Hildegard Lamfrom | |
---|---|
Born | |
Died | August 28, 1984 62) | (aged
Known for | protein translation |
Scientific career | |
Fields | biochemistry, molecular biology |
Institutions | Cedars of Lebanon Hospital, Carlsberg Laboratory, Caltech, MRC Laboratory, Intitut de Biologie Physico-Chimique, Institute of Molecular Biology in Eugene, Oregon, UCSD, Harvard Medical School |
Thesis | (1949) |
Doctoral advisor | Harry Goldblatt |
Hildegard Lamfrom was a German-American molecular biologist/biochemist. She helped develop one of the first in-vitro translation systems, using rabbit reticulocyte lysate to study protein synthesis (a process called translation) in a cell-free context. [1] This allowed her to make a number of contributions to the field including providing some of the first direct evidence for the existence of messenger RNA (mRNA) as a protein template, as well as the existence of polyribosomes (aka polysomes) (multiple ribosomes translating on the same mRNA). [2]
Lamfrom was born into a Jewish family in Augsburg, Germany, in 1922, the eldest of three sisters (Gertrude (Gert) Boyle and Eva). Her family fled Germany in 1937, when she was 15, and established themselves in Portland, Oregon. [3] Her father, who had owned a shirt factory in Germany bought a small hat and cap company that the family grew into Columbia Sportswear. [4] Her sister Gert Boyle would later run the company and become an entrepreneurial icon, later donating large amounts of money to cancer research in her sister's honor. [5]
Hiledgard graduated from Grant High School in Portland. [4] She then attended Reed College and financed her education by working in shipyards as a welder. [1] She earned a BA in biology from Reed and did research on avian malaria with Ralph Macy. [2] She then earned an MA from Oregon State University. [2] She was accepted to Western Reserve (now Case Western Reserve University)'s medical school, but decided to focus on research. [2] She studied the renin system with pathologist Harry Goldblatt at Case Western and earned her PhD in 1949. [2]
Lamfrom went with her PhD advisor Harry Goldblatt to Cedars of Lebanon Hospital in Los Angeles. [2] There, she continued to research the renin system for five more years. [1] In 1955 went to study at Copenhagen's Carlsberg Laboratory on an American Heart Association Fellowship, working in Linderstrom-Lang's department. [2] In 1958 she moved to Caltech where she did research with Henry Borsook. [2] Here at Caltech, with Richard Schweet, she was able to help work out an in vitro system for studying hemoglobin synthesis in rabbit reticulocyte lysate. [2] In this research, Hildegard was one of the first investigators to provide experimental evidence for the existence of messenger RNA, an informational molecule that directs the sequence of amino acids generated during protein synthesis. [6] From 1962 to 1965 she continued research on protein synthesis at the MRC Laboratory in Cambridge, England, working with Francis Crick and Sydney Brenner. [1] She then went to work at the Institut de Biologie Physico-Chimique in Paris (1965-1967). [1] She went on to collaborate with her close friend Anand Sarabhai at the Institute of Molecular Biology in Eugene, Oregon from 1967-1970. [1] The pair then researched in UCSD's chemistry department, where they collaborated with John Abelson to study tRNA synthesis. [1] In the 1970's Lamfrom and Sarabhai spent extended periods of time in India and established a research laboratory called Biocenter. [1] The last two years of her career were spent at Harvard Medical School, working with Tom Benjamin studying the involvement of middle T-antigen in tumor induction. [2]
The beginning of Lamfrom's career was spent studying the renin-antirenin system with pathologist Harry Goldblatt. [2] She then shifted to studying protein synthesis. Working with Richard Schweet at Caltech, and later with Paul Knopf at MRC, she helped develop one of the first in-vitro translation systems, using rabbit reticulocyte lysate to study protein synthesis (a process called translation) in a cell-free context. [1] This allowed her to make a number of contributions to the field. By mixing components of different animal cells, and showing that sheep ribosomes (protein-making complexes) could make rabbit hemoglobin and vice versa, she provided some of the first direct experimental evidence for the existence of messenger RNA and its role in determining what protein ribosomes make. [7] She also was one of the well as the existence of polyribosomes (aka polysomes) (multiple ribosomes translating on the same mRNA). [2] The last two years of her career were spent at Harvard Medical School, working with Tom Benjamin studying the involvement of middle T-antigen in tumor induction. [2]
Lamfrom met her life partner, Anand Sarabha, in India. [4] They hosted artisans, leading to unique collaborations. [1] Lamfrom died from a brain tumor after nine months of illness on August 28, 1984, in La Jolla, California. [1]
In 2015, Oregon Health & Science University (OHSU) named a biochemistry building in her honor. [8] OHSU's Knight Cancer Institute provides Hildegard Lamfrom Research Scholar Awards to early-stage cancer researchers, with funding from an endowment established by her nephew, Tim Boyle, CEO of Columbia Sportswear, and his wife Mary. [9] In 2010, her sister Gert Boyle gave an anonymous $100 million donation to the school in her sister's honor. [10] Gert, Tim and Mary Boyle, donated $2.5 million to create the Hildegard Lamfrom Endowed Chair in Basic Science at the OHSU Knight Cancer Institute. Hildegard is remembered as an influential mentor to young scientists, including Brian Druker. [11] In 2014, Tim and Mary donated $10 million to the Knight Cancer Institute at Oregon Health & Science University (OHSU) to create a mentorship fund in her honor. [12]
Protein biosynthesis is a core biological process, occurring inside cells, balancing the loss of cellular proteins through the production of new proteins. Proteins perform a number of critical functions as enzymes, structural proteins or hormones. Protein synthesis is a very similar process for both prokaryotes and eukaryotes but there are some distinct differences.
Ribosomes are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA (rRNA) molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.
In biology, translation is the process in living cells in which proteins are produced using RNA molecules as templates. The generated protein is a sequence of amino acids. This sequence is determined by the sequence of nucleotides in the RNA. The nucleotides are considered three at a time. Each such triple results in addition of one specific amino acid to the protein being generated. The matching from nucleotide triple to amino acid is called the genetic code. The translation is performed by a large complex of functional RNA and proteins called ribosomes. The entire process is called gene expression.
Marshall Warren Nirenberg was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" and describing how it operates in protein synthesis. In the same year, together with Har Gobind Khorana, he was awarded the Louisa Gross Horwitz Prize from Columbia University.
William French Anderson is an American physician, geneticist and molecular biologist. He is known as the "father of gene therapy". He graduated from Harvard College in 1958, Trinity College, Cambridge University (England) in 1960, and from Harvard Medical School in 1963. In 1990 he was the first person to succeed in carrying out gene therapy by treating a 4-year-old girl suffering from severe combined immunodeficiency. In 2006, he was convicted of sexual abuse of a minor and in 2007 was sentenced to 14 years in prison. He was paroled on May 17, 2018, for good behavior.
The Shine–Dalgarno (SD) sequence is a ribosomal binding site in bacterial and archaeal messenger RNA, generally located around 8 bases upstream of the start codon AUG. The RNA sequence helps recruit the ribosome to the messenger RNA (mRNA) to initiate protein synthesis by aligning the ribosome with the start codon. Once recruited, tRNA may add amino acids in sequence as dictated by the codons, moving downstream from the translational start site.
Oregon Health & Science University (OHSU) is a public research university focusing primarily on health sciences with a main campus, including two hospitals, in Portland, Oregon. The institution was founded in 1887 as the University of Oregon Medical Department and later became the University of Oregon Medical School. In 1974, the campus became an independent, self-governed institution called the University of Oregon Health Sciences Center, combining state dentistry, medicine, nursing, and public health programs into a single center. It was renamed Oregon Health Sciences University in 1981 and took its current name in 2001, as part of a merger with the Oregon Graduate Institute (OGI), in Hillsboro. The university has several partnership programs including a joint PharmD Pharmacy program with Oregon State University in Corvallis.
Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins. Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins by mass.
Sir Richard Timothy Hunt, is a British biochemist and molecular physiologist. He was awarded the 2001 Nobel Prize in Physiology or Medicine with Paul Nurse and Leland H. Hartwell for their discoveries of protein molecules that control the division of cells. While studying fertilized sea urchin eggs in the early 1980s, Hunt discovered cyclin, a protein that cyclically aggregates and is depleted during cell division cycles.
The Columbia Sportswear Company is an American company that manufactures and distributes outerwear, sportswear, and footwear, as well as headgear, camping equipment, ski apparel, and outerwear accessories.
Gertrude Boyle was a German-born American businesswoman in the U.S. state of Oregon. After her family fled Nazi Germany, her father founded the business that became Columbia Sportswear, where in 1970, she became company president. She remained president until 1988 and additionally, was chairwoman of the company's board of directors from 1983 until her death in 2019. Starting in the 1980s, she appeared in a series of advertisements for Columbia Sportswear with her son, Timothy Boyle, often humorously testing the quality and durability of their products. She was also a philanthropist and memoirist.
60S ribosomal protein L7 is a protein that in humans is encoded by the RPL7 gene.
The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that function to unwind double-stranded RNA.
Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.
Marilyn S. Kozak is an American professor of biochemistry at the Robert Wood Johnson Medical School. She was previously at the University of Medicine and Dentistry of New Jersey before the school was merged. She was awarded a PhD in microbiology by Johns Hopkins University studying the synthesis of the Bacteriophage MS2, advised by Daniel Nathans. In her original faculty job proposal, she sought to study the mechanism of eukaryotic translation initiation, a problem long thought to have already been solved by Joan Steitz. While in the Department of Biological Sciences at University of Pittsburgh, she published a series of studies that established the scanning model of translation initiation and the Kozak consensus sequence. Her current research interests are unknown as her last publication was in 2008.
Sir Hugh Reginald Brentnall Pelham, is a cell biologist who has contributed to our understanding of the body's response to rises in temperature through the synthesis of heat shock proteins. He served as director of the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) between 2006 and 2018.
Polysome profiling is a technique in molecular biology that is used to study the association of mRNAs with ribosomes. It is important to note that this technique is different from ribosome profiling. Both techniques have been reviewed and both are used in analysis of the translatome, but the data they generate are at very different levels of specificity. When employed by experts, the technique is remarkably reproducible: the 3 profiles in the first image are from 3 different experiments.
The OHSU Knight Cancer Institute is a research institute within Oregon Health & Science University. The National Cancer Institute (NCI) designated cancer center is led by director Brian Druker. It is the only NCI-designated Comprehensive Cancer Center in the state of Oregon. The institute is named after Phil Knight and his wife, who donated over $600 million to the center; $100 million in 2008 and $500 million in 2013. The $500 million gift required a matching $500 million, which led to a $100 million donation by Columbia Sportswear chairwoman Gert Boyle in 2014.
Mary Locke Petermann was an American cellular biochemist known for her key role in the discovery and characterization of animal ribosomes, the molecular complexes that carry out protein synthesis. She was the first woman to become a full professor at Cornell University's medical school.
Charles Daniel Lane is a British molecular biologist who along with colleagues Gerard Marbaix and John Gurdon discovered the oocyte exogenous mRNA expression system – a system that not only reveals aspects of the control of gene expression but also provides a "living test tube" for the study of macromolecules: such a whole cell system also shows the merits of a non-reductionist approach, and the possibility of mRNA therapeutics.
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