undergraduate studies in 1968, he enrolled in graduate studies in biology at Harvard University, where he studied T4-induced modifications of E. coli RNA polymerase under the direction of Walter Gilbert and James Watson. He completed his PhD in 1974. [6]

Career

In 1974, Horvitz took a postdoctoral position at the Laboratory of Molecular Biology (LMB) in Cambridge, England, where he worked with his future Nobel prize co-winners Sydney Brenner and John Sulston on the genetics and cell lineage of C. elegans. In 1978, Horvitz was offered a faculty position at MIT, where he is currently Professor of Biology and a member of the McGovern Institute for Brain Research. He is also an Investigator of the Howard Hughes Medical Institute.[ citation needed ]

Horvitz serves as the chair of the board of trustees for Society for Science & the Public and is a member of the USA Science and Engineering Festival's Advisory Board. [7]

Research

At LMB, Horvitz worked with Sulston to track every non-gonadal cell division that occurred during larval development, and published a complete description of these lineages in 1977. [2] [8] Later, in cooperation with Sulston and Martin Chalfie, Horvitz began investigations first characterizing several cell lineage mutants [9] [10] and then seeking genes that controlled cell lineage or that controlled specific lineages. In 1981, they identified and characterized the gene lin-4 , a "heterochronic" mutant that changes the timeline of cell fates. [11]

In his early work at MIT, Horvitz continued his work on cell lineage and cell fate, using C. elegans to investigate whether there was a genetic program controlling cell death, or apoptosis. In 1986, he identified the first "death genes", ced-3 and ced-4. He showed that functional ced-3 and ced-4 genes were a prerequisite for cell death to be executed. [12] He went on to show that another gene, ced-9, protects against cell death by interacting with ced-4 and ced-3, as well as identifying a number of genes that direct how a dead cell is eliminated. Horvitz showed that the human genome contains a ced-3-like gene. [13] [14]

Horvitz's later research continued to use C. elegans to analyze the genetic control of animal development and behavior, as well as to link discoveries in the nematode to human diseases, particularly cancer and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). He made further advancements in defining the molecular pathway of programmed cell death, and has identified several key components, including: EGL-1, a protein which activates apoptosis by inhibiting CED-9; [15] transcription factors ces-1 and ces-2, [16] [17] and ced-8, which controls the timing of cell death. [18] He continued working on heterochronic mutants and other aspects of cell lineage, and established lines of research in signal transduction, morphogenesis, and neural development. Horvitz has collaborated with Victor Ambros and David Bartel on a project to characterize the complete set of the more than 100 microRNAs in the C. elegans genome. [19]

Works

Horvitz has over 255 publications, has been cited over 49,000 times and has an h-index of 108. [20]

Awards and honors

See also

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.

<span class="mw-page-title-main">Sydney Brenner</span> South African biologist and Nobel prize winner

Sydney Brenner was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston. Brenner made significant contributions to work on the genetic code, and other areas of molecular biology while working in the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, England. He established the roundworm Caenorhabditis elegans as a model organism for the investigation of developmental biology, and founded the Molecular Sciences Institute in Berkeley, California, United States.

<span class="mw-page-title-main">John Sulston</span> British biologist and academic (1942–2018)

Sir John Edward Sulston was a British biologist and academic who won the Nobel Prize in Physiology or Medicine for his work on the cell lineage and genome of the worm Caenorhabditis elegans in 2002 with his colleagues Sydney Brenner and Robert Horvitz at the MRC Laboratory of Molecular Biology. He was a leader in human genome research and Chair of the Institute for Science, Ethics and Innovation at the University of Manchester. Sulston was in favour of science in the public interest, such as free public access of scientific information and against the patenting of genes and the privatisation of genetic technologies.

<span class="mw-page-title-main">MRC Laboratory of Molecular Biology</span> Research institute in Cambridge, England

The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical research laboratory at the forefront of scientific discovery, dedicated to improving the understanding of key biological processes at atomic, molecular and cellular levels using multidisciplinary methods, with a focus on using this knowledge to address key issues in human health.

Apoptosis is the process of programmed cell death. From its early conceptual beginnings in the 1950s, it has exploded as an area of research within the life sciences community. As well as its implication in many diseases, it is an integral part of biological development.

John Graham White is an Emeritus Professor of Anatomy and Molecular Biology at the University of Wisconsin–Madison. His research interests are in the biology of the model organism Caenorhabditis elegans and laser microscopy.

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">Cornelia Bargmann</span> American neurobiologist

Cornelia Isabella "Cori" Bargmann is an American neurobiologist. She is known for her work on the genetic and neural circuit mechanisms of behavior using C. elegans, particularly the mechanisms of olfaction in the worm. She has been elected to the National Academy of Sciences and had been a Howard Hughes Medical Institute investigator at UCSF and then Rockefeller University from 1995 to 2016. She was the Head of Science at the Chan Zuckerberg Initiative from 2016 to 2022. In 2012 she was awarded the $1 million Kavli Prize, and in 2013 the $3 million Breakthrough Prize in Life Sciences.

Cell death abnormality gene 9 (CED-9), also known as apoptosis regulator CED-9, is a gene found in Caenorhabditis elegans that inhibits/represses programmed cell death (apoptosis). The gene was discovered while searching for mutations in the apoptotic pathway after the discovery of the apoptosis promoting genes CED-3 and CED-4. The gene gives rise to the apoptosis regulator CED-9 protein found as an Integral membrane protein in the mitochondrial membrane. The protein is homologous to the human apoptotic regulator Bcl-2 as well as all other proteins in the Bcl-2 protein family. CED-9 is involved in the inhibition of CED-4 which is the activator of the CED-3 caspase. Because of the pathway homology with humans as well as the specific protein homology, CED-9 has been used to represent the human cell apoptosis interactions of Bcl-2 in research.

<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.

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.

The nematode worm Caenorhabditis elegans was first studied in the laboratory by Victor Nigon and Ellsworth Dougherty in the 1940s, but came to prominence after being adopted by Sydney Brenner in 1963 as a model organism for the study of developmental biology using genetics. In 1974, Brenner published the results of his first genetic screen, which isolated hundreds of mutants with morphological and functional phenotypes, such as being uncoordinated. In the 1980s, John Sulston and co-workers identified the lineage of all 959 cells in the adult hermaphrodite, the first genes were cloned, and the physical map began to be constructed. In 1998, the worm became the first multi-cellular organism to have its genome sequenced. Notable research using C. elegans includes the discoveries of caspases, RNA interference, and microRNAs. Six scientists have won the Nobel prize for their work on C. elegans.

Judith Kimble is a Henry Vilas Professor of Biochemistry, Molecular Biology, Medical Genetics and Cell and Regenerative Biology at the University of Wisconsin–Madison and Investigator with the Howard Hughes Medical Institute (HHMI). Kimble’s research focuses on the molecular regulation of animal development.

<span class="mw-page-title-main">Cell lineage</span> Developmental history of a tissue or organ

Cell lineage denotes the developmental history of a tissue or organ from the fertilized embryo. This is based on the tracking of an organism's cellular ancestry due to the cell divisions and relocation as time progresses, this starts with the originator cells and finishing with a mature cell that can no longer divide.

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.

Ced-3 is one of the major protein components of the programmed cell death (PCD) pathway for Caenorhabditis elegans. There are in total 14 genes that are involved in programmed cell death, other important ones including ced-4 and ced-9 genes. The healthy nematode worm will require 131 somatic cell deaths out of the 1090 cells during the developmental stages. The gene initially encodes for a prototypical caspase (procaspase) where the active cysteine residue cleaves aspartate residues, thus becoming a functional caspase. Ced-3 is an executioner caspase that must dimerize with itself and be initiated by ced-4 in order to become active. Once active, it will have a series of reactions that will ultimately lead to the apoptosis of targeted cells.

Worm bagging is a form of vivipary observed in nematodes, namely Caenorhabditis elegans. The process is characterized by eggs hatching within the parent and the larvae proceeding to consume and emerge from the parent.

Abby F. Dernburg is a professor of Cell and Developmental Biology at the University of California, Berkeley, an Investigator of the Howard Hughes Medical Institute, and a Faculty Senior Scientist at Lawrence Berkeley National Laboratory.

Paul W. Sternberg is an American biologist. He does research for WormBase on C. elegans, a model organism.

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.

References

  1. 1 2 Green, David B. (May 8, 2015). "Biologist who discovered death genes' through worm research is born". This Day in Jewish History. Haaretz. Retrieved September 18, 2015.
  2. 1 2 3 4 H. Robert Horvitz on Nobelprize.org OOjs UI icon edit-ltr-progressive.svg , accessed 11 October 2020
  3. 1 2 "Fellows of the Royal Society". London: Royal Society. Archived from the original on 2015-03-16.
  4. ↑ Horvitz, H. Robert (May 30, 2012). "Genetic Control of Nematode Development and Behavior". Our scientists. Howard Hughes Medical Institute. Retrieved September 18, 2015.
  5. ↑ Press Release, nobelprize.org. Accessed February 28, 2024.
  6. ↑ "H. Robert Horvitz - Biographical". www.nobelprize.org. Retrieved 2016-01-26.
  7. ↑ "USA Science and Engineering Festival - Advisors". Usasciencefestival.org. Archived from the original on 2010-04-21. Retrieved 2013-04-23.
  8. ↑ Sulston, J.E.; Horvitz, H.R. (1977). "Post-embryonic Cell Lineages of the Nematode, Caenorhabditis elegans" (PDF). Developmental Biology. 56 (1): 110–156. doi:10.1016/0012-1606(77)90158-0. PMID   838129 . Retrieved 26 January 2016.
  9. ↑ Horvitz, H. R.; Sulston, J. E. (1980-10-01). "Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans". Genetics. 96 (2): 435–454. doi:10.1093/genetics/96.2.435. ISSN   0016-6731. PMC   1214309 . PMID   7262539.
  10. ↑ Sulston, John E.; Horvitz, H. Robert (1981-02-01). "Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans". Developmental Biology. 82 (1): 41–55. doi:10.1016/0012-1606(81)90427-9. PMID   7014288.
  11. ↑ Chalfie, M.; Horvitz, H. R.; Sulston, J. E. (1981-04-01). "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. ISSN   0092-8674. PMID   7237544. S2CID   33933388.
  12. ↑ Ellis, Hilary M.; Horvitz, H. Robert (1986-03-28). "Genetic control of programmed cell death in the nematode C. elegans". Cell. 44 (6): 817–829. doi:10.1016/0092-8674(86)90004-8. PMID   3955651. S2CID   44031839.
  13. ↑ Ellis, Ronald E.; Yuan, Junying; Horvitz, H. Robert (1991-01-01). "Mechanisms and Functions of Cell Death". Annual Review of Cell Biology. 7 (1): 663–698. doi:10.1146/annurev.cb.07.110191.003311. PMID   1809356.
  14. ↑ "MIT's Horvitz shares Nobel Prize in physiology". MIT News. Retrieved 2016-01-26.
  15. ↑ Conradt, B.; Horvitz, H. R. (1998-05-15). "The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9". Cell. 93 (4): 519–529. doi: 10.1016/s0092-8674(00)81182-4 . ISSN   0092-8674. PMID   9604928. S2CID   1668835.
  16. ↑ Metzstein, M. M.; Horvitz, H. R. (1999-09-01). "The C. elegans cell death specification gene ces-1 encodes a snail family zinc finger protein". Molecular Cell. 4 (3): 309–319. doi: 10.1016/s1097-2765(00)80333-0 . ISSN   1097-2765. PMID   10518212.
  17. ↑ Metzstein, Mark M.; Hengartner, Michael O.; Tsung, Nancy; Ellis, Ronald E.; Horvitz, H. Robert (1996-08-08). "Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2". Nature. 382 (6591): 545–547. Bibcode:1996Natur.382..545M. doi:10.1038/382545a0. PMID   8700229. S2CID   4307474.
  18. ↑ Stanfield, G. M.; Horvitz, H. R. (2000-03-01). "The ced-8 gene controls the timing of programmed cell deaths in C. elegans". Molecular Cell. 5 (3): 423–433. doi: 10.1016/s1097-2765(00)80437-2 . ISSN   1097-2765. PMID   10882128.
  19. ↑ "The Horvitz Laboratory". web.mit.edu. Retrieved 2016-01-26.
  20. ↑ "Web of Science". Thomson Reuters. Retrieved 19 September 2015.
  21. 1 2 3 "H. Robert Horvitz". The Gruber Foundation. Retrieved January 13, 2018.
  22. ↑ "NAS award in molecular biology". National Academy of Sciences. Retrieved 20 May 2016.
  23. ↑ "Horvitz receives Roche's Mattia Award". MIT News. Massachusetts Institute of Technology. November 3, 1993. Retrieved 17 October 2022.
  24. ↑ "Hans Sigrist Prize Winners". University of Bern. Retrieved 20 May 2016.
  25. ↑ "Rosenstiel Basic Medical Sciences Research Center - Past Winners". brandeis.edu. Brandeis University. Retrieved 17 October 2022.
  26. ↑ "recipients of the passano laureate and physician scientist awards". The Passano Foundation, Inc. Passano Foundation. Retrieved 17 October 2022.
  27. ↑ "In recognition of their pioneering contribution to our understanding of apoptosis". gairdner.org. the Canada Gairdner Foundation. Retrieved 17 October 2022.
  28. ↑ "Prize Winners of the Paul Ehrlich and Ludwig Darmstaedter Prize" (PDF). goethe-university-frankfurt.de. The Paul Ehrlich Foundation. Retrieved 17 October 2022.
  29. ↑ "MARCH OF DIMES PRIZE IN DEVELOPMENTAL BIOLOGY RECIPIENT LIST" (PDF). marchofdimes.org. Retrieved 17 October 2022.
  30. ↑ "Horwitz Prize Goes To MIT's Horvitz, Harvard's Korsmeyer". Columbia University Record. 26 (8). 30 October 2000. Retrieved 19 September 2015.
  31. ↑ "The Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research, 2001: H. Robert Horvitz, PhD". The Neuroscientist. 7 (6): 551. December 2001. doi:10.1177/107385840100700611. PMID   11765132. S2CID   41177724 . Retrieved 17 October 2022.
  32. ↑ "The 2001 Genetics Society of America Medal: H. Robert Horvitz". Genetics Society of America. Retrieved 17 October 2022.
  33. ↑ "H. Robert Horvits". Superstars of Science. Archived from the original on 2014-08-10. Retrieved 18 September 2015.
  34. ↑ "The Wiley Prize in Biomedical Sciences". John Wiley & Sons, Inc. Retrieved 17 October 2022.
  35. ↑ "2002 Genetics Prize: H. Robert Horvitz". Gruber prizes. The Gruber Foundation. Retrieved 20 May 2016.
  36. ↑ "American Philosophical Society Member History". amphilsoc.org.
  37. ↑ "Mendel Medal". The Genetics Society. Retrieved 17 October 2022.

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