Maartens A (2018) Development "An interview with Susan Strome."

Maartens A

[Development, 2018]

Susan Strome is Distinguished Professor of Molecular, Cell and Developmental Biology at the University of California, Santa Cruz, USA. Recently appointed an editor at Development, her lab studies the regulation of germ cell development in<i>C. elegans</i>, with a particular focus on the epigenetic transmission of chromatin states. We caught up with Susan to discuss her early career switch from prokaryotes to worms, her experiences of small and big science, and why teaching is so important to her.

Ailion, Michael et al. (2009) International Worm Meeting "Identification of a novel dense-core vesicle trafficking pathway."

Ailion, Michael, Schuske, Kim, Dalton, Susan, Pappas, Andrea, Jorgensen, Erik, Hullett, Patrick

[International Worm Meeting, 2009]

In C. elegans, the heterotrimeric Ga subunit Gq is a positive regulator of neurotransmission. By screening for genetic suppressors of an activated Gq mutant, we identified 10 genes that appear to regulate dense-core vesicle trafficking or release. Two of the genes, unc-31(CAPS) and pkc-1 (a protein kinase C isoform), have been previously shown to be required for dense-core vesicle docking and release. In unc-31 and pkc-1 mutants, fluorescently tagged peptides are transported to their normal release sites in the dorsal nerve cord but have reduced release. In the other eight mutants, there is reduced transport of tagged peptides to the dorsal cord, indicating that these genes function in an earlier step of dense-core vesicle biogenesis or trafficking. One of the mutants carries a mutation in a splice site of the kinesin unc-104 and has a movement phenotype unlike other unc-104 mutants. The other 7 mutants have an unmotivated movement phenotype; they are capable of coordinated movement when stimulated, but show little spontaneous movement on food. Thus, these genes appear to function in the regulation of movement rather than the execution of coordinated movements. One of the unmotivated genes, rund-1, encodes a novel conserved protein with a putative small GTPase effector domain (the RUN domain). We also found that mutants in the small GTPase rab-2 have phenotypes very similar to rund-1 mutants. Genetic epistasis data suggest that rab-2 and rund-1 act in the same pathway. rund-1 is highly expressed in neurons and neuronal specific expression rescues the movement defect. In neurons, RUND-1::GFP is concentrated in punctate positions in the cell body that may represent some secretory compartment. RUND-1::GFP does not colocalize with ER or Golgi markers though it appears to be immediately adjacent to the Golgi marker mannosidase II. We have also molecularly identified three other genes in this pathway. All three encode novel conserved proteins that act genetically in the same pathway with rab-2 and rund-1 and cause similar peptide trafficking defects. These include two novel proteins, one with coiled-coil domains and one with WD40 domains, and hid-1, a previously cloned mutant with phenotypes consistent with defects in dense-core vesicle secretion. All three are expressed throughout the nervous system. Thus, these genes define a conserved pathway that regulates dense-core vesicle trafficking in neurons.

Harris HE et al. (1977) Cell "Myosin and paramyosin of Caenorhabditis elegans: biochemical and structural properties of wild-type and mutant proteins."

Epstein HF, Harris HE

[Cell, 1977]

Myosin and paramyosin have been purified from the nematode, Caenorhabditis elegans. The properties of the myosin in general resemble those of other myosins. The native molecule is a dimer of heavy (210,000 dalton) polypeptide chains and contains 18,000 and 16,000 dalton light chains. When rapidly precipitated from solution, it forms small, bipolar aggregates, about 150 nm long, consistent with the expected molecular structure of a rigid rod with a globular head region at one end. Its ATPase activity is stimulated by Ca2+ and EDTA. The myosin binds to F actin in a polar and ATP-sensitive manner, and the Mg2+-ATPase is activated by either F actin or nematode thin filaments. Dialysis of myosin to low ionic strength produces very long filaments. When a myosin-paramyosin mixture is dialyzed under the same conditions, co-filaments form which consist of a myosin cortex, surrounding a paramyosin core. Some properties of myosins from the mutants E675 and E190, which have functionally and structurally altered body wall muscles, are compared with those of wild-type myosin. These myosins behave normally in in vitro tests. The implications of these results are discussed in terms of the myosin heavy chain composition.

Gasser SM (2022) Epigenomics "Lessons in chromatin organization and gender equity in research: an interview with Susan Gasser."

Gasser SM

[Epigenomics, 2022]

In this interview, Professor Susan Gasser speaks with Storm Johnson, commissioning editor for <i>Epigenomics</i>, on her research on genome stability, epigenetic regulation and chromatin organization, as well as her work supporting women in research. Susan Gasser completed her BA at the University of Chicago, with an honors thesis in biophysics, and her PhD in biochemistry at the University of Basel in 1982, with Gottfried Schatz. She was a postdoc with Ulrich Laemmli at the University of Geneva, which initiated her career-long interest in chromosomes and chromatin structure. She established her own laboratory at the Swiss Institute for Experimental Cancer Research (ISREC) in 1986, focusing on chromatin organization in budding yeast, combining genetics, microscopy and biochemical approaches to understanding silent chromatin and telomeres. In 2001, she was named professor of molecular biology at the University of Geneva and expanded her laboratory's pioneering use of high-resolution time-lapse fluorescence microscopy to study single locus dynamics in the nucleus. From 2004 to 2019, Susan was the Director of the Friedrich Miescher Institute for Biomedical Research in Basel, where she also led a research group until the end of 2020. In Basel, she extended her research interests into heterochromatin in <i>Caenorhabditiselegans</i>. Her laboratory identified the mechanisms that position tissue-specific genesin the nuclei ofembryos and ofdifferentiated tissues, combining high throughput molecular analyses with cell biology to determine structure-function relationships in chromatin. Since January 2021, Susan Gasser has been <i>professor invite</i> at the University of Lausanne and Director of the ISREC Foundation, where she is helping shape the new Agora Institute of Translational Cancer Research. She was elected to the Academie de France, Leopoldina, European Molecular Biology Organization (EMBO), American Association for the Advancement of Science and Swiss Academy of Medical Sciences, and she received the French National Institute of Health and Medical Research (INSERM) International Prize in 2011, the Federation of European Biochemical Societies | EMBO Women in Science Award in 2012, the Weizmann Institute Women in Science Award in 2013 and honorary doctorates from the University of Lausanne, the University of Fribourg and Charles University in Prague. In Switzerland, she was the recipient of the Friedrich Miescher Award, the National Latsis Prize and the Otto Naegeli Award for the promotion of medical research. She participates in numerous review boards and advisory committees in Switzerland, across Europe and in Japan; she currently serves on the governing board of the Swiss Federal Institutes of Technology and the Swiss Science Council. From 2000 to 2004, she was vice chairperson, then chairperson of the EMBO Council. Susan led the Gender Committee of the Swiss National Science Foundation from 2014 to 2019 and initiated the Swiss National Science FoundationPrima program for the Promotion of women in academia. She has actively promotedthe careers of women scientists in Europe and Japan.

Schachat FH et al. (1977) Cell "Two homogeneous myosins in body-wall muscle of Caenorhabditis elegans."

Harris HE, Schachat FH, Epstein HF

[Cell, 1977]

Myosin purified from the body-wall muscle-defective mutant E675 of the nematode, Caenorhabditis elegans, has heavy chain polypeptides which can be distinguished on the basis of molecular weight. On SDS-polyacrylamide gels, bands are found at 210,000 and 203,000 daltons. This is in contrast to myosin from the wild-type, N2, which has a single heavy chain band at 210,000 daltons. Both heavy chains of E675 are found in body-wall muscle. When native myosin from E675 is fractionated on hydroxyapatite, it is separated into myosin containing predominantly one or the other molecular weight heavy chain and myosin containing a mixture of the heavy chains. Comparison of the CNBr fragments of myosin that contains predominantly 210,000 dalton heavy chains with those that contains predominantly 203,000 dalton heavy chains reveals multiple differences. These differences are not explained by the difference in molecular weight of the heavy chains, but may be explained if each type of heavy chain is the product of a different structural gene. Furthermore, because there are fractions which exhibit >80% 210,000 or >80% 203,000 dalton heavy chain, there is myosin which is homogeneous for each of the heavy chains. Although N2 myosin has only a single molecular weight heavy chain, it too is fractionated by hydroxyapatite. By comparing the CNBr fragments of different myosin fractions, we show that N2, like E675, has two kinds of heavy chains. E190, a body-wall muscle-defective mutant in the same complementation group as E675, is lacking the myosin heavy chain affected by the e675 mutation. This property has allowed us to determine by co-purification of labeled E190 myosin in the presence of excess, unlabeled E675 myosin that most, if not all, of the myosin that contains two different molecular weight heavy chains is due to the formation of complexes between homogeneous myosins and not to a heterogeneous myosin.

Spieth J et al. (1984) Worm Breeder's Gazette "the yolk protein gene family of C elegans: YP6, the gene for the precursor to yp115 and yp88."

Blumenthal TE, Spieth J

[Worm Breeder's Gazette, 1984]

Four yolk proteins have been identified in C. elegans: Two closely related proteins of approximately 170,000 daltons (yp170A and yp170B), and two other polypeptides of 115,000 daltons (yp115) and 88,000 daltons (yp88) (Sharrock, 1983. Develo. Biol, 96, 182-188). yp115 and yp88 have been shown to be derived from a 180,000 dalton precursor ( Sharrock, 1984, J. Mol. Biol 174, 419-431). We recently have shown that yp170A and yp170B are encoded by a five gene family (YP1-5) ( Blumenthal et al.. 1984, J. Mol. Biol. 174, 1-18). We have now cloned a developmentally-regulated gene that, based on the timing of expression, size and abundance of the mRNA and finally, hybrid-arreat translation experiments, encodes the 180.000 dalton precursor to yp115 and yp88 . The gene (YP6) was cloned from a C. rary by selecting abundantly expressed sequences that were adult specific but did not hybridize to YP1-5. Genomic clones were selected from John Karn's lambda1059 library. Based on genomic Southern blots the precursor to yp115 and yp88 is encoded by a single-copy gene. It is about 5.5 kb long and hybridizes to a 5.2 kb RNA. YP6 RNA is as abundant in adult hermaphrodites as is the RNA from the YP1-5 gene family but, like YP1-5 RNA, YP6 RNA is not detectable in larvae or adult males. Based on DNA sequence comparison YP6 is distantly related to the YP1- 5 genes suggesting that all of the yolk protein genes evolved from a common ancestor.

Mango S (2009) Curr Biol "Q&A: Susan Mango."

Mango S

[Curr Biol, 2009]

Susan Mango is Benning Professor of Oncological Sciences at the University of Utah and an Investigator at the Huntsman Cancer Institute. She grew up in England and Washington D.C. before attending Harvard University. She received her Ph.D. from Princeton, where she studied the c-myc oncogene with Michael Cole. She was introduced to the nematode Caenorhabditis elegans as a postdoc with Judith Kimble at the University of Wisconsin - Madison, and moved to Utah in 1996 to start her own lab. After 13 years at the University of Utah, she will move to Harvard University in July 2009. Her principal focus is transcriptional strategies of organ development, using the C. elegans foregut as a model.

Sharrock WJ (1983) Dev Biol "Yolk proteins of Caenorhabditis elegans."

Sharrock WJ

[Dev Biol, 1983]

A group of proteins judged on several criteria to be yolk proteins have been isolated from a homogenate of the nematode Caenorhabditis elegans. Comparison of partial proteolysis fragments indicates that the two bands of a 170,000-dalton doublet (yp170) are closely related; bands observed at 115,000 daltons (yp115) and 88,000 daltons (yp88) appear to be structurally distinct. All three yolk protein species are glycoproteins, as judged by binding of the lectin concanavalin A. The yp170 doublet has been purified by gel filtration in the presence of sodium dodecyl sulfate. An antiserum obtained by immunization with the purified yp170 doublet does not bind either of the two smaller proteins. Staining of C. elegans eggs by indirect immunofluorescence with the anti-yp170 serum indicates a dispersed cytoplasmic location for the antigen throughout embryogenesis, with apparent segregation to the intestine immediately prior to hatching.

Warnhoff, Kurt et al. (2021) International Worm Meeting "Interkingdom transfer of molybdenum cofactor from bacteria to C. elegans"

Hercher, Thomas, Warnhoff, Kurt, Ruvkun, Gary, Mendel, Ralf

[International Worm Meeting, 2021]

The molybdenum cofactor (Moco) is a 520 dalton prosthetic group that is synthesized in a multi-step enzymatic pathway present in Archaea, Bacteria, and Eukarya. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco-biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy, however free Moco is too fragile to be purified and administered therapeutically. Surprisingly, Moco biosynthesis is not essential in the nematode Caenorhabditis elegans if they are fed bacteria that synthesize Moco. Our genetic and biochemical studies demonstrate that protein-bound Moco is the stable, bioavailable species of Moco taken up by C. elegans from bacteria and is an effective dietary supplement in a C. elegans model of Moco deficiency. These findings establish an animal pathway for Moco transport and suggest a novel therapeutic strategy for Moco deficiency.

Russnak RH et al. (1983) Nucleic Acids Res "Cloning and analysis of cDNA sequences coding for two 16 kilodalton heat shock proteins (hsps) in Caenorhabditis elegans: homology with the small hsps of Drosophila."

Candido EPM, Russnak RH, Jones D

[Nucleic Acids Res, 1983]

The nucleotide sequences of two different cDNAs, CEHS48 and CEHS41, coding for the 16,000 dalton heat shock proteins (hsps) of Caenorhabditis elegans have been determined. CEHS48 codes for a polypeptide of 135 amino acids, approximately 15 fewer than the complete protein while CEHS41 is missing approximately 46 amino acids. From nucleotide 113 to the TAA termination signal the extent of homology between the sequences is 91%. Toward the 5' ends, the homology drops to 20% and results in completely divergent amino acid sequences. The 3' noncoding regions are only 30% homologous. Only CEHS48 contains a poly(A) signal and a poly(A) tail, suggesting that CEHS41 has an incomplete 3' end. The region from amino acid 43 to amino acid 115 shows extensive homology with corresponding regions in the four small hsps of Drosophila melanogaster and in mammalian alpha- crystallin. Two-dimensional gel analysis of in vitro synthesized hsp16 reveals the existence of five distinct components of identical molecular weights, but with different isoelectric points.