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Paul W. Sternberg is an American biologist. He does research for WormBase on C. elegans , a model organism.
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Paul W. Sternberg is an American biologist. He does research for WormBase on C. elegans , a model organism.
Paul Sternberg grew up in Long Island, New York. He attended Hampshire College for undergrad in Amherst, Massachusetts where he got a B.A. in 1978. After that he went to MIT where he received his PhD in Biology for work on nematode development with Robert Horvitz. He went on to do postdoctoral research with Ira Herskowitz in yeast molecular development at the University of California San Francisco. [1] He is currently working at the California Institute of Technology as the Thomas Hunt Morgan Professor of Biology. [2]
Sternberg is a Primary investigator for WormBase. WormBase is a data repository for nematode biology. C. elegans has been used in studies of development and neurobiology. WormBase has information from nine species and five are from the genus Caenorhabditis , one of which is C. elegans. WormBase provides: a genome browser, genome, gene and protein sets for searches on sequence similarities and gene and protein summaries. [3]
He also serves as a primary investigator for the Gene Ontology Consortium. The consortium provides knowledge on the functions of genes and gene products. It was founded in 1998 and is widely accepted in the life sciences. The Gene Ontology resource has the most comprehensive information about the functions of genes. [4] ”The ontology covers three distinct aspects of gene function: molecular function, cellular component, and biological process”. [4]
Sternberg is a coauthor on the article, "Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans" (2019). They used C. elegans as a genetic model to look for phenotypic missense alleles collected from autism spectrum disorder studies done in humans. Missense variants cause around half the genetic changes that are known to cause disease. They used CRISPR-Cas9 to generate C. elegans equivalent human missense mutants. They compared the phenotypes from the missense mutants to the wildtype and known loss-of-function mutant controls in the autism-associated missense alleles. They found that 70% of missense alleles showed evident phenotypic changes in locomotion, morphology, and fecundity. They used this method to show subtle phenotypic changes and the effect that missense mutations can have on human disease. They did find that 14 missense variants have a significant function in C. elegans orthologs of human genes. [5]
"Gonadal cell lineages of the nematode Panagrellus redivivus and implications for evolution by the modification of cell lineage"(1981) Sternberg and Horvitz compared the gonadal cell lineages of Panagrellus redivivus to the gonadal lineages of C.elegans. They found that the death of Z4.pp is what probably prevents the posterior ovary in P. redivivus from developing which in C. elegans controls the development of that posterior ovary. This is thought to be the reason why there is a gross difference in the morphology of the P.redivivus female gonads and the C.elegans hermaphrodite. [6]
"Postembryonic nongonadal cell lineages of the nematode Panagrellus redivivus: Description and comparison with those of Caenorhabditis elegans" (1982) Horvitz and Sternberg looked at the postembryonic nongonodal cell lineages of P.redivivus and compared it to C.elegans. They found minor differences in the two cell lineages and found that the differences are because of two types of evolutionary changes. [7]
“Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans"(1983) In this publication they found 19 genes in C. elegans that affected neural cell fate and cell lineages during development. Mutations in genes lin-22, lin-12, unc-86, and ced-3 can cause specific transformations in the fate of particular cells. They found that these genes and others may act in a hierarchy to affect decisions at different stages within cell lineages. They found that unc-86 can affect non neural aspects of development even though it is specific for neural lineages. [8]
"Multiple functions of let-23, a caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction”(1991) Let-23 gene has many different functions during C.elegans development. Aroian and Sternberg found that let-23 function is necessary for vulval precursor cells to answer the signal responsible for vulval differentiation. The let-23 receptor tyrosine kinase controls two opposing pathways. One pathway is responsible for stimulating vulval differentiation and the other prevents vuval differentiation. They also discovered that let-23 kinase function in at least 5 different tissues. [9]
“The lin-15 locus encodes two negative regulators of caenorhabditis elegans vulval development.”(1994) lin-15 is a negative regulator of vuval differentiation. Huang, Tzou, and Sternberg discovered that lin-15 encodes 2 transcripts that do not overlap and are transcribed in the same direction. They were able to analyze what role lin-15 plays in the signaling pathway and found that lin-15 acts upstream and parallel to the inductive signal of let-23. [10]
“A gonad-derived survival signal for vulval precursor cells in two nematode species”(1998) Felix and Sternberg discovered that there is a survival signal that prevents cell death in vulval precursor cells in T.aceti and Halicephalobus sp. Ablation of the gonads in these two nematodes causes vulval precursor cell death. This is opposite of what is seen in C.elegans and many other nematode species typically if there is ablation of the gonads the vulval precursor cells default to an epidermal fate and do not undergo programmed cell death. [11]
“Evidence of a mate-finding cue in the hermaphrodite nematode Caenorhabditis elegans”(2002) Simon and Sternberg performed several different assays and found that males specifically, respond to a sexually dimorphic cue that hermaphrodites gives off. They found that the cue is not discharged from vulva tissue. The cue is likely detected by a chemosensory organ in the male. Their findings demonstrated that males do have a preference in mate selection and hermaphrodites do play a role in mating. [12]
“An imaging system for standardized quantitative analysis of C. elegans behavior”(2004) Sternberg et al., created a widely available quantitative method to evaluate behavioral phenotypes. They were able to record behavior at high magnification, over long periods of time, and quantify behaviorally relevant features for later analysis. This makes it possible to easily compare data from different labs by standardizing behavioral assays. It would also allow the recording of individual nematodes and quantify 144 specific phenotype parameters. [13]
Below are some of Sternberg's most-cited publications:
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.
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".
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.
An equivalence group is a set of unspecified cells that have the same developmental potential or ability to adopt various fates. Our current understanding suggests that equivalence groups are limited to cells of the same ancestry, also known as sibling cells. Often, cells of an equivalence group adopt different fates from one another.
Caenorhabditis briggsae is a small nematode, closely related to Caenorhabditis elegans. The differences between the two species are subtle. The male tail in C. briggsae has a slightly different morphology from C. elegans. Other differences include changes in vulval precursor competence and the placement of the excretory duct opening. C. briggsae is frequently used to study the differences between it and the more intimately understood C. elegans, especially at the DNA and protein sequence level. Several mutant strains of C. briggsae have also been isolated that facilitate genetic analysis of this organism. C. briggsae, like C. elegans, is a hermaphrodite. The genome sequence for C. briggsae was determined in 2003.
Caenorhabditis is a genus of nematodes which live in bacteria-rich environments like compost piles, decaying dead animals and rotting fruit. The name comes from Greek: caeno- ; rhabditis = rod-like.
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.
The anchor cell is a cell in nematodes such as Caenorhabditis elegans. It is important in the development of the reproductive system, as it is required for the production of the tube of cells that allows embryos to pass from the uterus through the vulva to the outside of the worm.
The Caenorhabditis eleganssel-12 gene encodes a multi-pass transmembrane domain protein that is similar to human presenilin. sel-12 positively regulates the lin-12 and glp-1 Notch signaling pathways during hermaphrodite gonadal, vulval, and germline development. sel-12 also plays a role in thermotaxis.
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.
DAF-16 is the sole ortholog of the FOXO family of transcription factors in the nematode Caenorhabditis elegans. It is responsible for activating genes involved in longevity, lipogenesis, heat shock survival and oxidative stress responses. It also protects C.elegans during food deprivation, causing it to transform into a hibernation - like state, known as a Dauer. DAF-16 is notable for being the primary transcription factor required for the profound lifespan extension observed upon mutation of the insulin-like receptor DAF-2. The gene has played a large role in research into longevity and the insulin signalling pathway as it is located in C. elegans, a successful ageing model organism.
mir-48 microRNA is a microRNA which is found in nematodes, in which it controls developmental timing. It acts in the heterochronic pathway, where it controls the timing of cell fate decisions in the vulva and hypodermis during larval development.
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.
Cell lineage denotes the developmental history of a tissue or organ from the fertilized egg. 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.
Caenorhabditis tropicalis is a species of Caenorhabditis nematodes, belonging to the Elegans super-group and Elegans group within the genus. It is a close relative of C. wallacei.C. tropicalis is collected frequently in tropical South America, Caribbean islands, and various islands in the Indian and Pacific Oceans from rotting fruit, flowers and stems. C. tropicalis was referred to as "C. sp. 11" prior to 2014.
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.
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.
The age-1 gene is located on chromosome 2 in C.elegans. It gained attention in 1983 for its ability to induce long-lived C. elegans mutants. The age-1 mutant, first identified by Michael Klass, was reported to extend mean lifespan by over 50% at 25 °C when compared to the wild type worm (N2) in 1987 by Johnson et al. Development, metabolism, lifespan, among other processes have been associated with age-1 expression. The age-1 gene is known to share a genetic pathway with daf-2 gene that regulates lifespan in worms. Additionally, both age-1 and daf-2 mutants are dependent on daf-16 and daf-18 genes to promote lifespan extension.
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