crème de la crème

Jai Ganesh · 2025-02-16 16:13:54

2164) Paul L. Modrich

Gist:

Life

Paul Modrich was born and raised in Raton, New Mexico, USA. His father was a biology teacher and encouraged his curiosity in nature. Modrich received his doctorate at Stanford University in 1973 and also studied at the Massachusetts Institute of Technology. Since 1976 he works at Duke University, Durham, North Carolina. He is also affiliated with Howard Hughes Medical Institute, Chevy Chase, Maryland.

Work

Living cells have DNA molecules that carry an organism's genes. For the organism to live and develop, its DNA cannot change. DNA molecules are not completely stable, and they can be damaged. In 1989, through studies of bacterial viruses, Modrich showed how methyl groups attached to the DNA molecule act as signals for repairing incorrect replications of DNA. These discoveries have increased our understanding of how the living cell works, the causes of cancer and about aging processes.

Summary

Paul Modrich (born 1946, Raton, New Mexico, U.S.) is an American biochemist who discovered mismatch repair, a mechanism by which cells detect and correct errors that are introduced into DNA during DNA replication and cell division. Modrich was among the first to show that a common form of inherited colorectal cancer is due to defective mismatch repair. For his contributions to the understanding of DNA repair and its role in human disease, Modrich received the 2015 Nobel Prize for Chemistry (shared with Swedish biochemist Tomas Lindahl and Turkish-American biochemist Aziz Sancar).

Modrich received a bachelor’s degree in biology in 1968 from the Massachusetts Institute of Technology and a Ph.D. in biochemistry in 1973 from Stanford University. In 1976, following postdoctoral studies at Harvard Medical School, he went to Duke University, where he joined the faculty as an assistant professor, and in 1988 he was named James B. Duke Professor of Biochemistry.

As a graduate student at Stanford, Modrich investigated an enzyme called ligase and its ability to catalyze the joining together of nucleotides in the DNA of the bacterium Escherichia coli. He found that ligase enzymes are essential to normal DNA synthesis in E. coli and hence are fundamental to the bacterium’s survival. In the late 1970s, intrigued by DNA lesions and the process of DNA replication, Modrich began to examine base-pair mismatches in E. coli DNA that are acquired during homologous recombination (the exchange of genetic material between two identical or nearly identical strands of DNA during DNA replication). By the early 1980s he had developed an assay to analyze mismatched base pairs. The development facilitated his subsequent identification and characterization of proteins and events involved in methyl-directed mismatch repair in E. coli, in which the absence of methyl groups on newly synthesized daughter strands of DNA serves as the signal for the initiation of mismatch repair.

In the early 1990s Modrich described the excision mechanism by which mismatched DNA is targeted and eliminated in E. coli cells. He also elucidated the mechanism of mismatch repair in human cells, revealing key similarities to the mechanism used by bacteria. He later uncovered a role for mismatch repair deficiency in hereditary nonpolyposis colon cancer (Lynch syndrome)—the most prevalent type of hereditary colorectal malignancy in humans—as well as in certain neurodegenerative conditions, such as Huntington disease.

Modrich was elected to the U.S. National Academy of Sciences in 1993 and the following year became a Howard Hughes Medical Institute Investigator. He was a fellow of the American Academy of Arts and Sciences from 2004.

Details

Paul Lawrence Modrich (born June 13, 1946) is an American biochemist, James B. Duke Professor of Biochemistry at Duke University and Investigator at the Howard Hughes Medical Institute. He is known for his research on DNA mismatch repair. Modrich received the Nobel Prize in Chemistry 2015, jointly with Aziz Sancar and Tomas Lindahl.

Early life and education

Modrich was born on June 13, 1946, in Raton, New Mexico to Laurence Modrich and Margaret McTurk. He has a younger brother Dave. His father was a biology teacher and coach for basketball, football and tennis at Raton High School where he graduated in 1964. Modrich is of Croatian, Montenegrin, German and Scottish (Gaelic)]origin. His paternal grandfather, of Croatian descent, is probably from the small village of Modrići near Zadar, and grandmother of Montenegrin descent, both immigrated to the United States from coastal Croatia in the late 19th century. His maternal family is of mixed German and Scotch-Irish descent. Modrich married fellow scientist Vickers Burdett in 1980.

Modrich obtained a B.S. degree from the Massachusetts Institute of Technology in 1968 and subsequently a Ph.D. degree from Stanford University in 1973. He continued his research as a postdoc in the lab of Charles C. Richardson at Harvard Medical School for a year (1973–1974).

Research

Modrich became an assistant professor at the chemistry department of University of California, Berkeley in 1974. He joined Duke University's faculty in 1976 and has been a Howard Hughes Investigator since 1995. He works primarily on strand-directed mismatch repair. His lab demonstrated how DNA mismatch repair serves as a copyeditor to prevent errors from DNA polymerase. Matthew Meselson previously proposed the existence of recognition of mismatches. Modrich performed biochemical experiments to study mismatch repair in E. coli. They later searched for proteins associated with mismatch repair in humans.

Jai Ganesh · 2025-02-17 15:40:31

2165) Aziz Sancar

Gist:

Life

Aziz Sancar was born in Savur in southeast Turkey in a lower middle class family. His parents had no education but considered education important for their children. Sancar studied at Istanbul University and at the University of Texas, Dallas, where his received his doctorate in 1977. He is a professor at the University of North Carolina School of Medicine, Chapel Hill. Aziz Sancar is married to Gwen Boles Sancar who also is a professor in biochemistry and biophysics.

Work

Living cells have DNA molecules that carry an organism's genes. For the organism to live and develop, its DNA cannot change. DNA molecules are not completely stable, and they can be damaged. In 1983, through studies of bacteria, Aziz Sancar showed how certain protein molecules, certain repair enzymes, repair DNA damaged by ultraviolet (UV) light. These discoveries have increased our understanding of how the living cell works, the causes of cancer and aging processes.

Summary

Aziz Sancar (born September 8, 1946, Savur, Mardin, Turkey) is a Turkish-American biochemist who contributed to mechanistic discoveries underlying a cellular process known as nucleotide excision repair, whereby cells correct errors in DNA that arise as a result of exposure to ultraviolet (UV) light or certain mutation-inducing chemicals. For his discoveries pertaining to mechanisms of DNA repair, Sancar received the 2015 Nobel Prize for Chemistry (shared with Swedish biochemist Tomas Lindahl and American biochemist Paul Modrich).

Sancar received an M.D. in 1969 from the Istanbul Medical School and subsequently worked as a local physician near Savur. In 1973 he went to the United States to study molecular biology at the University of Texas, Dallas, where four years later he completed a Ph.D. He then accepted a position as a research associate at Yale University and in 1982 joined the faculty at the University of North Carolina School of Medicine, where he later was named the Sarah Graham Kenan Professor of Biochemistry and Biophysics.

As a graduate student, Sancar studied an enzyme known as DNA photolyase in the bacterium Escherichia coli. At the time, the enzyme had been recently found to mediate the process of photoreactivation, whereby visible light induces enzymatic reactions that repair DNA damaged by UV irradiation. After moving to Yale, Sancar turned his attention to several other DNA repair factors in E. coli, namely the genes uvrA, uvrB, and uvrC. He purified the genes and reconstituted them in vitro (“in glass,” or outside a living organism), leading to his discovery of the excision repair function of an enzyme known as uvrABC nuclease (excision nuclease, or excinuclease) in E. coli. The enzyme specifically targeted DNA that had been damaged by UV or chemical exposure, cutting the affected DNA strand at each end of the damaged region and thereby enabling the removal of the damaged nucleotides.

Sancar and his colleagues later reconstituted a human excision nuclease, identified components required for nucleotide excision repair in human cells, and proposed that human cells employed additional enzymes in the removal of the excised portion of DNA. He also identified a role for defective nucleotide excision repair in the production of neurological abnormalities associated with xeroderma pigmentosum, a neurodegenerative condition that predisposes individuals to skin cancer. Abnormalities in nucleotide excision repair also were found to underlie other rare hereditary disorders, including math syndrome (characterized by multisystemic effects, such as dwarfism and photosensitivity) and photosensitive trichothiodystrophy (characterized by sulfur-deficient brittle hair, developmental abnormalities, and extreme sensitivity to ultraviolet light with normal skin cancer risk).

From the early 1980s Sancar continued to investigate photolyase in E. coli, and later he began to explore DNA damage checkpoints. He discovered two light-harvesting chromophores in photolyase, which he proposed were key components of the photolyase reaction mechanism and its activity at the blue end of the visible light spectrum. In the early 2000s he directly observed, for the first time, the mechanism of DNA repair by photolyase. Sancar also investigated human photolyase orthologs (genes evolutionarily related to E. coli DNA photolyase) known as cryptochrome 1 and 2. He found that the cryptochromes, which are located in the eye, function as photoreceptive components of the mammalian circadian clock.

Sancar was an elected member of multiple academies, including the American Academy of Arts and Sciences (2004), the U.S. National Academy of Sciences (2005), and the Turkish Academy of Sciences (2006).

Details

Aziz Sancar (born 8 September 1946) is a Turkish molecular biologist specializing in DNA repair, cell cycle checkpoints, and circadian clock. In 2015, he was awarded the Nobel Prize in Chemistry along with Tomas Lindahl and Paul L. Modrich for their mechanistic studies of DNA repair. He has made contributions on photolyase and nucleotide excision repair in bacteria that have changed his field.

Sancar is currently the Sarah Graham Kenan Professor of Biochemistry and Biophysics at the University of North Carolina School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. He is the co-founder of the Aziz & Gwen Sancar Foundation, which is a non-profit organization to promote Turkish culture and to support Turkish students in the United States.

Early life

Aziz Sancar was born on 8 September 1946 to a lower-middle-class family in the Savur district of Mardin Province, southeastern Turkey. His oldest brother Kenan Sancar is a retired brigadier general in the Turkish Armed Forces. He is the second cousin of the politician Mithat Sancar, who is a member of parliament from and chairman of HDP. He is the seventh of eight children.

His parents were uneducated; however, they put great emphasis on his education. He was educated by idealistic teachers who received their education in the Village Institutes, he later stated that this was a great inspiration to him. Throughout his school life, Sancar had great academic success that was noted by his teachers. He wanted to study chemistry whilst at high school, but was persuaded to study medicine after five of his classmates also got into medicine along with him. As such, he studied medicine at the Faculty of Medicine of Istanbul University.

Origins

According to his own account, he spoke Arabic with his parents and Turkish with his siblings. However, when asked about his origins, Sancar only underlined his Turkish nationality. Still, his cousin, Mithat Sancar, mentioned that their family is of Arab origins. Aziz Sancar's brother Tahir claimed in an interview that their family descended from Oghuz Turks from Central Asia, also mentioning that they are idealists. During his years at Istanbul University, he was involved with the Turkish nationalist organization Idealist Hearths (Ülkü Ocakları).

Education

Sancar received his primary education near his hometown of Savur. He then completed his MD degree in Istanbul University of Turkey in 1969 and he graduated from school as the top student. He completed his PhD degree on the photoreactivating enzyme of E. coli in 1977 at The University of Texas at Dallas in the laboratory of Claud Stan Rupert, now Professor Emeritus.

Career

Sancar is an honorary member of the Turkish Academy of Sciences and the American Academy of Arts and Sciences.

After graduating from Istanbul University, Sancar returned to Savur. Although he wanted to go to the United States, he was recommended to try out being a doctor, and he worked as a doctor in the region for 1.5 years. He then won a scholarship from TÜBİTAK to pursue further education in biochemistry at Johns Hopkins University, but returned to Savur in 1973 as a doctor after spending 1.5 years there due to having social difficulties and inability to adapt to the American way of life. He only spoke French when he arrived in the US, but learned English during his education at Johns Hopkins.

Soon after, he wrote to Rupert, who had been involved in the discovery of DNA repair and was at Johns Hopkins during Sancar's time there but had since moved to the University of Texas at Dallas. He was accepted and completed his PhD in molecular biology there. His interest had been stimulated by the recovery of bacteria, which had been exposed to deadly amounts of ultraviolet radiation, upon their illumination with blue light. In 1976, as part of his doctoral dissertation, he managed to replicate the gene for photolyase, an enzyme that repairs thymine dimers that result from ultraviolet damage.

After completing his PhD, Sancar had three rejected applications for postdoctoral positions and then took up work at Yale University as a laboratory technician. He worked at Yale for five years. Here, he started his field-changing work on nucleotide excision repair, another DNA mechanism that works in the dark. In the laboratory of Dean Rupp, he elucidated the molecular details of this process, identifying UvrABC endonuclease and the genes that code for it, and furthermore discovering that these enzymes cut twice on the damaged strand of DNA, removing 12–13 nucleotides that include the damaged part.

Following his mechanistic elucidations of nucleotide exchange repair, he was accepted as a lecturer at the University of North Carolina, the only university that he got a positive response from out of the 50 he applied to. He has stated that his accent of English was detrimental to his career as a lecturer. At Chapel Hill, Sancar discovered the following steps of nucleotide excision repair in bacteria and worked on the more complex version of this repair mechanism in humans.

His longest-running study has involved photolyase and the mechanisms of photo-reactivation. In his inaugural article in the PNAS, Sancar captured the photolyase radicals he has chased for nearly 20 years, thus providing direct observation of the photocycle for thymine dimer repair.

Aziz Sancar was elected to the National Academy of Sciences in 2005 as the first Turkish member. He is the Sarah Graham Kenan Professor of Biochemistry, at the University of North Carolina at Chapel Hill. He is married to Gwen Boles Sancar, who graduated the same year and who is also a professor of Biochemistry and Biophysics at the University of North Carolina at Chapel Hill. Together, they founded Carolina Türk Evi, a permanent Turkish Center in close proximity to the campus of UNC-CH, which provides graduate housing for four Turkish researchers at UNC-CH, short term guest services for Turkish visiting scholars, and a center for promoting Turkish-American interchange.

Research on circadian clock

Sancar and his research team have discovered that two genes, Period and Cryptochrome, keep the circadian clocks of all human cells in proper rhythm, syncing them to the 24 hours of the day and seasons. Their findings were published in the Genes and Development journal on September 16, 2014. Sancar's research has provided a complete understanding of the workings of Circadian clocks in humans, which may be used to treat a wide range of different illnesses and disorders such as jet-lag and seasonal affective disorder, and may be useful in controlling and optimizing various cancer treatments.

Personal life

Sancar is married to Gwen Boles Sancar, with whom he met during his PhD in Dallas, where she was also studying molecular biology. They got married in 1978.

Sancar is a practicing Muslim. In an interview, he stated: "I am proud to be Muslim, but I can not state this fact in many regions of the United States due to ongoing issues." In the immediate aftermath of being awarded the Nobel Prize, his ethnicity was questioned in social media. Sancar said he was "disturbed by some of the questions he received," particularly by questions about his ethnic background. When asked as to whether he is "a Turk or half-Arab" by the BBC, Aziz Sancar responded: "I told them that I neither speak Arabic nor Kurdish and that I was a Turk," he said. "I'm a Turk, that's it." Aziz Sancar's brother Tahir informed in an interview that their family descended from Oghuz Turks who once migrated from Central Asia. He also said that his brother's Nobel Prize was an honor for all of Turkey, including the Kurds.

In an interview, Sancar stated that in his youth, he was an idealist but he didn't participate in activities. In another interview, Sancar stated that he supports moderate Pan-Turkism. On September 26, 2021, Sancar was the honorary guest of the Turkic Council on occasion of the meeting of the foreign secretaries from member states and has given a presentation titled "Knowledge and the National Awakening of the Turkic World", as announced by Turkish Minister of Foreign Affairs Mevlüt Çavuşoğlu.

Awards
He was awarded the 2015 Nobel Prize in Chemistry along with Tomas Lindahl and Paul L. Modrich for their mechanistic studies of DNA repair. He was granted Presidential Young Investigator Award from the National Science Foundation in Molecular Biophysics in 1984. Sancar is the second Turkish Nobel laureate after Orhan Pamuk, who is also an alumnus of Istanbul University.

Aziz Sancar donated his original Nobel Prize golden medal and certificate to the mausoleum of Mustafa Kemal Atatürk, with a presidential ceremony on 19 May 2016, which is the 97th anniversary of Atatürk initiating the Turkish War of Independence. He delivered a replica of his Nobel medal and certificate to Istanbul University, from which he earned his MD.

On January 19, 2025, during a ceremony held at the Sancar Cultural Center in the state of North Carolina, USA, TÜRKSOY General Secretary Sultan Raev presented Sancar with the Order of Cultural Ambassador of the Turkic World.

Jai Ganesh · Yesterday 16:52:26

2166) William C. Campbell (scientist)

Gist:

Life

William C. Campbell was born in Ramelton, Ireland. He studied at Trinity College at the University of Dublin and at the University of Wisconsin, Madison, USA, where he earned his doctorate in 1957. He then worked for the pharmaceutical company Merck at its Institute for Therapeutic Research until 1990. He is now affiliated with Drew University, Madison, New Jersey i USA.

Work

A number of serious infectious diseases are caused by parasites spread by insects. River blindness is caused by a tiny worm that can infect the cornea and cause blindness. Lymphatic filariasis, or elephantiasis, is also caused by a worm and produces chronic swelling. Satoshi Omura cultured bacteria, which produce substances that inhibit the growth of other microorganisms. In 1978 he succeeded in culturing a strain from which William Campbell purified a substance, avermectin, which in a chemically modified form, ivermectin, proved effective against river blindness and elephantiasis.

Summary

William Campbell (born June 28, 1930, Ramelton, Ireland) is an Irish-born American parasitologist known for his contribution to the discovery of the anthelmintic compounds avermectin and ivermectin, which proved vital to the control of certain parasitic infections in humans and other animals. For his discoveries, Campbell was awarded the 2015 Nobel Prize for Physiology or Medicine (shared with Japanese microbiologist Ōmura Satoshi and Chinese scientist Tu Youyou).

Campbell earned a bachelor’s degree in zoology from Trinity College in Dublin in 1952. He subsequently went to the United States, where he studied veterinary science, zoology, and pathology at the University of Wisconsin. In 1957, after completing a Ph.D. at Wisconsin, Campbell took a position as a research assistant at the Merck Institute for Therapeutic Research in New Jersey. There in 1976 he was made the director of basic parasitology, and from 1984 to 1990 he served as a senior scientist and directed assay research and development. Campbell became a U.S. citizen in 1962.

In the 1970s researchers at Merck & Co. received a culture of the soil bacterium Streptomyces avermitilis from Ōmura Satoshi, who had discovered the species in the course of his work at the Kitasato Institute in Japan. Preliminary experiments suggested that the organism produced a substance that was potentially lethal to certain types of parasites. In 1975, using an assay that tested compounds for activity against the infectious nematode Nematospiroides dubius in mice, Campbell and colleagues at Merck discovered avermectin, which existed as several compounds, all closely related in structure and known as macrocyclic lactones. Having purified avermectin, the Merck team subjected the compound to structural modification, ultimately producing a chemical known as ivermectin. Ivermectin was found to be active against a wide array of microfilariae (larvae) produced by certain threadlike nematode parasites. Of particular consequence was its ability to clear infections in humans involving the microfilariae of Onchocerca volvulus, the cause of river blindness, and Wuchereria bancrofti and Brugia malayi, the major causes of lymphatic filariasis (elephantiasis). Both river blindness and lymphatic filariasis were significant sources of debilitating illness in tropical regions of the world. The drug also proved critical to the prevention of certain arthropod and microfilariae-associated infections in other animals, including horses, sheep, and cattle; it also was used widely for the prevention of heartworm disease in cats and dogs.

In later research Campbell studied a variety of parasitic diseases, including trichinosis. He retired as research fellow emeritus at Drew University in New Jersey. During his career he served as the president of multiple organizations, including the American Society of Parasitologists. In addition to numerous research papers, Campbell edited two texts, Trichinella and Trichinosis (1983) and Chemotherapy of Parasitic Diseases (1986, with Robert S. Rew), which were critical to furthering the understanding of parasitic disease.

Details

William Cecil Campbell (born 28 June 1930) is an Irish-American microbiologist known for his work in discovering a novel therapy against infections caused by roundworms, for which he was jointly awarded the 2015 Nobel Prize in Physiology or Medicine. He helped to discover a class of drugs called avermectins, whose derivatives have been shown to have "extraordinary efficacy" in treating River blindness and Lymphatic filariasis, among other parasitic diseases affecting animals and humans. Campbell worked at the Merck Institute for Therapeutic Research 1957–1990, and has become a research fellow emeritus at Drew University.

Biography

Campbell was born in Ramelton, County Donegal, Ireland in 1930, the third son of R. J. Campbell, a farm supplier. He studied at Trinity College, Dublin with James Desmond Smyth, graduating in 1952 with first class honours in Zoology. He then attended the University of Wisconsin–Madison on a Fulbright Scholarship, earning his PhD degree in 1957 for work on the liver fluke, a parasite affecting sheep.

From 1957 to 1990 Campbell worked at Merck Institute for Therapeutic Research,[8] and from 1984 to 1990 he was a Senior Scientist and Director with Assay Research and Development. He became a US citizen in 1964. One of his discoveries while at Merck was the fungicide thiabendazole, used to treat potato blight, historically a scourge of Ireland. Thiabendazole is also used to treat trichinosis in humans.

Campbell is best known for his work on parasitic diseases. Japanese microbiologist Satoshi Ōmura isolated and cultured many varieties of natural soil-based bacteria from the group Streptomyces. Campbell led a team at Merck in studying Ōmura's cultures and examining their effectiveness in treating parasites in domestic and farm animals. From a sample of Streptomyces avermitilis, naturally occurring in soil, he derived a macrocyclic lactone. After further modification, it was named ivermectin (generic) or Mectizan.

In 1978, having identified a successful treatment for a type of worms affecting horses, Campbell realised that similar treatments might be useful against related types of worms that affect humans. In 1981, Merck carried out successful Phase 1 treatment trials in Senegal and France on river blindness. Taken orally, the drug paralyses and sterilises the parasitic worm that causes the illness. Merck went on to study the treatment of elephantiasis. The research of Satoshi Ōmura, William Campbell, and their co-workers created a new class of drugs for the treatment of parasites.

In 1987, Merck decided to donate Ivermectin (Mectizan) to developing countries. Campbell was instrumental in that decision. With the World Health Organization they created an "unprecedented" drug donation program, with the intention of wiping out river blindness. As of 2001 an estimated 25 million people were being treated each year, in a total of 33 countries in sub-Saharan Africa, Latin America, and the Middle East. As of 2013, the Carter Center's International Task Force for Disease Eradication independently verified that the disease had been eradicated in Colombia, Ecuador, and Mexico.

The greatest challenge for science is to think globally, think simply and act accordingly. It would be disastrous to neglect the diseases of the developing world. One part of the world affects another part. We have a moral obligation to look after each other, but we're also naturally obligated to look after our own needs. It has to be both.

From 1990 to 2010, when he retired, Campbell was a research fellow at Drew University in Madison, N.J., where he supervised undergraduate research and taught courses in parasitology. He has written about the history of parasitology in Antarctic exploration, including the work of surgeon Edward L. Atkinson in Scott's ill-fated Terra Nova Expedition.

In 2002, Campbell was elected member of the United States National Academy of Sciences. In 2015, he and Satoshi Ōmura shared half of the 2015 Nobel Prize in Physiology or Medicine for their research on therapies against infections caused by roundworm parasites, using derivatives of avermectin. Campbell is the seventh Irish person to be awarded a Nobel Prize, including Ernest Walton who was awarded the Nobel Prize in Physics in 1951 and Samuel Beckett for Literature in 1968.

Personal life

William C. Campbell is married to Mary Mastin Campbell. He is a published poet and painter. His recreational activities include table tennis and kayaking.

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#1701 2025-02-16 16:13:54

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#1702 2025-02-17 15:40:31

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