Rosalind Lee | |
---|---|
Alma mater | Massachusetts Institute of Technology |
Known for | Discovery of microRNA |
Awards | Newcomb Cleveland Prize (2003) |
Scientific career | |
Institutions | Harvard University Dartmouth College UMass Chan Medical School |
Rosalind 'Candy' Lee is a biomedical scientist, best known for her breakthrough paper on the discovery of microRNA which was published in 1993. [1] In 2002, Lee was joint recipient of the Newcomb Cleveland Prize, for the best paper published in the journal Science that year. [2] In 2024, Lee's 1993 paper was cited as the seminal discovery for which the Nobel Prize in physiology or medicine was awarded that year, to co-author Victor Ambros, her husband. [3]
Lee graduated from Massachusetts Institute of Technology in 1976. [4] That same year, she married Victor Ambros, who was at that time a PhD student at MIT. [5]
Lee began working as a research assistant in Victor Ambros' lab in 1987. Her work on the cloning of lin-4 began in January, 1989, in Ambros's lab at Harvard University, and she was joined on the project in the fall of 1989 by Rhonda Feinbaum, a postdoc. [6] [7] Lee and Feinbaum worked for a couple of years in a labor-intensive search for a gene behind a mutation. [8] What they eventually discovered was microRNA, [9] adding a new mechanism for gene regulation. [10] [11] The 1993 paper was soon accepted for publication, and in a change of journal policy, it was published with a notice on the front page that it was jointly first-authored by Lee and Feinbaum, [6] clarifying that both contributed equally to the research. [12] In a 2004 paper, Lee, Feinbaum and Ambros describe how they eventually wrote up the work in 1993, and submitted it to the journal Cell , in parallel with a related paper by Gary Ruvkun. [6]
Lee's co-authored 1993 paper is widely regarded as the seminal contribution in the discovery of microRNA, for which her husband Ambros and Ruvkun were both awarded the Nobel Prize in 2024. [3] The Nobel announcement provoked interest into the question of why Lee hadn't also been recognized with the award. [12]
As of 2024, Lee is a Senior Scientist, in Program in Molecular Medicine, Dr. Victor Ambros's Molecular Medicine Laboratory, at UMass Chan Medical School. [13]
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.
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, according to Alfred Nobel's 1895 will, are awarded "to those who, during the preceding year, have conferred the greatest benefit to humankind". Nobel Prizes are awarded in the fields of Physics, Medicine or Physiology, Chemistry, Literature, and Peace.
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.
Micro ribonucleic acid 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-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in messenger RNA (mRNA) molecules, then silence said mRNA molecules by one or more of the following processes:
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".
Phillip Allen Sharp is an American geneticist and molecular biologist who co-discovered RNA splicing. He shared the 1993 Nobel Prize in Physiology or Medicine with Richard J. Roberts for "the discovery that genes in eukaryotes are not contiguous strings but contain introns, and that the splicing of messenger RNA to delete those introns can occur in different ways, yielding different proteins from the same DNA sequence". He has been selected to receive the 2015 Othmer Gold Medal.
Craig Cameron Mello is an American biologist and professor of molecular medicine at the University of Massachusetts Medical School in Worcester, Massachusetts. He was awarded the 2006 Nobel Prize for Physiology or Medicine, along with Andrew Z. Fire, for the discovery of RNA interference. This research was conducted at the Carnegie Institution of Washington and published in 1998. Mello has been a Howard Hughes Medical Institute investigator since 2000.
Andrew Zachary Fire is an American biologist and professor of pathology and of genetics at the Stanford University School of Medicine. He was awarded the 2006 Nobel Prize in Physiology or Medicine, along with Craig C. Mello, for the discovery of RNA interference (RNAi). This research was conducted at the Carnegie Institution of Washington and published in 1998.
Joan Elaine Argetsinger Steitz is Sterling Professor of Molecular Biophysics and Biochemistry at Yale University and Investigator at the Howard Hughes Medical Institute. She is known for her discoveries involving RNA, including ground-breaking insights into how ribosomes interact with messenger RNA by complementary base pairing and that introns are spliced by small nuclear ribonucleic proteins (snRNPs), which occur in eukaryotes. In September 2018, Steitz won the Lasker-Koshland Award for Special Achievement in Medical Science. The Lasker award is often referred to as the 'American Nobel' because 87 of the former recipients have gone on to win Nobel prizes.
The Let-7 microRNA precursor gives rise to let-7, a microRNA (miRNA) involved in control of stem-cell division and differentiation. let-7, short for "lethal-7", was discovered along with the miRNA lin-4 in a study of developmental timing in C. elegans, making these miRNAs the first ever discovered. let-7 was later identified in humans as the first human miRNA, and is highly conserved across many species. Dysregulation of let-7 contributes to cancer development in humans by preventing differentiation of cells, leaving them stuck in a stem-cell like state. let-7 is therefore classified as a tumor suppressor.
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.
Sir David Charles Baulcombe is a British plant scientist and geneticist. As of October 2024 he was Head of Group, Gene Expression, in the Department of Plant Sciences at the University of Cambridge, and the Edward Penley Abraham Royal Society Research Professor and Regius Professor of Botany Emeritus at Cambridge. He held the Regius botany chair in that department from 2007 to 2020.
Thomas Tuschl is a German biochemist and molecular biologist, known for his research on RNA.
Victor R. Ambros is an American developmental biologist and Nobel Laureate who discovered the first known microRNA (miRNA). He is a professor at the University of Massachusetts Medical School. He completed both his undergraduate and doctoral studies at the Massachusetts Institute of Technology. Ambros received the Nobel Prize in Physiology or Medicine in 2024 for his research on microRNA.
Gary Bruce Ruvkun is an American molecular biologist and Nobel laureate at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston.
MicroRNA sequencing (miRNA-seq), a type of RNA-Seq, is the use of next-generation sequencing or massively parallel high-throughput DNA sequencing to sequence microRNAs, also called miRNAs. miRNA-seq differs from other forms of RNA-seq in that input material is often enriched for small RNAs. miRNA-seq allows researchers to examine tissue-specific expression patterns, disease associations, and isoforms of miRNAs, and to discover previously uncharacterized miRNAs. Evidence that dysregulated miRNAs play a role in diseases such as cancer has positioned miRNA-seq to potentially become an important tool in the future for diagnostics and prognostics as costs continue to decrease. Like other miRNA profiling technologies, miRNA-Seq has both advantages and disadvantages.
In molecular biology mir-84 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
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 biomedical sciences. Shaul G. Massry, M.D., who established the Massry Foundation, is Professor Emeritus of Medicine and Physiology and Biophysics at the Keck School of Medicine, University of Southern California. He served as Chief of its Division of Nephrology from 1974 to 2000. In 2009 the KECK School of Medicine was asked to administer the Prize, and has done so since that time. Out of 25 prizes bestowed until 2021, fourteen were awarded to future Nobel Prize winners. No Massry Prize was awarded in 2020, 2022 and 2023.
NamiRNAs are a type of miRNAs present in the nucleus, which can activate gene expression by binding to the enhancer, and therefore were named nuclear activating miRNAs (NamiRNAs), such as miR-24-1 and miR-26. These miRNAs loci are enriched with epigenetic markers that display enhancer activity like histone H3K27ac, P300/CBP, and DNaseI high-sensitivity loci. These NamiRNAs are able to activate the related enhancers and co-work with them to up-regulate the expression of neighboring genes. NamiRNAs are able to promote global gene transcription by binding their targeted enhancers in whole genome level.
LIN-14 is a nuclear protein that plays a crucial role in regulating developmental timing in the nematode worm Caenorhabditis elegans. It functions as a heterochronic gene, controlling the timing of developmental events during larval development. LIN-14 protein levels are high at the beginning of the first larval stage (L1) and then rapidly decline, which is essential for the transition from early to late cell fates. LIN-14 is a BEN domain transcription factor, capable of binding DNA and directly regulating gene expression. The protein's activity is tightly regulated by lin-4, a microRNA which inhibits LIN-14 protein synthesis through complementary base pairing with sequences in the lin-14 mRNA 3' untranslated region.