Mario Capecchi | |
---|---|
Born | Mario Ramberg Capecchi October 6, 1937 Verona, Italy |
Nationality | Italian, American |
Alma mater | Antioch College Harvard University |
Known for | Hox genes in knockout mice |
Awards | Kyoto Prize (1996) Franklin Medal (1997) Albert Lasker Award for Basic Medical Research (2001) Massry Prize (2002) Wolf Prize in Medicine (2002) Nobel Prize in Physiology or Medicine (2007) |
Scientific career | |
Fields | Genetics |
Institutions | Harvard Medical School University of Utah |
Thesis | On the Mechanism of Suppression and Polypeptide Chain Initiation (1967) |
Doctoral advisor | James D. Watson |
Website | capecchi |
Mario Ramberg Capecchi (born 6 October 1937) is an Italian-born molecular geneticist and a co-awardee of the 2007 Nobel Prize in Physiology or Medicine for discovering a method to create mice in which a specific gene is turned off, known as knockout mice. [1] [2] [3] [4] [5] [6] He shared the prize with Martin Evans and Oliver Smithies. [7] He is currently Distinguished Professor of Human Genetics and Biology at the University of Utah School of Medicine. [8] [9] [10] [11] [12]
Mario Capecchi was born in Verona, Italy, as the only child of Luciano Capecchi and Lucy Ramberg, an Italian-born [13] daughter of American-born Impressionist painter Lucy Dodd Ramberg and German archaeologist Walter Ramberg. His parents weren't married, and due to the chaos in Europe caused by World War II, the story of his early life is remarkable, but the details are unclear. In 1941 he and his mother were living near Bolzano, about 160 miles north of his father in Reggio Emilia when his mother was arrested and deported for pamphleteering and belonging to an anti-Fascist group. [14] Prior to her arrest [15] she had made contingency plans by selling her belongings and giving the proceeds to a nearby peasant family to care for her child. However, it was not long before Mario ended up on the streets of Bolzano. [16] [17] In July 1942, a few months before his fifth birthday, Italian records suggest he was reunited with his father in Reggio Emilia, which Mario did confirm but stated that he stayed with his father for only for a few brief periods [18] and that he mostly lived on the streets until he was placed in an orphanage towards the end of the war.
Mario almost died of malnutrition. His mother survived the war in Germany (part of the reason the details of his early life are unclear is that she would never talk about her experiences), and when it ended she began a year-long search for him. She finally found him on his ninth birthday in a hospital bed in Reggio Emilia ill with a fever and subsisting on a daily bowl of chicory coffee and bread crust. She took him to Rome, where he had his first bath since he had left her care and where, with money sent by his uncle, Edward Ramberg, an American physicist at RCA, they made arrangements to depart to the United States. He and his mother moved to Pennsylvania to live at an "intentionally cooperative community" called Bryn Gweled, [19] which had been co-founded by his uncle. (Capecchi's other maternal uncle, Walter Ramberg, was also a prominent American physicist [20] ). He graduated from George School, a Quaker boarding school in Bucks County, Pennsylvania, in 1956. [15]
Capecchi received his Bachelor of Science in chemistry and physics in 1961 from Antioch College in Ohio. Capecchi came to MIT as a graduate student intending to study physics and mathematics, [21] but during the course of his studies, he became interested in molecular biology. His change of interest was driven by the preference of working with few scientists and conducting experiments that did not require the use of big machines. He subsequently transferred to Harvard to join the lab of James D. Watson, co-discoverer of the structure of DNA. [22] Capecchi received his PhD in biophysics in 1967 [23] from Harvard University, with his doctoral thesis completed under the tutelage of Watson.
Capecchi was a Junior Fellow of the Society of Fellows at Harvard University from 1967 to 1969. In 1969 he became an assistant professor in the Department of Biochemistry at Harvard Medical School. He was promoted to associate professor in 1971. In 1973 he joined the faculty at the University of Utah. Since 1988 Capecchi has also been an investigator of the Howard Hughes Medical Institute. He is a member of the National Academy of Sciences. He has given a talk for Duke University's Program in Genetics and Genomics as part of their Distinguished Lecturer Series. [24] He was the speaker for the 2010 Racker Lectures in Biology & Medicine and Cornell Distinguished Lecture in Cell and Molecular Biology at Cornell University. [25] He is a member of the Italy-USA Foundation.
After the Nobel committee publicly announced that Capecchi was awarded the Nobel prize, an Austrian woman named Marlene Bonelli claimed that Capecchi was her long-lost half-brother. [26] In May 2008, Capecchi met with Bonelli, then 69, in northern Italy, and confirmed that she was his sister. [27]
Capecchi was awarded the Nobel prize for creating a knockout mouse. This is a mouse, created by genetic engineering and in vitro fertilization, in which a particular gene has been turned off. [28] For this work, Capecchi was awarded the 2007 Nobel prize for medicine or physiology, along with Martin Evans and Oliver Smithies, who also contributed.
Capecchi has also pursued a systematic analysis of the mouse Hox gene family. This gene family plays a key role in the control of embryonic development in all multicellular animals. They determine the placement of cellular development in the proper order along the axis of the body from head to toe.
Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM is an American biologist whose research on the nematode worm Caenorhabditis elegans 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".
Richard Axel is an American molecular biologist and university professor in the Department of Neuroscience at Columbia University and investigator at the Howard Hughes Medical Institute. His work on the olfactory system won him and Linda Buck, a former postdoctoral research scientist in his group, the Nobel Prize in Physiology or Medicine in 2004.
Joseph Leonard Goldstein ForMemRS is an American biochemist. He received the Nobel Prize in Physiology or Medicine in 1985, along with fellow University of Texas Southwestern researcher, Michael Brown, for their studies regarding cholesterol. They discovered that human cells have low-density lipoprotein (LDL) receptors that remove cholesterol from the blood and that when LDL receptors are not present in sufficient numbers, individuals develop hypercholesterolemia and become at risk for cholesterol related diseases, notably coronary heart disease. Their studies led to the development of statin drugs.
Sir Martin John EvansFLSW is an English biologist who, with Matthew Kaufman, was the first to culture mice embryonic stem cells and cultivate them in a laboratory in 1981. He is also known, along with Mario Capecchi and Oliver Smithies, for his work in the development of the knockout mouse and the related technology of gene targeting, a method of using embryonic stem cells to create specific gene modifications in mice. In 2007, the three shared the Nobel Prize in Physiology or Medicine in recognition of their discovery and contribution to the efforts to develop new treatments for illnesses in humans.
Oliver Smithies was a British-American geneticist and physical biochemist. He is known for introducing starch as a medium for gel electrophoresis in 1955, and for the discovery, simultaneously with Mario Capecchi and Martin Evans, of the technique of homologous recombination of transgenic DNA with genomic DNA, a much more reliable method of altering animal genomes than previously used, and the technique behind gene targeting and knockout mice. He received the Nobel Prize in Physiology or Medicine in 2007 for his genetics work.
Rudolf Jaenisch is a Professor of Biology at MIT and a founding member of the Whitehead Institute for Biomedical Research. He is a pioneer of transgenic science, in which an animal’s genetic makeup is altered. Jaenisch has focused on creating genetically modified mice to study cancer, epigenetic reprogramming and neurological diseases.
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Gene targeting is a biotechnological tool used to change the DNA sequence of an organism. It is based on the natural DNA-repair mechanism of Homology Directed Repair (HDR), including Homologous Recombination. Gene targeting can be used to make a range of sizes of DNA edits, from larger DNA edits such as inserting entire new genes into an organism, through to much smaller changes to the existing DNA such as a single base-pair change. Gene targeting relies on the presence of a repair template to introduce the user-defined edits to the DNA. The user will design the repair template to contain the desired edit, flanked by DNA sequence corresponding (homologous) to the region of DNA that the user wants to edit; hence the edit is targeted to a particular genomic region. In this way Gene Targeting is distinct from natural homology-directed repair, during which the ‘natural’ DNA repair template of the sister chromatid is used to repair broken DNA. The alteration of DNA sequence in an organism can be useful in both a research context – for example to understand the biological role of a gene – and in biotechnology, for example to alter the traits of an organism.
Conditional gene knockout is a technique used to eliminate a specific gene in a certain tissue, such as the liver. This technique is useful to study the role of individual genes in living organisms. It differs from traditional gene knockout because it targets specific genes at specific times rather than being deleted from beginning of life. Using the conditional gene knockout technique eliminates many of the side effects from traditional gene knockout. In traditional gene knockout, embryonic death from a gene mutation can occur, and this prevents scientists from studying the gene in adults. Some tissues cannot be studied properly in isolation, so the gene must be inactive in a certain tissue while remaining active in others. With this technology, scientists are able to knockout genes at a specific stage in development and study how the knockout of a gene in one tissue affects the same gene in other tissues.
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In molecular cloning and biology, a gene knock-in refers to a genetic engineering method that involves the one-for-one substitution of DNA sequence information in a genetic locus or the insertion of sequence information not found within the locus. Typically, this is done in mice since the technology for this process is more refined and there is a high degree of shared sequence complexity between mice and humans. The difference between knock-in technology and traditional transgenic techniques is that a knock-in involves a gene inserted into a specific locus, and is thus a "targeted" insertion. It is the opposite of gene knockout.
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